CN1241193A - Meningococcus vaccine comprising valence of BZ23 strain - Google Patents
Meningococcus vaccine comprising valence of BZ23 strain Download PDFInfo
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- CN1241193A CN1241193A CN98801479A CN98801479A CN1241193A CN 1241193 A CN1241193 A CN 1241193A CN 98801479 A CN98801479 A CN 98801479A CN 98801479 A CN98801479 A CN 98801479A CN 1241193 A CN1241193 A CN 1241193A
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- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- IUAYMJGZBVDSGL-XNNAEKOYSA-N gramicidin S Chemical compound C([C@@H]1C(=O)N2CCC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CCCN)C(=O)N[C@H](C(N[C@H](CC=2C=CC=CC=2)C(=O)N2CCC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CCCN)C(=O)N[C@@H](CC(C)C)C(=O)N1)C(C)C)=O)CC(C)C)C(C)C)C1=CC=CC=C1 IUAYMJGZBVDSGL-XNNAEKOYSA-N 0.000 description 1
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- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 description 1
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- 238000005259 measurement Methods 0.000 description 1
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- 229950006238 nadide Drugs 0.000 description 1
- LYRFLYHAGKPMFH-UHFFFAOYSA-N octadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(N)=O LYRFLYHAGKPMFH-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
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- 108010073101 phenylalanylleucine Proteins 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
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- 229920000768 polyamine Polymers 0.000 description 1
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/22—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Neisseriaceae (F)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Oncology (AREA)
- Neurosurgery (AREA)
- Gastroenterology & Hepatology (AREA)
- Communicable Diseases (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
The invention concerns a pharmaceutical composition comprising (i) the subunit of least molecular weight TbpB of the human transferrin receptor (HTR) of a Neisseria meningitis strain having a DNA sequence coding for TbpB, (a) which contains two AvaII restriction sites, 3 HincII restriction sites, no VspI restriction site and no XhoI restriction site or (b) from which it is possible to generate by PCR (polymerase chain reaction) using primers P3 of formula 5'-AAGACCAAGGCGGATACGGTTTTGC-3' and P4 of formula 5'-GAAGACGAGTCGGAAACAAAGGGATG-3', a polynucleotide of 765 to 775 nucleotides. Such a strain is for example the BZ83 strain whereof the DNA sequence coding for TbpB is shown in the SEQ ID NO 1.
Description
The present invention relates to be used for the treatment of or prevent meningococcal infection new pharmaceutical composition, said composition contains meningitis naphthalene Se Shi coccus bacterial strain ET-5 complex body, TbpB (Tbp2) subunit of the human transferrin acceptor (HTR) of BZ83 flora.
Generally speaking, meningitis is viral source or bacterial origin.Main morbific bacterium is meningitis naphthalene Se Shi coccus and Haemophilus influenzae, and they relate separately to about 40 and 50% bacterium meningitis patient.
Meningitic record in French meningitis naphthalene Se Shi coccus is annual about 600-800 patient.In the U.S., annual patient's number is about 2500 to 3000.
Characteristic meningitis naphthalene Se Shi coccus kind according to capsular polysaccharide is divided into serogroups by the Asia.Though have about 12 kinds of serogroupss, 90% meningitis patient is owing to 3 kinds of serogroups: A, B and C.
Existence based on the effective vaccine of capsular polysaccharide can stop the meningitis that causes by meningitis naphthalene Se Shi coccus serogroups A and C.These polysaccharide do not have for the children below 2 years old or less demonstration immunogenicity and not induction of immunity memory.But these shortcomings can overcome by these polysaccharide are combined with carrier proteins.
On the contrary, whether no matter be combining form, the polysaccharide of meningitis naphthalene Se Shi coccus B flora does not have for the people or does not almost show immunogenicity.Therefore, special wish to find anti-by the meningitic vaccine of meningitis naphthalene Se Shi coccus inductive, particularly based on the vaccine of serogroup B rather than polysaccharide.
For this reason, someone's adventitia of proposing meningitis naphthalene Se Shi coccus has different protein.Aspect this, cause special concern for the acceptor of people's transferrin.
Generally speaking, the growth needs iron of most bacterium, and they have grown the specific system that obtains this metal.Particularly for meningitis naphthalene Se Shi coccus, it is people's a strict pathogenic agent, only for example transferrin and lactoferrin obtain iron from the defeated protein of people's Railway transportation, because the amount of the iron of free form is inappreciable (for the rank of 10-18M) in human body, in any case be not enough to allow the growth of bacterium.
Therefore, meningitis naphthalene Se Shi coccus has the acceptor of human transferrin and the acceptor of human lactoferrin, enables to fix these iron chelating protein and after this absorbs its needed iron of growing.
The human transferrin acceptor of meningitis naphthalene Se Shi coccus bacterial strain B16B6 is by people such as Schryvers purifying (WO90/12591) from the film extract.This protein that it is believed that purifying is gone up substantially by 2 types polypeptide and is formed: have the polypeptide of high apparent molecular weight (100 kilodalton) and have the polypeptide of low apparent molecular weight (about 70 kilodaltons), see as pass through polyacrylamide gel electrophoresis in the presence of SDS after.
For the needs of present patent application, particularly be referred to as human transferrin acceptor (HTR) and constitute its polypeptide as subunit through random definition by the product of people's purifying such as Schryvers.In the article below, the subunit of high molecular and lower molecular weight is referred to as TbpA (Tbp1) and TbpB (Tbp2) respectively.
Since people's such as Schryvers research in advance, had been found that meningitis naphthalene Se Shi coccus kind is divided into different 2 the bacterial strain types (WO93/6861 and WO93/7172) of corresponding HTRs structure basically.The bacterial strain that is referred to as first type of M982 (or IM2169) has the antiserum(antisera) reaction with the HTR of anti-M982 bacterial strain, but with the nonreactive TbpB of antiserum(antisera) of the HTR of anti-B16B6 (or IM2394) bacterial strain; And another type that is referred to as B16B6 has the antiserum(antisera) reaction with the HTR of anti-B16B6 (or IM2394) bacterial strain, but with the nonreactive TbpB of antiserum(antisera) of the HTR of anti-M982 bacterial strain.Therefore there is antigenic difference in the level in the subunit of lower molecular weight.But this difference is limited because with people such as Griffiths, it is opposite that FEMS microorganism communication (1990) 69:31 proposes, and is lowered to 2 main types.
For example type M982 bacterial strain is the M982 bacterial strain, has described the sequence of this bacterial strain tbpB gene and be Z15130 with reference to registration number in the EMBL database in patent application EPA586266; Bacterial strain 6940, M978 and S3032 have the sequence of (sic) 5 ' tbpB gene to be described at WO95/33049; The sequence of bacterial strain BZ83 and 8680 tbpB gene is described at WO95/33049 and WO97/13860 respectively; (these sequences also are present in the EMBL database, corresponding registration number Z50732 and Y09977); Or also having bacterial strain 32/94 and 8710 its sequences to be present in the EMBL database, corresponding registration number is Y09617 and Y09618.These bacterial strains and other bacterial strain can from Nat Public Health Inst of Norway Oslo, the meningococcus preservation center of world health organization's cooperation, doctor Caugant locates to obtain (referring to the Ph D dissertation that the Claude Bernard university-lyonI that is submitted to by Bachra Rokbi October 10 nineteen ninety-five submits to before, name is called " Etude de la variabilit é antig é niqueet mol ě culaire du r é cepteur de la transf é rrine humainne de N.meningitidis " (research that the antigenicity of the human transferrin acceptor of meningitis naphthalene Se Shi coccus and blocking agent change)).The characteristic of bacterial strain is provided in the following Table IV.The sequence description of the DNA of the TbpB of coding B16B6 bacterial strain is in EPA586266.
The research of dna fragmentation of each TbpBs of encoding has shown according to the type of its origin is segmental and has varied in size.This may change the definition to M982 and B16B6 type that is provided by WO93/6861 at first.Size definition bacterial strain type according to the TbpB gene is suitable at present: be about 1.8 kilobase for the about 2.1-2.3 kilobase of TbpB of type M982 with for the TbpB of type B 16B6.
Protein TbpB, rather than Tbp1 has the numerous characteristics that can become the potential candidate vaccine: general expression, and the entering on the microorganism surface is induced the ability of bacteriocidin and limited mutability, because as already explained, identified two main floras at present.
By means of this discovery, the someone has advised pharmaceutical composition, and it contains:
(i) HTR (WO93/6861) of at least one bacterial strain of the HTR of at least one bacterial strain of B16B6 type and M982 type; Or
The (ii) TbpB (WO93/7172) of at least one bacterial strain of the TbpB of at least one bacterial strain of B16B6 type or M982 type.
Worldwide collection causes meningitis patient's bacterial strain (independent or popular case), divides to its research and based on various standards.Widely used first method is respectively based on the capsular polysaccharide level, and the outer membrane protein of 2/3 type is divided into serogroups with meningococcus, serotype or blood serum subtype with the antigenic different of 1 type outer membrane protein.This classification is carried out by means of monoclonal antibody.For example, M982 is divided into serogroup B with bacterial strain, serotype 9, inferior serotype P1.9 (B:9:P1.9).
Another international sorting technique is based on the electrophoretic mobility of some metabolic enzyme.This is MLEE (a multidigit point electrophoresis enzyme), by people such as Olyhoek, and " naphthalene Se Shi coccus pathogenic agent ", (1985), SchoolnickG.K. (AAM): 530; People such as Caugant, microorganism hereditary magazine (1986) 132:641; People such as Selander, environmental microorganism is used (1986) 51:873; People such as Caugant, genetics (1981) 98:464; People such as Caugant, PNAS (1986) 83:4931 has described the purposes of this enzyme.Generally speaking, 15 enzymes below having analyzed: malic enzyme (MAE), glucose-6-phosphate dehydrogenase (G6PD) (G6P), peptase (PEP), isocitric enzyme (IDH), depend on the glutamate dehydrogenase (GD1 and GD2) of nicotinamide adenine dinucleotide phosphate (NADP) (NAD), alcoholdehydrogenase (ADH), FURAMIC ACID (FUM), alkaline phosphatase (ALK), indophenol oxidase (IP1 and IP2), Myokinase (ADK) and desaturase (UDH).The electrophoresis form (or heteroenzyme) of various enzymes is corresponding to the allelotrope of similar genetic locus.The allelic specificity of these 15 kinds of enzymes is in conjunction with having constituted a kind of electrophoresis type (ET).These types can be divided into family or complex body (group).For example, the ET-5 complex body is made up of 22 electrophoresis types that very closely connect (greatest genetic distance .16).In the table below, indicated the allele distributions (having indicated the allelotrope number at each seat) of the bacterial strain of EF-5 electrophoresis type for each of 15 kinds of enzymes.The enzyme (G6P and UDH) of indicating its allelotrope (one or more) in the ET-5 complex body, to change at black matrix.
Table 1
| Enzyme | MAE | ?G6P | ?PEP | IDH | ?ACO | GD1 | GD2 | ADH | ?FUM | ??ALK | ??IP1 | ??IP2 | ??ADK | ??UDH |
| Allelotrope | ??1 | ??1 | ??7 | ??8 | ??4 | ?2 | ??3 | ?2 | ???1 | ??1 | ???2 | ???3 | ????2 | ???3 |
In pedigree, there are various close electrophoresis complex body or types.Up to the present,, in transmissible disease magazine (1990) 162:867, describe, defined 10 pedigrees (I is to X) of one group that at least 5 close mutually electrophoresis types of each representative are formed for example as people such as Caugant.For example, pedigree III is with ET type 24, and 24.1-4 and 25 organizes into groups again.
In in the past 25 years, had been found that the bacterial strain that causes a large amount of in the world meningitis patient (U.S. (Oregon, the State of Washington) for example, Norway, Cuba, Chile, Brazilian and Dutch, New Zealand) belongs to the ET-5 complex body or belongs to the III pedigree.Therefore, provide the vaccine that contains the TbpB that antigen for example obtains from this complex body bacterial strain to become needs very soon.In fact, just in TbpB (referring to the WO97/13860) scope that obtains from 8680 bacterial strains, in known various vaccine compositions like this.This bacterial strain belongs to the ET-5 complex body really.
But, have been found that now the clinical separation strain that belongs to the ET-5 complex body shows certain mutability at the tbpB gene level.Study causing epiphytotics 31 strain isolateds of nearest world's meningitis.Following aspect to the tbpB gene is analyzed: (a) aspect utilizes primer P1 (SEQIDNO:9; P1 is Z15130 corresponding to 115 to 113 of the sequence of M982 tbpB gene as registration number in the EMBL library) and primer P2 (antisense; SEQIDNO:10; P2 is Z15130 corresponding to 2264 to 2244 positions of the sequence of M982 tbpB gene as registration number in the EMBL library) after the genomic dna amplification gene, analyze the enzyme AvaII of tbpB gene, HincII, the restriction map of VspI and XhoI; (b) on the other hand by means of primer P3 (SEQIDNO:11) and P4 (antisense; SEQIDNO:12) analyze from the segmental size of the PCR that comes from the tbpB gene (polymerase chain reaction) of genomic dna amplification.
Bacterial strain M982, the restriction map of BZ83 and 8680 tbpB gene is shown in following Table II.Should be noted that the M982 bacterial strain does not belong to the ET-5 complex body.But, it also it is studied because having reference role for all bacterial strains of the tbpB gene with 2.1 to 2.3 kilobase.
Table II
NC: do not have to use in the cutting Table III below these collection of illustrative plates of letter designation: Table III
For the following Table IV of the results are shown in of all bacterial strains:
| ????Ava?II | ????Vsp?I | ????Xho?I | ????Hinc?II | |
| ????M982 | ????NC | ????1311?nt ????769?nt | ????NC | ????1229?nt ????319?nt ????281?nt ????259?nt |
| ????BZ83 | ????1184?nt ????477?nt ????415?nt | ????NC | ????NC | ????1155?nt ????385?nt ????276?nt ????257?nt |
| ????8680 | ????1507?nt ????445?nt | ????1298?nt ????470?nt ????266?nt | ????1551?nt ????483?nt | ????1191?nt ????527?nt ????316?nt |
| ????Ava?II | ????Vsp?I | ????Xho?I | ????Hinc?II | |
| ????M982 | ????N | ????G | ????N | ????I |
| ????BZ83 | ????A | ????N | ????N | ????B |
| ????8680 | ????C | ????D | ????E | ????F |
Table IV
| Bacterial strain | Serogroups | Time | The source | PCR product size (nt) (α) | TbpB gene (b) is with following enzyme restriction map | |
| AvaII?VspI?XhoI?HincII | ||||||
| * | ????BZ83 ????BZ169 ????NG080 ????NG1/84 ????NGP355 ????NGPB24 ????NGPB37 ????32/94 ????44 ????52 ????G111/91 ????M359/91 ????MA-5850 ????281 ????8679 ????AO15 ????AO20 ????8680 ????8726 ????NG3/83 ????M982 ????NG144/82 ????58/94 ????92/94 ????504/91 ????M871 ????230/89 ????BB393 ????BB396 ????8694 ????8696 ????8710 | ????B：15：- ????B：15：P1.16 ????B：15：P1.16 ????B：15：P1.16 ????B：15：P1.15 ????B：15：P1.7，16 ????B：15：P1.7，16 ????B：15：P1.7，16 ????B：15：P1.7，16 ????B：15：P1.7，16 ????B：15：P1.3，15 ????B：15：P1.3，15 ????B：4：?P1.15 ????B：4：?P1.15 ????B：15：P1.3 ????B：4：?P1.12 ????B：4：?P1.15 ????B：15：P1.3 ????B：4：?P1.3 ????B：15：P1.16 ????B：9：?P1.9 ????B：15：P1.16 ????B：15：12.13a ????B：15：7.16 ????B：4：- ????B：15：P1.7，16 ????B：4：?P1.15 ????B：15：P1.3 ????B：15：P1.3 ????B：15：- ????B：15：P1.3 ????B：15：P1.3 | ????1984 ????1985 ????1981 ????1985 ????1975 ????1984 ????1987 ????1994 ????1993 ????1993 ????1991 ????1991 ????1985 ????1992 ????1987 ????1988 ????1989 ????1987 ????1987 ????1984 ????1982 ????1994 ????1994 ????1991 ????1992 ????1989 ????1986 ????1986 ????1987 ????1987 ????1987 | The Dutch Norway Norway Norway Norway Norway Norway Finland Finland Iceland Iceland Spain Spain Chile South Africa Argentinian Israel of South Africa Chilean Norway U.S. Norway Norway Norway Cuba Chile Chile Chile | ????772 ????772 ????772 ????772 ????772 ????772 ????772 ????772 ????772 ????772 ????772 ????772 ????772 ????772 ????772 ????772 ????772 ????805 ????805 ????805 ????844 ????844 ????844 ????844 ????844 ????844 ????844 ????844 ????844 ????844 ????844 ????832 | ??A????N????N????B ??A????N????N????B ??A????N????N????B ??A????N????N????B ??A????N????N????B ??A????N????N????B ??A????N????N????B ??A????N????N????B ??A????N????N????B ??A????N????N????B ??A????N????N????B ??A????N????N????B ??A????N????N????B ??A????N????N????B ??A????N????N????B ??A????N????N????B ??A????N????N????B ??C????D????E????F ??C????D????E????F ??C????D????E????F ??N????G????N????I ??N????G????N????H ??N????G????N????I ??N????G????N????I ??N????G????N????J ??N????G????N????F ??N????N????N????F ??N????N????N????F ??N????N????N????F ??N????N????N????F ??N????N????N????F ??N????N????N????G |
Asterisk is meant the bacterial strain M982 of the part that is not the ET-5 complex body.
(a) indicated segmental size is by means of primer P3 and the P4 fragment from the genomic dna amplification, when the whole sequence of this gene is to obtain (bacterial strain M982, BZ83 and 8680) that calculate with base the time or on 3% sepharose the migration back with from bacterial strain M982, BZ83 and the 8680 PCR fragment comparative measurements that produce.For the result that this research is succeedd, at first from (MHA Difco) goes up the bacterial strain of cultivating and extracts genomic dna at the Mueller-Hinton agar plate.Utilize quick guanidinium isothiocyanate method to extract DNA people such as (, using microbe communication (1989) 8:151) Pitcher.Containing the 200 micro-molar concentrations dCTP of (respectively), dGTP, dATP and dTTP (Pharmacia-LKB); Carry out the PCR reaction in the volume of 100 micro-molar concentrations of primer of each 0.2 micro-molar concentration and the Taq polysaccharase (Appligene) of 2.5U.(Biometra carries out according to following program in Trio-thermobloc): 95 ℃ of initial sex change 5 minutes, 25 circulations then at the DNA thermal cycler in amplification; Respectively comprise successive sex change (30 seconds, 95 ℃), the extension (1 minute, 72 ℃) of annealing (30 seconds, 58 ℃) and DNA chain.On 3% sepharose, measure the size of amplified fragments after the electrophoresis at amplified production.
(b) by means of primer P1 and P2 by the restriction map of PCR from the gene of genomic dna amplification; Letter A-G and N are meant that (H is corresponding to restriction map: 1230,320,270,210 and 80nt at the indicated restriction map of Table III; J is corresponding to restriction map: 1350,570 and 330nt).For the result that this research is succeedd, the method for describing according to above-mentioned (a) prepares the DNA of bacterial strain, increases under the condition below then: 25 circulations; Each circulation comprises the sex change (1 minute, 94 ℃) of DNA, annealing (2 minutes, 58 ℃) and extension (3 minutes, 72 ℃).Digest in four independent reactions and in the fragment of last each amplification of purifying of Qiaquick post (Qiagen) and with four kinds of enzymes according to the explanation for preparing merchant (NewEngland Biolabs).By electrophoresis separation limit digestion product on 2% sepharose.
Verified thus mutability above-mentioned is lowered into 3 main cohorts (referring to Table IV).Most important group contains 17 bacterial strains, comprises BZ83 bacterial strain (representing percentage ratio 54.8%).10 bacterial strains of a group have and are characterised in that to have the PCR fragment that is same as the segmental single size of PCR (844nt) that obtains with the M982 bacterial strain.Though M982 bacterial strain itself is not the part of this group, be described (will be noted that term M982 group is not meant identical implication with the M982 type) according to the name of M982 in this article because its size is identical.In these 10 bacterial strains, the restriction map of tbpB gene shows some heterology: gene AvaII of no use or cut with XhoI; For VspI, perhaps there is not restricted site, perhaps be meant G class limitations collection of illustrative plates; Restriction map that obtains with HincII even heterology more.As an example, then be a group of 3 bacterial strains, 8680 bacterial strains are wherein arranged.Though it is less that 8710 bacterial strains are characterised in that the PCR fragment and the characteristic fragment of the bacterial strain of M982 cohort are compared size, the restriction map of tbpb gene shows that really this bacterial strain and M982 cohort are alike.
Predictor for the classification that confirms the PCR-based clip types, with bacterial strain 32/94, the tbpB gene clone of 8726 and 8710 (above Table IV records), order-checking and utilize Infobiogen multi beam sequence comparison program (people such as Dessen, Bisance: " being used to estimate the French program of biomolecular sequence database " (1990) Cabios6:355) with this sequence and prototype bacterial strain NZ83, the sequence of M982 and 8680 tbpB gene compares.Comparative result is listed in the Table V hereinafter based on homology percentage ratio (identity property), has confirmed the definite of classification really by pcr analysis.Table V
| ???32/94 | ??8680 | ??8710 | ??8726 | ??BZ83 | ??M982 | |
| ??32/94 | ????100 | ??74 | ??77 | ????75 | ????99 | ????78 |
| ??8680 | ????- | ??100 | ??79 | ????90 | ????74 | ????75 |
| ??8710 | ????- | ???- | ??100 | ????80 | ????77 | ????86 |
| ??8726 | ????- | ???- | ???- | ????100 | ????76 | ????74 |
| ??BZ83 | ????- | ???- | ???- | ????- | ????100 | ????79 |
| ??M982 | ????- | ???- | ???- | ????- | ????- | ????100 |
The research of the analysis of the tbpB gene of relevant above-reported has been theme (people such as Rokbi, the immunologic clinical diagnosis in laboratory (in September, 1997) 4 (5): 522) of publication.
Since then, had been found that the bacterial strain that does not belong to the ET-5 complex body has the TbpB gene that its Restriction Enzyme collection of illustrative plates is same as the TbpB gene of BZ83 bacterial strain.Some of these bacterial strains belongs to the III pedigree; Bacterial strain is 90/94 bacterial strain (doctor's Caugant collection) for example.
Have big representativeness in the middle of the cohort that the prevailing disease in the zonal source that the selection representative of known strain isolated to be tested changes and hypothesis are described by the BZ83 bacterial strain, can affirm that the bacterial strain of this group is to preponderate in nearest prevailing disease.Comprise in vaccine that from group it is seemingly gratifying hereinafter to be referred to as the TbpB that the bacterial strain of BZ83 group obtains by BZ83 bacterial strain explanation.
Therefore, the present invention relates to pharmaceutical composition, it comprises that (i) has the subunit (TbpB) of lower molecular weight of human transferrin acceptor (HTR) of meningitis naphthalene Se Shi coccus bacterial strain of the dna sequence dna of coding TbpB, or the (ii) fragment of described TbpB, wherein the dna sequence dna (a) in (i) contains 2 AvaII restriction sites, 3 HincII restriction sites, do not have VspI restriction site and XhoI restriction site or, (b) primer P4 of being 5 '-GAAGACGAGTCGGAAACAAAGGGATG-3 ' by means of primer P3 and the general formula of general formula 5 '-AAGACCAAGGCGGATACGGTTTTGC-3 ' preferably, can produce 765 to 775 Nucleotide, the preferably polynucleotide of 772 Nucleotide (bacterial strain of BZ83 cohort) from this sequence by PCR (polymerase chain reaction).
" a kind of TbpB subunit of bacterial strain, perhaps derive come from or from meningitis naphthalene Se Shi coccus bacterial strain winner " obviously be meant the genetic drift that presents in universal significance; Be not limited to physical process in other words, but be the result of mental process.Therefore, this statement has covered for example TbpB that is for example produced by the reorganization approach in intestinal bacteria.
The meningitis naphthalene Se Shi coccus bacterial strain that can be used for the TbpB of the object of the invention from its acquisition preferably belongs to the ET-5 complex body or belongs to the bacterial strain of III pedigree.For example, the bacterial strain as the BZ83 cohort of the part of ET-5 complex body is 32/94 bacterial strain.Bacterial strain as the BZ83 cohort of the part of pedigree III is 90/94 bacterial strain.The sequence of the TbpB gene of these bacterial strains is shown in hereinafter the recognition sequence symbol.
According to embodiment preferred, the TbpB that mixes composition of the present invention is that the meningitis naphthalene Se Shi coccus bacterial strain from the dna sequence dna with coding TbpB obtains, described dna sequence dna shows by 1184,477 and the AvaII restriction map formed of 3 fragments of 415nt, and by 1155,385,276 and the HincII restriction map formed of 4 fragments of 257nt.Preferably this TbpB has the aminoacid sequence (BZ83 bacterial strain) that is shown in SEQIDNO:2.
Another kind of optionally method also can be used the fragment that obtains from the TbpB of adhoc bacterial strain.Method according to the WO95/33049 suggestion can be identified for vaccine purpose fragment.
No matter the source that WO95/33049 discloses bacterial strain is how, can show three main structural regions to the research of TbpB subunit, one of them has specificity at least.According to this definition, show as hereinafter Table VI, by indicating amino acid whose position, the boundary that different zones is included and by with reference to SEQIDNO; 4 and 8 numbering that shows, the fixedly zones of M982 TbpB and B16B6TbpB.
Table VI
| ????M982?TbpB | ????B16B6?TbpB | |
| N-stub area or first zone | ????1-345 | ????1-325 |
| Engaging zones or second zone | ????346-543 | ????326-442 |
| C-stub area or the 3rd zone | ????544-691 | ????443-579 |
This definition can be used for the TbpB of all M982 or B16B6 type equally, and after M982 or B16B6 type sequence and canonical sequence compared, they had maximum homology.Therefore, as an example, the position that the zone of the TbpB subunit of bacterial strain 8680 shows is as follows: first zone (1-334), second zone (335-530) and the 3rd zone (531-677).
Known N-stub area or first zone are all sidedly to the binding site of ferritin and be very may be laterally therefore, and the independent N-stub area of result has constituted can select to be used for for example composition of vaccine purpose.
In addition, the sequence of M982 and B16B6 TbpB arranged relatively to study with maximum homology shown in the engaging zones that proves M982 TbpB that four alterable heights parts (also are referred to as engaging zones, as situation about in above-mentioned table, occurring), and B16B6 TbpB does not have these parts.These alterable heights partly are present in the TbpB of all M982 types.B16B6 type bacterial strain does not have these parts.In the content below, " engaging zones of M982 type " is meant the engaging zones with four this alterable height parts.
Compare by the sequence with the TbpB of various M982 types, the mutability of also knowing engaging zones is greater than other two zones.Because as if engaging zones optional to the human transferrin combined function, but, infer that acting on to small part of this zone is to induce " shielding " mutability so that avoid bacterial strain by the immune system recognition of individuality, this individual immunity system can only be discerned another bacterial strain at last.
According to this hypothesis, the engaging zones of the bacterial strain of M982 type has constituted the subject matter in the preparation vaccine.Really, if these zones are immunodominant, during immunization, mainly anti-this district of institute's inductive antibody and as a result immunne response will be specific to the TbpB albumen of homologous strain.
Consider The above results and hypothesis, the someone is proposed to be used in vaccine purpose for example and the TbpB of M982 type that need not be complete, but this TbpB lacks their four alterable height parts at least, or another kind of optionally mode, lacks second and the 3rd zone.
Also can contain from the bacterial strain of M982 cohort or the TbpB that obtains by the bacterial strain of the cohorts (8680 cohort) of 8680 representatives according to composition of the present invention.
Therefore, composition of the present invention can comprise in addition (i) from meningitis naphthalene Se Shi coccus obtain as the part of ET-5 complex body and have first other TbpB of the dna sequence dna of coding TbpB, or the fragment of (ii) described first other TbpB, wherein the dna sequence dna (a) in (i) does not contain AvaII and XhoI restriction site, perhaps, (b) primer P4 of being 5 '-GAAGACGAGTCGGAAACAAAGGGATG-3 ' by means of primer P3 and the general formula of general formula 5 '-AAGACCAAGGCGGATACGGTTTTGC-3 ' preferably, can produce 840 to 850 Nucleotide, the preferably polynucleotide of 844 Nucleotide (bacterial strain of M982 cohort) from this sequence by PCR.
According to embodiment preferred, first other TbpB is that the meningitis naphthalene Se Shi coccus bacterial strain from the dna sequence dna with coding TbpB obtains, described dna sequence dna contains 1 VapI restriction site and 3 HincII restriction sites, preferably this TbpB is that meningitis naphthalene Se Shi coccus bacterial strain from dna sequence dna with coding TbpB obtains, described dna sequence dna shows by 1311 and the VapI restriction map formed of 2 fragments of 769nt and by 1129,319,281 and the HincII restriction map formed of 4 fragments of 259nt.
Pharmaceutical composition of the present invention also can comprise in addition (i) from meningitis naphthalene Se Shi coccus obtain as the part of ET-5 complex body and have second other TbpB of the dna sequence dna of coding TbpB, or the fragment of (ii) described second other TbpB, wherein the dna sequence dna (a) in (i) contains 1 AvaII restriction site and 2 VspI restriction sites, 2 Hinc II of 1 XhoI restriction site restriction site, perhaps, (b) primer P4 of being 5 '-GAAGACGAGTCGGAAACAAAGGGATG-3 ' by means of primer P3 and the general formula of general formula 5 '-AAGACCAAGGCGGATACGGTTTTGC-3 ' preferably, can produce 800 to 810 Nucleotide, the preferably polynucleotide of 805 Nucleotide (bacterial strains of 8680 cohorts) from this sequence by PCR.
According to embodiment preferred, second other TbpB is that the meningitis naphthalene Se Shi coccus bacterial strain from the dna sequence dna with coding TbpB obtains, described dna sequence dna shows by 1507 and the AvaII restriction map formed of 2 fragments of 445nt, by 1298,470 and the VspI restriction map formed of 3 fragments of 266nt and by 1551 and the XhoI restriction map formed of 2 fragments of 483nt, with by 1191,527 and the HincII restriction map formed of 3 fragments of 316nt.Preferably, this second other TbpB has the aminoacid sequence (8680 bacterial strain) that is shown in SEQIDNO:6.
Except the TbpB that obtains from the ET-5 complex body, composition of the present invention also can contain one or more TbpB that obtain from the bacterial strain of other electrophoresis complex body.Particularly, imagination adds the TbpB of the bacterial strain of (i) M982 type, in other words, homology (identity property) degree with the bacterial strain of gene of about TbpB of 2.1 to 2.3kb and it and M982 TbpB is higher than by with the TbpB of the bacterial strain of ET-5 complex body and result's (homology of amino acid levels sequence) that M982 TbpB relatively obtains or the (ii) TbpB of the bacterial strain of B16 mark type, has the bacterial strain of the TbpB gene of about 1.8kb.
Therefore, pharmaceutical composition of the present invention can comprise in addition that the homology degree that (i) has a sequence that the amino acid from the 1st to the 691st of itself and SEQIDNO:4 shows is at least 85%, preferably the TbpB of at least 90% aminoacid sequence; Or the (ii) fragment of described TbpB.The TbpB that preferably has the M982 bacterial strain of the aminoacid sequence that is shown in SEQIDNO:4.
Pharmaceutical composition of the present invention comprises in addition that also the homology degree that (i) has a sequence that the 1st to the 579th the amino acid of itself and SEQIDNO:8 shows is at least 95%, preferably the TbpB of the aminoacid sequence of 100% (bacterial strain of B16B6 type); Or the (ii) fragment of described TbpB.
As the replaceable form of various possible other TbpB, it is possible using its fragment.Can be as the definite useful fragment of WO95/33049 explanation.
The TbpB that can be used for the object of the invention can be the dissociated form of high molecular (Tbp1) subunit from the meningitis naphthalene Se Shi coccus bacterial strain of the TbpB that derives, or another kind of optionally method and this Tbp1 bonded form, so formed the complex body of the Tbp1-TbpB that is considered for the human transferrin acceptor; In other words, they can be lacked the form of corresponding high molecular (Tbp1) subunit or another kind optionally with its bonded form so that form HTR.No matter the complex body form of the form of dissociating or Tbp1-TbpB, TbpB of the present invention subunit should be a purifying basically; Promptly isolating from its naturally occurring medium.Particularly, especially can be about the kytoplasm that do not have meningitis naphthalene Se Shi coccus and the preparation of peripherin matter.
The TbpB that can be used for the object of the invention can be the dissociated form of high molecular (Tbp1) subunit from the meningitis naphthalene Se Shi coccus bacterial strain of the TbpB that derives, or another kind of optionally method and this Tbp1 bonded form, therefore formed the complex body of being gone back as the Tbp1-TbpB of human transferrin acceptor.No matter the complex form of the form of dissociating or Tbp1-TbpB, TbpB of the present invention subunit should be a purifying basically; Promptly isolating from its naturally occurring medium.Particularly, especially can be about the kytoplasm that do not have meningitis naphthalene Se Shi coccus and the preparation of peripherin matter.
For the purposes of the present invention, use one or more according to the inventive method (particularly referring to WO97/13860) from one or more TbpB of meningococcus purifying or homology or heterologous expression system, obtain by the reorganization approach.
Appropriate expression system is in those skilled in that art's limit of power, because they grasp the gene order of TbpB.Need to make up specific expression cassette, wherein encoding mature TbpB or its segmental dna fragmentation can place under the control of suitable promotor.This dna fragmentation can merge (or not merging) with the DNA piece of coding homology signal peptide or encoding heterologous signal peptide, and this depends on whether require the polypeptide secretion.Preferably, require such secretion use to be derived from the signal sequence of the gene of encoding apolipoprotein.
For example the DNA piece of encoding heterologous signal peptide (signal area) or promotor are to exist quite in a large number and to be that those skilled in that art are known.Their general ability can be selected signal area or specific promotor, and this promotor is applicable to that imagination realizes the host cell of expressing.
For the purposes of the present invention, host cell can be a mammalian cell, bacterium or yeast; 2 of backs are preferred.Again, the selection of specific clone is in those skilled in that art's limit of power.
The present invention also relates to pharmaceutical composition, comprise that coding (i) has the TbpB of human transferrin acceptor (HTR) of meningitis naphthalene Se Shi coccus bacterial strain of the dna sequence dna of coding TbpB, or the (ii) segmental dna molecular amount of described TbpB, wherein the dna sequence dna (a) in (i) contains 2 AvaII restriction sites, 3 HincII restriction sites, do not have VspI and XhoI restriction site or, (b) primer P4 of being 5 '-GAAGACGAGTCGGAAACAAAGGGATG-3 ' by means of primer P3 and the general formula of general formula 5 '-AAGACCAAGGCGGATACGGTTTTGC-3 ' preferably, can produce 765 to 775 Nucleotide, the preferably polynucleotide of 772 Nucleotide (bacterial strain of BZ83 cohort) from this sequence by PCR (polymerase chain reaction).
Preferably, coding is subordinated to the dna molecular of the TbpB that the meningitis naphthalene Se Shi coccus of ET-5 complex body or pedigree III obtains.
According to embodiment preferred, the TbpB that this dna molecule encode obtains from the meningitis naphthalene Se Shi coccus bacterial strain of dna sequence dna with coding TbpB, described dna sequence dna shows by 1184,477 and the AvaII restriction map formed of 3 fragments of 415nt, and by 1155,385,276 and the HincII restriction map formed of 4 fragments of 257nt.Preferably, this dna molecule encode has the TbpB as the described aminoacid sequence of SEQIDNO:2 (bacterial strain BZ83).
Composition based on DNA according to the present invention comprise in addition coding (i) from meningitis naphthalene Se Shi coccus obtain as the part of ET-5 complex body and have the TbpB of the dna sequence dna of coding TbpB, or (ii) first dna molecular of fragment of described TbpB, wherein the dna sequence dna (a) in (i) does not contain AvaII and XhoI restriction site, perhaps, (b) primer P4 of being 5 '-GAAGACGAGTCGGAAACAAAGGGATG-3 ' by means of primer P3 and the general formula of general formula 5 '-AAGACCAAGGCGGATACGGTTTTGC-3 ' preferably, can produce 840 to 850 Nucleotide, the preferably polynucleotide of 844 Nucleotide (bacterial strain of M982 cohort) from this sequence by PCR.
According to embodiment preferred, the TbpB that first other dna molecule encode obtains from the meningitis naphthalene Se Shi coccus bacterial strain of dna sequence dna with coding TbpB, described dna sequence dna contains 1 VspI restriction site and 3 HincII restriction sites.Preferably, this dna molecule encode is from having
The TbpB that the meningitis naphthalene Se Shi coccus bacterial strain of the dna sequence dna of coding TbpB obtains, described dna sequence dna shows by 1311 and the VapI restriction map formed of 2 fragments of 769nt and by 1129,319,281 and the HincII restriction map formed of 4 fragments of 259nt.
Composition based on DNA of the present invention also comprise in addition coding (i) from meningitis naphthalene Se Shi coccus obtain as the part of ET-5 complex body and have the TbpB of the dna sequence dna of coding TbpB, or segmental second other dna molecular of (ii) described second other TbpB, wherein the dna sequence dna (a) in (i) contains 1 AvaII restriction site and 2 VspI restriction sites, 1 XhoI restriction site, perhaps, (b) primer P4 of being 5 '-GAAGACGAGTCGGAAACAAAGGGATG-3 ' by means of primer P3 and the general formula of general formula 5 '-AAGACCAAGGCGGATACGGTTTTGC-3 ' preferably, can produce 800 to 810 Nucleotide, the preferably polynucleotide of 805 Nucleotide (bacterial strains of 8680 cohorts) from this sequence by PCR.
According to embodiment preferred, the TbpB that second other dna molecule encode obtains from the meningitis naphthalene Se Shi coccus bacterial strain of dna sequence dna with coding TbpB, described dna sequence dna shows by 1507 and the AvaII restriction map formed of 2 fragments of 445nt, by 1298,470 and the VspI restriction map formed of 3 fragments of 266nt and by 1551 and the XhoI restriction map formed of 2 fragments of 483nt, with by 1191,527 and the HincII restriction map formed of 3 fragments of 316nt.Preferably, this dna molecule encode has the TbpB (bacterial strain 8680) of the aminoacid sequence that is shown in SEQIDNO:6.
Composition based on DNA of the present invention comprises that in addition the homology degree that coding (i) has a sequence that itself and SEQIDNO:4 show is at least 85%, preferably the TbpB of the aminoacid sequence of at least 90% (M982 type); Or the (ii) segmental dna molecular of described TbpB.Preferably, it is the dna molecular of TbpB that coding has the aminoacid sequence that is shown in SEQIDNO:4 of M982 bacterial strain.
Composition based on DNA of the present invention comprises in addition that also the homology degree that coding (i) has a sequence that itself and SEQIDNO:8 show is at least 95%, preferably the TbpB of the aminoacid sequence of 100% (bacterial strain of B16B6 type); Or the (ii) segmental dna molecular of described TbpB.
Dna molecular preferably can not duplicate and be incorporated into basically the genomic plasmid of animal simultaneously.Above-mentioned encoding sequence places permission under the control of mammalian cell expression promoter.This promotor can be ubiquitous or be specific to the promotor of tissue.In ubiquitous promotor, can mention cytomegalovirus early promoter (being described in United States Patent (USP) 4,168,062) and Rous sarcoma virus promotor and (be described in Norton﹠amp; Coffin, cellular elements biology (1985) 5:281).Desmin promotor (people such as Li, gene (1989) 78:244443; Li﹠amp; Paulin, journal of biological chemistry (1993) 268:10403) be selective actuation, it allows to express in muscle cell, and also expresses in skin cells.In the specific promotor of muscle cell is the promotor of myosin or dystrophin gene for example.The plasmid vector that can be used for the object of the invention is described in as people such as WO94/21797 and hartikka, people's gene treatment (1996) 7:1205.
In the composition based on DNA of the present invention, dna molecular (one or more) can yes or no preparation.The selection of prescription is a height change.This DNA can be simple dilution in the acceptable solution of the physiology that is with or without vehicle.When the latter existed, it can be that isoosmotic or weak height oozes and have low ionic strength.For example these conditions can be to be met by for example 20% sucrose solution.
Another kind of optionally method, dna molecular can be to combine with the reagent that helps to enter cell.This can be a chemical reagent of (ii) modifying cell permeability, for example bupivacaine (referring to for example WO94/16737) or (ii) combine and have the reagent of effect of the carrier of the transportation that helps polynucleotide with polynucleotide.The for example smart ammonia derivative of particularly anionoid polymerization style of the latter such as polylysine or polyamine (referring to WO93/18759).Also can be for example GALA or Gramicidin S (referring to WO93/19768) or the another kind of peptide that optionally derives from virus amalgamation protein matter of fusogenic peptide.
They also can be negatively charged ion or cationic lipid.For a long time known anionic or neutral fat can, for example with the liposome form, as the transportation agent of a large amount of compounds that comprises polynucleotide.The formation of these liposomes and preparation method's detailed description are provided by Liposomes: a kind of hands-on approach PRC new edition, IRL publishes (1990).
Positively charged ion lipid also is known and generally is used as the transportation agent of polynucleotide.Lipofectin for example
TMAlso known its name is called DOTMA, and ((1-(2 for N-, 3-two oleoyl oxygen)-propyl group)-N, N, the N-trimethyl ammonium chloride), DOTAP (1, two (oleoyl oxygen)-3-(Trimethylamine) propane of 2-), DDAB (dimethyl octacosyl brometo de amonio), DOGS (two or two stearylamide glycyl arginine) and cholesterol derivative be DC-courage steroid (3-β-(N-(N ', N '-dimethyl amine ethane)-carboxamide) cholesterol) for example.The description of these lipids is by EP187, and 702, WO90/11092, United States Patent (USP) 5,283,185, WO91/15501, WO95/26356 and United States Patent (USP) 5,527,928 provide.Positively charged ion lipid is preferably with for example DOPE (DOPE) use of neutral lipid, as describing in WO90/11092.
The microparticle of gold or tungsten also can be used as the transportation agent, and as at WO91/359, people such as WO93/17706 and Tang describe among nature (1992) 356:152.Under this specific situation, in the presence of calcium chloride and arginine, polynucleotide is mixed microparticle, for example be described in United States Patent (USP) 4 at the equipment that does not have syringe then, 945,050 and 5,015,580 and WO94/24243 help down, by high-velocity jet to skin or corium with this integral particle administration.
The amount that can be used for the immunization DNA of individual depends on that a plurality of factors for example are used for the intensity of the promotor of antigen expressed, the antigenicity of expressed products, the mammiferous state (for example weight, age and total healthy state) of plan administration, the type of administering mode and preparation.Specified that the intramuscular route of administration needs more substantial DNA than the intradermal administration approach at the equipment that does not have syringe.Usually, the prevention of using for the grownup or the suitable dosage of treatment be about 1 microgram to about 5 milligrams, preferably month 10 micrograms are that about 25 micrograms are to about 500 micrograms to about 1 milligram and most preferred mode.
When the composition based on DNA of the present invention contains several dna moleculars (TbpB of the TbpB of a coding BZ83 bacterial strain and the bacterial strain of another encode another cohort or type), these molecules can exist (for example plasmid/encoding sequence) or another kind of optionally method can constitute one or more units (for example with identical plasmid/two encoding sequence or more) in mode disconnected from each other.
Composition based on DNA of the present invention can contain the compound except the immunizing agent of itself in addition, and the characteristic of these compounds is somewhat dependent upon route of administration.Therefore, as mentioned above, pharmaceutical composition can comprise various preparations.As information, point out that common dna molecular does not need to add auxiliary agent.
Pharmaceutical composition of the present invention is particularly useful for inducing the immunne response, particularly Immunization of the anti-meningitis naphthalene of people Se Shi coccus so that by stoping or the human infection of avoiding meningitis naphthalene Se Shi coccus of treatment protection.
Pharmaceutical composition of the present invention can prepare in the usual way.Especially, can with the pharmacology acceptable diluent, carrier or vehicle for example water or salt brine solution are prepared together.Usually, select thinner or vehicle according to the mode of administration and approach with according to the medicinal practice of standard.Suitable carriers or thinner and produce the essential substance description of pharmaceutical composition in Remington pharmaceutical science (the canonical reference book in this area).Composition based on TbpB also can contain auxiliary agent.
Pharmaceutical composition of the present invention can be by the conventional route of administration administration of using in any vaccine field.Preferably, can use the whole body administration, as the parenteral route administration, itself is selected from vein, intramuscular, transdermal, subcutaneous and administration; But intravenous route preferably in the back.
In order to obtain protection or therapeutic action, the operation of pharmaceutical composition administration of the present invention can be repeated once or several times, between each time administration certain intervals is arranged; This is a week or one month at interval.Those skilled in that art can accurately determine and should the time with the various factors characteristic of immunoreagent for example, individual age or the like and changing.All documents that the application quotes are as the reference of this paper.
Embodiment 1
Contain four bacterial strains and render a service (BZ83,8680, M982 and B16B6)
Meningococcal vaccine
1A. the purifying of natural HTRs
HTR according to each bacterial strain of method purifying of the HTR of embodiment 1 usefulness 8680 bacterial strains that are described in WO97/13860.
1B. the purifying of natural TbpB
The TbpB of each bacterial strain of method purifying that is used for the TbpB of 8680 bacterial strains according to the embodiment 2 that is described in WO97/13860.
1C.TbpB the preparation of recombinant chou
For each TbpB, the construction expression plasmid, wherein sequence and the intestinal bacteria r1pB signal sequence with the TbpB of encoding mature merges (people such as Takase, bacteriology magazine (1983), 169:50692) and place (mouse Salmonellas (people such as Hprwitz, gene (1981) 14:309, people such as Cagnon under the control of araB promotor, protein engineering (1991) 4 (7): 843 and people such as Legrain, protein expression and purifying (1995) 6:570).
These plasmids also contain function replication origin in intestinal bacteria, kantlex are had the gene and the cer site (Summer﹠amp of resistance; Sherratt, cell (1984) 36:1097).
Each plasmid has the function of transformed into escherichia coli BL12 bacterial strain.
In order to produce TbpB, each transformant of selecting is cultivated in the TGM16 substratum that does not have penbritin of 20 liters of fermentor tanks people such as (, protein expression and purifying (1994) 6:518) slos.In exponential phase (optical density(OD) of 600 nanometers is greater than 40), add 0.2% pectinose (induced expression agent).After inducing one hour, collecting cell and be stored in-20 ℃.
Bacterial precipitation is suspended in the Tris damping fluid and carries out high pressure cracking (Rannie).Carry out a series of washings and centrifugal subsequently.Final resolution of precipitate is in the Tris damping fluid that contains both sexes Z3-14 and centrifugal then.Sample is to the Q-agarose column on the supernatant liquor.To contain on the direct elutriant of TbpB sample to the second a Q-agarose column and with TbpB sodium-chlor gradient elution.In order to remove degraded product and intracellular toxin, contain the component of TbpB by gel-filtration purifying on the S-300 chromatography column.Final preparation is by filtering and freezing sterilization.
1D. vaccine composition
Will be as 4 HTR of the description of embodiment 1A preparation, or as 4 TbpB of the description preparation of embodiment 1B, or use together as 4 TbpB that the description of embodiment 1C prepares.
By with BZ83,8680, be that other TbpB of 0.2 mg/ml level obtains vaccine composition thereby each equimolar amount of the TbpB preparation of M982 and B16B6 mixes so that obtain ultimate density.
Sequence table
(1) total data:
(i) applicant:
(A) title: Pasteur Merieux serums﹠amp; Vaccins
(B) street: No. 58, leclerc street
(C) city: Lyons
(E) country: France
(F) postcode: 69007
(G) phone: 04.72.73.79.31
(H) fax: 04.72.73.78.50
(ii) denomination of invention: have (iii) sequence number of meningococcus vaccine that the BZ83 bacterial strain renders a service: 16
(v) computer-reader form:
(A) media types: tape
(B) computer: IBMPC compatible
(C) operating system: PC-DOS/MS-DOS
(D) software: PatentInRelease#1.0, #1.30 version (EPO)
(2) data of SEQIDNO:1:
(i) sequence signature:
(A) length: 2125 base pairs
(B) type: Nucleotide
(C) chain: strand
(D) topology structure: linearity
(ii) molecule type: DNA (genome)
(vi) initial source:
(B) bacterial strain: meningitis naphthalene Se Shi coccus BZ83
(ix) feature:
(A) title/key: CDS
(B) position: 1..2067
(ix) feature:
(A) title/key: sig-peptide
(B) position: 1..60
(ix) feature:
(A) title/key: mat-peptide
(B) position: 61..2067
(xi) sequence description: SEQIDNO:1ATG AAC AAT CCA TTG GTA AAT CAG GCT GCT ATG GTG CTG CCT GTG TTTMet Asn Asn Pro Leu Val Asn Gln Ala Ala Met Val Leu Pro Val Phe-20-15-10-5TTG TTG AGT GCT TGT CTG GGC GGA GGC GGC AGT TTC GAT CTT GAT TCT 96Leu Leu Ser Ala Cys Leu Gly Gly Gly Gly Ser Phe Asp Leu Asp Ser
1???????????????5??????????????????10GTC?GAT?ACC?GAA?GCC?CCG?CGT?CCC?GCG?CCA?AAG?TAT?CAA?GAT?GTT?TCT????????144Val?Asp?Thr?Glu?Ala?Pro?Arg?Pro?Ala?Pro?Lys?Tyr?Gln?Asp?Val?Ser
15??????????????????20??????????????????25TCC?GAA?ACA?CCG?CAA?GCC?CAA?AAA?GAC?CAA?GGC?GGA?TAC?GGT?TTT?GCA????????192Ser?Glu?Thr?Pro?Gln?Ala?Gln?Lys?Asp?Gln?Gly?Gly?Tyr?Gly?Phe?Ala
30??????????????????35?????????????????40ATG?CGC?TTC?AAG?CGG?CGG?AAT?TGG?TAC?CCA?AAA?AAT?GAA?GAA?GAT?CAT????????240Met?Arg?Phe?Lys?Arg?Arg?Asn?Trp?Tyr?Pro?Lys?Asn?Glu?Glu?Asp?His?45??????????????????50??????????????????55??????????????????60AAG?GCA?TTA?TCA?GAA?GCG?GAT?TGG?GAG?AAG?TTA?GGT?GCG?GGT?AAG?CCA????????288Lys?Ala?Leu?Ser?Glu?Ala?Asp?Trp?Glu?Lys?Leu?Gly?Ala?Gly?Lys?Pro
65??????????????????70??????????????????75GAT?GAG?TTT?CCC?CAA?AGG?AAT?GAA?ATA?TTG?AAT?ATG?ACT?GAC?GGA?ATT????????336Asp?Glu?Phe?Pro?Gln?Arg?Asn?Glu?Ile?Leu?Asn?Met?Thr?Asp?Gly?Ile
80??????????????????85??????????????????90CTG?AGT?GAG?TCT?CTT?CAG?CTG?GGT?GAG?GGC?GGC?AAA?AGC?CGC?GTA?GAA????????384Leu?Ser?Glu?Ser?Leu?Gln?Leu?Gly?Glu?Gly?Gly?Lys?Ser?Arg?Val?Glu
95?????????????????100?????????????????105GGA?TAC?ACG?GAT?TTC?CAA?TAT?GTC?CGC?TCG?GGC?TAT?ATC?TAC?CGC?AAC????????432Gly?Tyr?Thr?Asp?Phe?Gln?Tyr?Val?Arg?Ser?Gly?Tyr?Ile?Tyr?Arg?Asn
110?????????????????115?????????????????120GGT?GCC?AAT?AAA?ATC?GAT?TTC?CAA?AAA?AAA?ATC?GCC?CTT?TCC?GGT?CCG????????480Gly?Ala?Asn?Lys?Ile?Asp?Phe?Gln?Lys?Lys?Ile?Ala?Leu?Ser?Gly?Pro125?????????????????130?????????????????135?????????????????140GAC?GGC?TAC?CTT?TTC?TAC?AAA?GGC?AGC?AAT?CCT?TCC?CAA?GCT?CTG?CCG????????528Asp?Gly?Tyr?Leu?Phe?Tyr?Lys?Gly?Ser?Asn?Pro?Ser?Gln?Ala?Leu?Pro
145?????????????????150?????????????????155ATG?GGT?AAG?GTA?GGT?TAT?AAA?GGT?ACT?TGG?GAT?TAT?GTA?ACC?GAT?GCC????????576Met?Gly?Lys?Val?Gly?Tyr?Lys?Gly?Thr?Trp?Asp?Tyr?Val?Thr?Asp?Ala
160?????????????????165?????????????????170AAG?ATG?GGA?CAA?AAA?TTT?TCC?CAG?TTG?GCT?GGT?TTT?CCA?GCG?GGG?GAT????????624Lys?Met?Gly?Gln?Lys?Phe?Ser?Gln?Leu?Ala?Gly?Phe?Pro?Ala?Gly?Asp
175?????????????????180?????????????????185AGG?TAT?GGG?GCT?TTG?TCT?GCC?GAG?GAA?GCG?GAT?GTG?TTG?CGC?AAC?AAA????????672Arg?Tyr?Gly?Ala?Leu?Ser?Ala?Glu?Glu?Ala?Asp?Val?Leu?Arg?Asn?Lys
190?????????????????195?????????????????200AGC?GAG?GCA?CAG?CAA?GGT?CAG?ACC?GAT?TTC?GGG?CTG?ACC?AGC?GAG?TTT????????720Ser?Glu?Ala?Gln?Gln?Gly?Gln?Thr?Asp?Phe?Gly?Leu?Thr?Ser?Glu?Phe205?????????????????210?????????????????215?????????????????220GAG?GTG?GAT?TTC?GCC?GCC?AAG?ACC?ATG?ACC?GGC?GCG?CTC?TAC?CGC?AAT????????768Glu?Val?Asp?Phe?Ala?Ala?Lys?Thr?Met?Thr?Gly?Ala?Leu?Tyr?Arg?Asn
225?????????????????230?????????????????235AAC?CGG?ATT?ACT?AAT?AAC?GAA?ACC?GAA?AAT?AAA?GCC?AAA?CAA?ATT?AAA???????816Asn?Arg?Ile?Thr?Asn?Asn?Glu?Thr?Glu?Asn?Lys?Ala?Lys?Gln?Ile?Lys
240?????????????????245?????????????????250CGT?TAC?GAC?ATT?CAG?GCT?GAC?CTG?CAC?GGT?AAC?CGC?TTC?AGC?GGC?AAG???????864Arg?Tyr?Asp?Ile?Gln?Ala?Asp?Leu?His?Gly?Asn?Arg?Phe?Ser?Gly?Lys
255?????????????????260?????????????????265GCA?ACG?GCA?ACC?GAC?AAA?CCC?AAA?AAC?GAC?GAA?ACC?AAG?GAA?CAT?CCC???????912Ala?Thr?Ala?Thr?Asp?Lys?Pro?Lys?Asn?Asp?Glu?Thr?Lys?Glu?His?Pro
270?????????????????275?????????????????280TTT?GTT?TCC?GAC?TCG?TCT?TCT?TTG?AGC?GGC?GGC?TTT?TTC?GGT?CCG?AAG???????960Phe?Val?Ser?Asp?Ser?Ser?Ser?Leu?Ser?Gly?Gly?Phe?Phe?Gly?Pro?Lys285?????????????????290?????????????????295?????????????????300GGT?GAG?GAA?TTG?GGT?TTC?CGC?TTT?TTG?AGC?GAC?GAT?CAA?AAA?GTT?GCC???????1008Gly?Glu?Glu?Leu?Gly?Phe?Arg?Phe?Leu?Ser?Asp?Asp?Gln?Lys?Val?Ala
305?????????????????310?????????????????315GTT?GTC?GGC?AGC?GCG?AAA?ACC?AAA?GAC?AAA?CTG?GAA?AAT?GGC?GCG?GCG???????1056Val?Val?Gly?Ser?Ala?Lys?Thr?Lys?Asp?Lys?Leu?Glu?Asn?Gly?Ala?Ala
320?????????????????325?????????????????330GCT?TCA?GGC?AGC?ACA?GGT?GCG?GCA?GCA?TCG?GGC?GGT?GCG?GCA?GAT?ATG???????1104Ala?Ser?Gly?Ser?Thr?Gly?Ala?Ala?Ala?Ser?Gly?Gly?Ala?Ala?Asp?Met
335?????????????????340?????????????????345CCG?TCT?GAA?AAC?GGT?AAG?CTG?ACC?ACG?GTT?TTG?GAT?GCG?GTT?GAG?CTG???????1152Pro?Ser?Glu?Asn?Gly?Lys?Leu?Thr?Thr?Val?Leu?Asp?Ala?Val?Glu?Leu
350?????????????????355?????????????????360AAA?TCT?GGC?GGT?AAG?GAA?GTC?AAA?AAT?CTC?GAC?AAC?TTC?AGC?AAT?GCC???????1200Lys?Ser?Gly?Gly?Lys?Glu?Val?Lys?Asn?Leu?Asp?Asn?Phe?Ser?Asn?Ala365?????????????????370?????????????????375?????????????????380GCC?CAA?CTG?GTT?GTC?GAC?GGC?ATT?ATG?ATT?CCG?CTC?CTG?CCC?AAG?AAT???????1248Ala?Gln?Leu?Val?Val?Asp?Gly?Ils?Met?Ile?Pro?Leu?Leu?Pro?Lys?Asn
385?????????????????390?????????????????395TCC?GAA?AGC?GAG?AGC?AAT?CAG?GCA?GAT?AAA?GGT?AAA?AAC?GGC?GGA?ACA???????1296Ser?Glu?Ser?Glu?Ser?Asn?Gln?Ala?Asp?Lys?Gly?Lys?Asn?Gly?Gly?Thr
400?????????????????405?????????????????410GCC?TTT?ACC?CGC?AAA?TTT?GAA?CAC?ACG?CCG?GAA?AGT?GAT?AAA?AAA?GAC???????1344Ala?Phe?Thr?Arg?Lys?Phe?Glu?His?Thr?Pro?Glu?ser?Asp?Lys?Lys?Asp
415?????????????????420?????????????????425ACC?CAA?GCA?GGT?ACG?GCG?GAG?AAT?GGC?AAT?CCA?GCC?GCT?TCA?AAT?ACG???????1392Thr?Gln?Ala?Gly?Thr?Ala?Glu?Asn?Gly?Asn?Pro?Ala?Ala?Ser?Asn?Thr
430?????????????????435?????????????????440GCA?GGT?GAT?ACC?AAT?GGC?AAA?ACA?AAA?ACC?TAT?GAA?GTC?GAA?GTC?TGC???????1440Ala?Gly?Asp?Thr?Asn?Gly?Lys?Thr?Lys?Thr?Tyr?Glu?Val?Glu?Val?Cys445?????????????????450?????????????????455?????????????????460TGT?TCC?AAC?CTC?AAT?TAT?CTG?AAA?TAC?GGA?ATG?TTG?ACG?CGT?AAA?AAC???????1488Cys?Ser?Asn?Leu?Asn?Tyr?Leu?Lys?Tyr?Gly?Met?Leu?Thr?Arg?Lys?Asn
465?????????????????470?????????????????475AGC?AAG?TCC?GCG?ATG?CAG?GCA?GGC?GAA?AAC?GGT?AGT?CTA?GCT?GAC?GCT???????1536Ser?Lys?Ser?Ala?Met?Gln?Ala?Gly?Glu?Asn?Gly?Ser?Leu?Ala?Asp?Ala
480?????????????????485?????????????????490AAA?ACG?GAA?CAA?GTT?GAA?CAA?AGT?ATG?TTC?CTC?CAA?GGC?GAG?CGC?ACC???????1584Lys?Thr?Glu?Gln?Val?Glu?Gln?Ser?Met?Phe?Leu?Gln?Gly?Glu?Arg?Thr
495?????????????????500?????????????????505GAT?GAA?AAA?GAG?ATT?CCA?AAA?GAG?CAA?CAA?GAC?ATC?GTT?TAT?CGG?GGG???????1632Asp?Glu?Lys?Glu?Ile?Pro?Lys?Glu?Gln?Gln?Asp?Ile?Val?Tyr?Arg?Gly
510?????????????????515?????????????????520TCT?TGG?TAC?GGG?CAT?ATT?GCC?AAC?GAC?ACA?AGC?TGG?AGC?GGC?AAT?GCT???????1680Ser?Trp?Tyr?Gly?His?Ile?Ala?Asn?Asp?Thr?Ser?Trp?Ser?Gly?Asn?Ala525?????????????????530?????????????????535?????????????????540TCA?GAT?AGA?GAG?GGC?GGC?AAC?AGG?GCG?GAC?TTT?ACC?GTG?AAT?TTT?GGT???????1728Ser?Asp?Arg?Glu?Gly?Gly?Asn?Arg?Ala?Asp?Phe?Thr?Val?Asn?Phe?Gly
545?????????????????550?????????????????555ACG?AAA?AAA?ATT?AAC?GGA?ACG?TTA?ACC?GCT?GAA?AAC?AGG?CAG?GAG?GCA???????1776Thr?Lys?Lys?Ile?Asn?Gly?Thr?Leu?Thr?Ala?Glu?Asn?Arg?Gln?Glu?Ala
560?????????????????565?????????????????570ACC?TTT?ACC?ATT?GTG?GGC?GAT?ATT?AAG?GAC?AAC?GGC?TTT?GAA?GGT?ACG???????1824Thr?Phe?Thr?Ile?Val?Gly?Asp?Ile?Lys?Asp?Asn?Gly?Phe?Glu?Gly?Thr
575?????????????????580?????????????????585GCG?AAA?ACT?GCT?GAC?TCA?GGT?TTT?GAT?CTC?GAT?CAA?AGC?AAT?ACC?ACC???????1872Ala?Lys?Thr?Ala?Asp?Ser?Gly?Phe?Asp?Leu?Asp?Gln?Ser?Asn?Thr?Thr
590?????????????????595?????????????????600CGC?ACG?CCT?AAG?GCA?TAT?ATC?ACA?GAT?GCC?AAG?GTG?AAG?GGC?GGT?TTT???????1920Arg?Thr?Pro?Lys?Ala?Tyr?Ile?Thr?Asp?Ala?Lys?Val?Lys?Gly?Gly?Phe605?????????????????610?????????????????615?????????????????620TAC?GGG?CCT?AAA?GCC?GAA?GAG?TTG?GGC?GGA?TGG?TTT?GCC?TAT?CCG?GGC???????1968Tyr?Gly?Pro?Lys?Ala?Glu?Glu?Leu?Gly?Gly?Trp?Phe?Ala?Tyr?Pro?Gly
625?????????????????630?????????????????635GAT?AAA?CAA?ACG?GAA?AAG?GCA?ACG?GTT?ACA?TCC?GGC?GAT?GGA?AAT?TCA???????2016Asp?Lys?Gln?Thr?Glu?Lys?Ala?Thr?Val?Thr?Ser?Gly?Asp?Gly?Asn?Ser
640?????????????????645?????????????????650GCA?AGC?AGT?GCA?ACT?GTC?GTA?TTC?GGT?GCG?AAA?CGC?CAA?AAG?CCT?GTG???????2064Ala?Ser?Ser?Ala?Thr?Val?Val?Phe?Gly?Ala?Lys?Arg?Gln?Lys?Pro?Val
The data of 655 660 665CAA TAAAGTTTCG ATCTTGATTC TGTCGATACC GAAGCCCCGC GTCCCGCGCC AAATAAAA 2125Gln (2) SEQIDNO:2: (i) sequence signature: (A) length: 689 amino acid (B) type: amino acid (D) topology: linear (ii) molecule type: protein (xi) sequence description: SEQIDNO:2Met Asn Asn Pro Leu Val Asn Gln Ala Ala Met Val Leu Pro Val Phe-20-15-10-5Leu Leu Ser Ala Cys Leu Gly Gly Gly Gly Ser Phe Asp Leu Asp Ser
1???????????????5??????????????????10Val?Asp?Thr?Glu?Ala?Pro?Arg?Pro?Ala?Pro?Lys?Tyr?Gln?Asp?Val?Ser
15??????????????????20??????????????????25Ser?Glu?Thr?Pro?Gln?Ala?Gln?Lys?Asp?Gln?Gly?Gly?Tyr?Gly?Phe?Ala
30??????????????????35??????????????????40Met?Arg?Phe?Lys?Arg?Arg?Asn?Trp?Tyr?Pro?Lys?Asn?Glu?Glu?Asp?His?45??????????????????50??????????????????55??????????????????60Lys?Ala?Leu?Ser?Glu?Ala?Asp?Trp?Glu?Lys?Leu?Gly?Ala?Gly?Lys?Pro
65??????????????????70??????????????????75Asp?Glu?Phe?Pro?Gln?Arg?Asn?Glu?Ile?Leu?Asn?Met?Thr?Asp?Gly?Ile
80??????????????????85??????????????????90Leu?Ser?Glu?Ser?Leu?Gln?Leu?Gly?Glu?Gly?Gly?Lys?Ser?Arg?Val?Glu
95?????????????????100?????????????????105Gly?Tyr?Thr?Asp?Phe?Gln?Tyr?Val?Arg?Ser?Gly?Tyr?Ile?Tyr?Arg?Asn
110?????????????????115?????????????????120Gly?Ala?Asn?Lys?Ile?Asp?Phe?Gln?Lys?Lys?Ile?Ala?Leu?Ser?Gly?Pro125?????????????????130?????????????????135?????????????????140Asp?Gly?Tyr?Leu?Phe?Tyr?Lys?Gly?Ser?Asn?Pro?Ser?Gln?Ala?Leu?Pro
145?????????????????150?????????????????155Met?Gly?Lys?Val?Gly?Tyr?Lys?Gly?Thr?Trp?Asp?Tyr?Val?Thr?Asp?Ala
160?????????????????165?????????????????170Lys?Met?Gly?Gln?Lys?Phe?Ser?Gln?Leu?Ala?Gly?Phe?Pro?Ala?Gly?Asp
175?????????????????180?????????????????185Arg?Tyr?Gly?Ala?Leu?Ser?Ala?Glu?Glu?Ala?Asp?Val?Leu?Arg?Asn?Lys
190?????????????????195?????????????????200Ser?Glu?Ala?Gln?Gln?Gly?Gln?Thr?Asp?Phe?Gly?Leu?Thr?Ser?Glu?Phe205?????????????????210?????????????????215?????????????????220Glu?Val?Asp?Phe?Ala?Ala?Lys?Thr?Met?Thr?Gly?Ala?Leu?Tyr?Arg?Asn
225?????????????????230?????????????????235Asn?Arg?Ile?Thr?Asn?Asn?Glu?Thr?Glu?Asn?Lys?Ala?Lys?Gln?Ile?Lys
240?????????????????245?????????????????250Arg?Tyr?Asp?Ile?Gln?Ala?Asp?Leu?His?Gly?Asn?Arg?Phe?Ser?Gly?Lys
255?????????????????260?????????????????265Ala?Thr?Ala?Thr?Asp?Lys?Pro?Lys?Asn?Asp?Glu?Thr?Lys?Glu?His?Pro
270?????????????????275?????????????????280Phe?Val?Ser?Asp?Ser?Ser?Ser?Leu?Ser?Gly?Gly?Phe?Phe?Gly?Pro?Lys285?????????????????290?????????????????295?????????????????300Gly?Glu?Glu?Leu?Gly?Phe?Arg?Phe?Leu?Ser?Asp?Asp?Gln?Lys?Val?Ala
305?????????????????310?????????????????315Val?Val?Gly?Ser?Ala?Lys?Thr?Lys?Asp?Lys?Leu?Glu?Asn?Gly?Ala?Ala
320?????????????????325?????????????????330Ala?Ser?Gly?Ser?Thr?Gly?Ala?Ala?Ala?Ser?Gly?Gly?Ala?Ala?Asp?Met
335?????????????????340?????????????????345Pro?Ser?Glu?Asn?Gly?Lys?Leu?Thr?Thr?Val?Leu?Asp?Ala?Val?Glu?Leu
350?????????????????355?????????????????360Lys?Ser?Gly?Gly?Lys?Glu?Val?Lys?Asn?Leu?Asp?Asn?Phe?Ser?Asn?Ala365?????????????????370?????????????????375?????????????????380Ala?Gln?Leu?Val?Val?Asp?Gly?Ile?Met?Ile?Pro?Leu?Leu?Pro?Lys?Asn
385?????????????????390?????????????????395Ser?Glu?Ser?Glu?Ser?Asn?Gln?Ala?Asp?Lys?Gly?Lys?Asn?Gly?Gly?Thr
400?????????????????405?????????????????410Ala?Phe?Thr?Arg?Lys?Phe?Glu?His?Thr?Pro?Glu?Ser?Asp?Lys?Lys?Asp
415?????????????????420?????????????????425Thr?Gln?Ala?Gly?Thr?Ala?Glu?Asn?Gly?Asn?Pro?Ala?Ala?Ser?Asn?Thr
430?????????????????435?????????????????440Ala?Gly?Asp?Thr?Asn?Gly?Lys?Thr?Lys?Thr?Tyr?Glu?Val?Glu?Val?Cys445?????????????????450?????????????????455?????????????????460Cys?Ser?Asn?Leu?Asn?Tyr?Leu?Lys?Tyr?Gly?Met?Leu?Thr?Arg?Lys?Asn
465?????????????????470?????????????????475Ser?Lys?Ser?Ala?Met?Gln?Ala?Gly?Glu?Asn?Gly?Ser?Leu?Ala?Asp?Ala
480?????????????????485?????????????????490Lys?Thr?Glu?Gln?Val?Glu?Gln?Ser?Met?Phe?Leu?Gln?Gly?Glu?Arg?Thr
495?????????????????500?????????????????505Asp?Glu?Lys?Glu?Ile?Pro?Lys?Glu?Gln?Gln?Asp?Ile?Val?Tyr?Arg?Gly
510?????????????????515?????????????????520Ser?Trp?Tyr?Gly?His?Ile?Ala?Asn?Asp?Thr?Ser?Trp?Ser?Gly?Asn?Ala525?????????????????530?????????????????535?????????????????540Ser?Asp?Arg?Glu?Gly?Gly?Asn?Arg?Ala?Asp?Phe?Thr?Val?Asn?Phe?Gly
545?????????????????550?????????????????555Thr?Lys?Lys?Ile?Asn?Gly?Thr?Leu?Thr?Ala?Glu?Asn?Arg?Gln?Glu?Ala
560?????????????????565?????????????????570Thr?Phe?Thr?Ile?Val?Gly?Asp?Ile?Lys?Asp?Asn?Gly?Phe?Glu?Gly?Thr
575?????????????????580?????????????????585Ala?Lys?Thr?Ala?Asp?Ser?Gly?Phe?Asp?Leu?Asp?Gln?Ser?Asn?Thr?Thr
590?????????????????595?????????????????600Arg?Thr?Pro?Lys?Ala?Tyr?Ile?Thr?Asp?Ala?Lys?Val?Lys?Gly?Gly?Phe605?????????????????610?????????????????615?????????????????620Tyr?Gly?Pro?Lys?Ala?Glu?Glu?Leu?Gly?Gly?Trp?Phe?Ala?Tyr?Pro?Gly
625?????????????????630?????????????????635Asp?Lys?Gln?Thr?Glu?Lys?Ala?Thr?Val?Thr?Ser?Gly?Asp?Gly?Asn?Ser
640?????????????????645?????????????????650Ala?Ser?Ser?Ala?Thr?Val?Val?Phe?Gly?Ala?Lys?Arg?Gln?Lys?Pro?Val
655?????????????????660?????????????????665Gln
(2) data of SEQIDNO:3:
(i) sequence signature:
(A) length: 2040 base pairs
(B) type: Nucleotide
(C) chain: two strands
(D) topology structure: linearity
(ii) molecule type: DNA (genome)
(vi) initial source:
(B) bacterial strain: meningitis naphthalene Se Shi coccus 32/94
(ix) feature:
(A) title/key: CDS
(B) position: 1..2040
(ix) feature:
(A) title/key: sig-peptide
(B) position: 1..30
(ix) feature:
(A) title/key: mat-peptide
(B) position: 31..2040
(xi) sequence description: SEQIDNO:3ATG GTG CTG CCT GTG TTT TTG TTG AGT GCT TGT CTG GGC GGA GGC GGC 48Met Val Leu Pro Val Phe Leu Leu Ser Ala Cys Leu Gly Gly Gly Gly-10-5 1 5AGT TTC GAT CTT GAT TCT GTC GAT ACC GAA GCC CCG CGT CCC GCG CCA 96Ser Phe Asp Leu Asp Ser Val Asp Thr Glu Ala Pro Arg Pro Ala Pro
10??????????????????15??????????????????20AAG?TAT?CAA?GAT?GTC?TCT?TCC?GAA?ACA?CCG?CAA?GCC?CAA?AAA?GAC?CAA????????144Lys?Tyr?Gln?Asp?Val?Ser?Ser?Glu?Thr?Pro?Gln?Ala?Gln?Lys?Asp?Gln
25??????????????????30??????????????????35GGC?GGA?TAC?GGT?TTT?GCA?ATG?CGC?TTC?AAG?CGG?CGG?AAT?TGG?TAC?CCA????????192Gly?Gly?Tyr?Gly?Phe?Ala?Met?Arg?Phe?Lys?Arg?Arg?Asn?Trp?Tyr?Pro
40??????????????????45??????????????????50AAA?AAT?GAA?GAA?GAT?CAT?AAG?GCA?TTA?TCA?GAA?GCG?GAT?TGG?GAG?AAG????????240Lys?Asn?Glu?Glu?Asp?His?Lys?Ala?Leu?Ser?Glu?Ala?Asp?Trp?Glu?Lys?55??????????????????60??????????????????65??????????????????70TTA?GGT?GCG?GGT?AAG?CCA?GAT?GAG?TTT?CCC?CAA?AGG?AAT?GAA?ATA?TTG????????288Leu?Gly?Ala?Gly?Lys?Pro?Asp?Glu?Phe?Pro?Gln?Arg?Asn?Glu?Ile?Leu
75??????????????????80??????????????????85AAT?ATG?ACT?GAC?GGA?ATT?CTG?AGT?GAG?TCT?CTT?CAG?CTG?GGT?GAG?GGC????????336Asn?Met?Thr?Asp?Gly?Ile?Leu?Ser?Glu?Ser?Leu?Gln?Leu?Gly?Glu?Gly
90??????????????????95?????????????????100GGC?AAA?AGC?CGC?GTA?GAA?GGA?TAC?ACG?GAT?TTC?CAG?TAT?GTC?CGC?TCG????????384Gly?Lys?Ser?Arg?Val?Glu?Gly?Tyr?Thr?Asp?Phe?Gln?Tyr?Val?Arg?Ser
105?????????????????110?????????????????115GGC?TAT?ATC?TAC?CGC?AAC?GGT?GCC?AAT?AAA?ATC?GAT?TTC?CAA?AAA?AAA????????432Gly?Tyr?Ile?Tyr?Arg?Asn?Gly?Ala?Asn?Lys?Ile?Asp?Phe?Gln?Lys?Lys
120?????????????????125?????????????????130ATC?GCC?CTT?TCC?GGT?CCG?GAC?GGC?TAC?CTT?TTC?TAC?AAA?GGC?AGC?AAT????????480Ile?Ala?Leu?Ser?Gly?Pro?Asp?Gly?Tyr?Leu?Phe?Tyr?Lys?Gly?Ser?Asn135?????????????????140?????????????????145?????????????????150CCT?TCC?CAA?GCT?CTG?CCG?ATG?GGT?AAG?GTA?GGT?TAT?AAA?GGT?ACT?TGG????????528Pro?Ser?Gln?Ala?Leu?Pro?Met?Gly?Lys?Val?Gly?Tyr?Lys?Gly?Thr?Trp
155?????????????????160?????????????????165GAT?TAT?GTA?ACC?GAT?GCC?AAG?ATG?GGA?CAA?AAA?TTT?TCC?CAG?TTG?GCT????????576Asp?Tyr?Val?Thr?Asp?Ala?Lys?Met?Gly?Gln?Lys?Phe?Ser?Gln?Leu?Ala
170?????????????????175?????????????????180GGT?TTT?CCA?GCG?GGG?GAT?AGG?TAT?GGG?GCT?TTG?TCT?GCC?GAG?GAA?GCG????????624Gly?Phe?Pro?Ala?Gly?Asp?Arg?Tyr?Gly?Ala?Leu?Ser?Ala?Glu?Glu?Ala
185?????????????????190?????????????????195GAT?GTG?TTG?CGC?AAC?AAA?AGC?GAG?GCA?CAG?CAA?GGT?CAG?ACC?GAT?TTC????????672Asp?Val?Leu?Arg?Asn?Lys?Ser?Glu?Ala?Gln?Gln?Gly?Gln?Thr?Asp?Phe
200?????????????????205?????????????????210GGG?CTG?ACC?AGC?GAG?TTT?GAG?GTG?GAT?TTC?GCC?GCC?AAG?ACC?ATG?ACC????????720Gly?Leu?Thr?Ser?Glu?Phe?Glu?Val?Asp?Phe?Ala?Ala?Lys?Thr?Met?Thr215?????????????????220?????????????????225?????????????????230GGC?GCG?CTC?TAC?CGC?AAT?AAC?CGG?ATT?ACT?AAT?AAC?GAA?ACC?GAA?TAT????????768Gly?Ala?Leu?Tyr?Arg?Asn?Asn?Arg?Ile?Thr?Asn?Asn?Glu?Thr?Glu?Tyr
235?????????????????240?????????????????245AAA?GCC?AAA?CAA?ATT?AAA?CGT?TAC?GAC?ATT?CAG?GCT?GAC?CTG?CAC?GGT?????????816Lys?Ala?Lys?Gln?Ile?Lys?Arg?Tyr?Asp?Ile?Gln?Ala?Asp?Leu?His?Gly
250?????????????????255?????????????????260AAC?CGC?TTC?AGC?GGC?AAG?GCA?ACG?GCA?ACC?GAC?AAA?CCC?AAA?AAC?GAC?????????864Asn?Arg?Phe?Ser?Gly?Lys?Ala?Thr?Ala?Thr?Asp?Lys?Pro?Lys?Asn?Asp
265?????????????????270?????????????????275GAA?ACC?AAG?GAA?CAT?CCC?TTT?GTT?TCC?GAC?TCG?TCT?TCT?TTG?AGC?GGC?????????912Glu?Thr?Lys?Glu?His?Pro?Phe?Val?Ser?Asp?Ser?Ser?Ser?Leu?Ser?Gly
280?????????????????285?????????????????290GGC?TTT?TTC?GGT?CCG?AAG?GGT?GAG?GAA?TTG?GGT?TTC?CGC?TTT?TTG?AGC?????????960Gly?Phe?Phe?Gly?Pro?Lys?Gly?Glu?Glu?Leu?Gly?Phe?Arg?Phe?Leu?Ser295?????????????????300?????????????????305?????????????????310GAC?GAT?CAA?AAA?GTT?GCC?GTT?GTC?GGC?AGC?GCG?AAA?ACC?AAA?GAC?AAA????????1008Asp?Asp?Gln?Lys?Val?Ala?Val?Val?Gly?Ser?Ala?Lys?Thr?Lys?Asp?Lys
315?????????????????320?????????????????325CTG?GAA?AAT?GGC?GCG?GCG?GCT?TCA?GGC?AGC?ACA?GGT?GCG?GCA?GCA?TCG????????1056Leu?Glu?Asn?Gly?Ala?Ala?Ala?Ser?Gly?Ser?Thr?Gly?Ala?Ala?Ala?Ser
330?????????????????335?????????????????340GGC?GGT?GCG?GCA?GAT?ATG?CCG?TCT?GAA?AAC?GGT?AAG?CTG?ACC?ACG?GTT????????1104Gly?Gly?Ala?Ala?Asp?Mer?Pro?Ser?Glu?Asn?Gly?Lys?Leu?Thr?Thr?Val
345?????????????????350?????????????????355TTG?GAT?GCG?ATT?GAG?CTG?AAA?TCT?GGC?GGT?AAG?GAA?GTC?AAA?AAT?CTC????????1152Leu?Asp?Ala?Ile?Glu?Leu?Lys?Ser?Gly?Gly?Lys?Glu?Val?Lys?Asn?Leu
360?????????????????365?????????????????370GAC?AAC?TTC?AGC?AAT?GCC?GCC?CAA?CTG?GTT?GTC?GAC?GGC?ATT?ATG?ATT????????1200Asp?Asn?Phe?Ser?Asn?Ala?Ala?Gln?Leu?Val?Val?Asp?Gly?Ile?Met?Ile375?????????????????380?????????????????385?????????????????390CCG?CTC?CTG?CCC?AAG?AAT?TCC?GAA?AGC?GAG?AGC?AAT?CAG?GCA?GAT?AAA????????1248Pro?Leu?Leu?Pro?Lys?Asn?Ser?Glu?Ser?Glu?Ser?Asn?Gln?Ala?Asp?Lys
395?????????????????400?????????????????405GGT?AAA?AAC?GGC?GGA?ACA?GCC?TTT?ACC?CGC?AAA?TTT?GAA?CAC?ACG?CCG????????1296Gly?Lys?Asn?Gly?Gly?Thr?Ala?Phe?Thr?Arg?Lys?Phe?Glu?His?Thr?Pro
410?????????????????415?????????????????420GAA?AGT?GAT?AAA?AAA?GAC?ACC?CAA?GCA?GGT?ACG?GCG?GAG?AAT?GGC?AAT????????1344Glu?Ser?Asp?Lys?Lys?Asp?Thr?Gln?Ala?Gly?Thr?Ala?Glu?Asn?Gly?Asn
425?????????????????430?????????????????435CCA?GCC?GCT?TCA?AAT?ACG?GCA?GGT?GAT?ACC?AAT?GGC?AAA?ACA?AAA?ACC????????1392Pro?Ala?Ala?Ser?Asn?Thr?Ala?Gly?Asp?Thr?Asn?Gly?Lys?Thr?Lys?Thr
440?????????????????445?????????????????450TAT?GAA?GTC?GAA?GTC?TGC?TGT?TCC?AAC?CTC?AAT?TAT?CTG?AAA?TAC?GGA????????1440Tyr?Glu?Val?Glu?Val?Cys?Cys?Ser?Asn?Leu?Asn?Tyr?Leu?Lys?Tyr?Gly455?????????????????460?????????????????465?????????????????470ATG?TTG?ACG?CGT?GAA?AAC?AGC?AAG?TCC?GCG?ATG?CAG?GCA?GGC?GAA?AAC????????1488Met?Leu?Thr?Arg?Glu?Asn?Ser?Lys?Ser?Ala?Met?Gln?Ala?Gly?Glu?Asn
475?????????????????480?????????????????485GGT?AGT?CAA?GCT?GAC?GCT?AAA?ACG?GAA?CAA?GTT?GAA?CAA?AGT?ATG?TTC???????1536Gly?Ser?Gln?Ala?Asp?Ala?Lys?Thr?Glu?Gln?Val?Glu?Gln?Ser?Met?Phe
490?????????????????495?????????????????500CTC?CAA?GGC?GAG?CGC?ACC?GAT?GAA?AAA?GAG?ATT?CCA?AAA?GAG?CAA?CAA???????1584Leu?Gln?Gly?Glu?Arg?Thr?Asp?Glu?Lys?Glu?Ile?Pro?Lys?Glu?Gln?Gln
505?????????????????510?????????????????515GAC?ATC?GTT?TAT?CGG?GGG?TCT?TGG?TAC?GGG?CAT?ATT?GCC?AAC?GAC?ACA???????1632Asp?Ile?Val?Tyr?Arg?Gly?Ser?Trp?Tyr?Gly?His?Ile?Ala?Asn?Asp?Thr
520?????????????????525?????????????????530AGC?TGG?AGC?GGC?AAT?GCT?TCA?GAT?AGA?GAG?GGC?GGC?AAC?AGG?GCG?GAC???????1680Ser?Trp?Ser?Gly?Asn?Ala?Ser?Asp?Arg?Glu?Gly?Gly?Asn?Arg?Ala?Asp535?????????????????540?????????????????545?????????????????550TTT?ACC?GTG?AAT?TTT?GGT?ACG?AAA?AAA?ATT?AAC?GGA?ACG?TTA?ACC?GCT???????1728Phe?Thr?Val?Asn?Phe?Gly?Thr?Lys?Lys?Ile?Asn?Gly?Thr?Leu?Thr?Ala
555?????????????????560?????????????????565GAA?AAC?AGG?CAG?GAG?GCA?ACC?TTT?ACC?ATT?GTG?GGC?GAT?ATT?AAG?GAC???????1776Glu?Asn?Arg?Gln?Glu?Ala?Thr?Phe?Thr?Ile?Val?Gly?Asp?Ile?Lys?Asp
570?????????????????575?????????????????580AAC?GGC?TTT?GAA?GGT?ACG?GCG?AAA?ACT?GCT?GAC?TCA?GGT?TTT?GAT?CAC???????1824Asn?Gly?Phe?Glu?Gly?Thr?Ala?Lys?Thr?Ala?Asp?Ser?Gly?Phe?Asp?His
585?????????????????590?????????????????595GAT?CAA?AGC?AAT?ACC?ACC?CGC?ACG?CCT?AAG?GCA?TAT?ATC?ACA?GAT?GCC???????1872Asp?Gln?Ser?Asn?Thr?Thr?Arg?Thr?Pro?Lys?Ala?Tyr?Ile?Thr?Asp?Ala
600?????????????????605?????????????????610AAG?GTG?AAG?GGC?GGT?TTT?TAC?GGG?CCT?AAA?GCC?GAA?GAG?TTG?GGC?GGG???????1920Lys?Val?Lys?Gly?Gly?Phe?Tyr?Gly?Pro?Lys?Ala?Glu?Glu?Leu?Gly?Gly615?????????????????620?????????????????625?????????????????630TGG?TTT?GCC?TAT?CCG?GGC?GAT?AAA?CAA?ACG?GAA?AAG?GCA?ACG?GTT?ACA???????1968Trp?Phe?Ala?Tyr?Pro?Gly?Asp?Lys?Gln?Thr?Glu?Lys?Ala?Thr?Val?Thr
635?????????????????640?????????????????645TCC?GGC?GAT?GGA?AAT?TCA?GCA?AGC?AGT?GCA?ACT?GTC?GTA?TTC?GGT?GCG???????2016Ser?Gly?Asp?Gly?Asn?Ser?Ala?Ser?Ser?Ala?Thr?Val?Val?Phe?Gly?Ala
650?????????????????655?????????????????660AAA?CGC?CAA?AAG?CCT?GTG?CAA?TAA???????????????????????????????????????2040Lys?Arg?Gln?Lys?Pro?Val?Gln??*
665 670, (2) data of SEQIDNO:4:, (i) sequence signature:, (A) length: 680 amino acid, (B) type: amino acid, (D) topology structure: linearity, (ii) molecule type: protein, (xi) sequence description: SEQIDNO:4Met Val Leu Pro Val Phe Leu Leu Ser Ala Cys Leu Gly Gly Gly Gly-10-5 1 5Ser Phe Asp Leu Asp Ser Val Asp Thr Glu Ala Pro Arg Pro Ala Pro
10??????????????????15??????????????????20Lys?Tyr?Gln?Asp?Val?Ser?Ser?Glu?Thr?Pro?Gln?Ala?Gln?Lys?Asp?Gln
25??????????????????30??????????????????35Gly?Gly?Tyr?Gly?Phe?Ala?Met?Arg?Phe?Lys?Arg?Arg?Asn?Trp?Tyr?Pro
40??????????????????45??????????????????50Lys?Asn?Glu?Glu?Asp?His?Lys?Ala?Leu?Ser?Glu?Ala?Asp?Trp?Glu?Lys?55??????????????????60??????????????????65??????????????????70Leu?Gly?Ala?Gly?Lys?Pro?Asp?Glu?Phe?Pro?Gln?Arg?Asn?Glu?Ile?Leu
75??????????????????80??????????????????85Asn?Met?Thr?Asp?Gly?Ile?Leu?Ser?Glu?Ser?Leu?Gln?Leu?Gly?Glu?Gly
90??????????????????95?????????????????100Gly?Lys?Ser?Arg?Val?Glu?Gly?Tyr?Thr?Asp?Phe?Gln?Tyr?Val?Arg?Ser
105?????????????????110?????????????????115Gly?Tyr?Ile?Tyr?Arg?Asn?Gly?Ala?Asn?Lys?Ile?Asp?Phe?Gln?Lys?Lys
120?????????????????125?????????????????130Ile?Ala?Leu?Ser?Gly?Pro?Asp?Gly?Tyr?Leu?Phe?Tyr?Lys?Gly?Ser?Asn135?????????????????140?????????????????145?????????????????150Pro?Ser?Gln?Ala?Leu?Pro?Met?Gly?Lys?Val?Gly?Tyr?Lys?Gly?Thr?Trp
155?????????????????160?????????????????165Asp?Tyr?Val?Thr?Asp?Ala?Lys?Met?Gly?Gln?Lys?Phe?Ser?Gln?Leu?Ala
170?????????????????175?????????????????180Gly?Phe?Pro?Ala?Gly?Asp?Arg?Tyr?Gly?Ala?Leu?Ser?Ala?Glu?Glu?Ala
185?????????????????190?????????????????195Asp?Val?Leu?Arg?Asn?Lys?Ser?Glu?Ala?Gln?Gln?Gly?Gln?Thr?Asp?Phe
200?????????????????205?????????????????210Gly?Leu?Thr?Ser?Glu?Phe?Glu?Val?Asp?Phe?Ala?Ala?Lys?Thr?Met?Thr215?????????????????220?????????????????225?????????????????230Gly?Ala?Leu?Tyr?Arg?Asn?Asn?Arg?Ile?Thr?Asn?Asn?Glu?Thr?Glu?Tyr
235?????????????????240?????????????????245Lys?Ala?Lys?Gln?Ile?Lys?Arg?Tyr?Asp?Ile?Gln?Ala?Asp?Leu?His?Gly
250?????????????????255?????????????????260Asn?Arg?Phe?Ser?Gly?Lys?Ala?Thr?Ala?Thr?Asp?Lys?Pro?Lys?Asn?Asp
265?????????????????270?????????????????275Glu?Thr?Lys?Glu?His?Pro?Phe?Val?Ser?Asp?Ser?Ser?Ser?Leu?Ser?Gly
280?????????????????285?????????????????290Gly?Phe?Phe?Gly?Pro?Lys?Gly?Glu?Glu?Leu?Gly?Phe?Arg?Phe?Leu?Ser295?????????????????300?????????????????305?????????????????310Asp?Asp?Gln?Lys?Val?Ala?Val?Val?Gly?Ser?Ala?Lys?Thr?Lys?Asp?Lys
315?????????????????320?????????????????325Leu?Glu?Asn?Gly?Ala?Ala?Ala?Ser?Gly?Ser?Thr?Gly?Ala?Ala?Ala?Ser
330?????????????????335?????????????????340Gly?Gly?Ala?Ala?Asp?Met?Pro?Ser?Glu?Asn?Gly?Lys?Leu?Thr?Thr?Val
345?????????????????350?????????????????355Leu?Asp?Ala?Ile?Glu?Leu?Lys?Ser?Gly?Gly?Lys?Glu?Val?Lys?Asn?Leu
360?????????????????365?????????????????370Asp?Asn?Phe?Ser?Asn?Ala?Ala?Gln?Leu?Val?Val?Asp?Gly?Ile?Met?Ile375?????????????????380?????????????????385?????????????????390Pro?Leu?Leu?Pro?Lys?Asn?Ser?Glu?Ser?Glu?Ser?Asn?Gln?Ala?Asp?Lys
395?????????????????400?????????????????405Gly?Lys?Asn?Gly?Gly?Thr?Ala?Phe?Thr?Arg?Lys?Phe?Glu?His?Thr?Pro
410?????????????????415?????????????????420Glu?Ser?Asp?Lys?Lys?Asp?Thr?Gln?Ala?Gly?Thr?Ala?Glu?Asn?Gly?Asn
425?????????????????430?????????????????435Pro?Ala?Ala?Ser?Asn?Thr?Ala?Gly?Asp?Thr?Asn?Gly?Lys?Thr?Lys?Thr
440?????????????????445?????????????????450Tyr?Glu?Val?Glu?Val?Cys?Cys?Ser?Asn?Leu?Asn?Tyr?Leu?Lys?Tyr?Gly455?????????????????460?????????????????465?????????????????470Met?Leu?Thr?Arg?Glu?Asn?Ser?Lys?Ser?Ala?Met?Gln?Ala?Gly?Glu?Asn
475?????????????????480?????????????????485Gly?Ser?Gln?Ala?Asp?Ala?Lys?Thr?Glu?Gln?Val?Glu?Gln?Ser?Met?Phe
490?????????????????495?????????????????500Leu?Gln?Gly?Glu?Arg?Thr?Asp?Glu?Lys?Glu?Ile?Pro?Lys?Glu?Gln?Gln
505?????????????????510?????????????????515Asp?Ile?Val?Tyr?Arg?Gly?Ser?Trp?Tyr?Gly?His?Ile?Ala?Asn?Asp?Thr
520?????????????????525?????????????????530Ser?Trp?Ser?Gly?Asn?Ala?Ser?Asp?Arg?Glu?Gly?Gly?Asn?Arg?Ala?Asp535?????????????????540?????????????????545?????????????????550Phe?Thr?Val?Asn?Phe?Gly?Thr?Lys?Lys?Ile?Asn?Gly?Thr?Leu?Thr?Ala
555?????????????????560?????????????????565Glu?Asn?Arg?Gln?Glu?Ala?Thr?Phe?Thr?Ile?Val?Gly?Asp?Ile?Lys?Asp
570?????????????????575?????????????????580Asn?Gly?Phe?Glu?Gly?Thr?Ala?Lys?Thr?Ala?Asp?Ser?Gly?Phe?Asp?His
585?????????????????590?????????????????595Asp?Gln?Ser?Asn?Thr?Thr?Arg?Thr?Pro?Lys?Ala?Tyr?Ile?Thr?Asp?Ala
600?????????????????605?????????????????610Lys?Val?Lys?Gly?Gly?Phe?Tyr?Gly?Pro?Lys?Ala?Glu?Glu?Leu?Gly?Gly615?????????????????620?????????????????625?????????????????630Trp?Phe?Ala?Tyr?Pro?Gly?Asp?Lys?Gln?Thr?Glu?Lys?Ala?Thr?Val?Thr
635?????????????????640?????????????????645Ser?Gly?Asp?Gly?Asn?Ser?Ala?Ser?Ser?Ala?Thr?Val?Val?Phe?Gly?Ala
650?????????????????655?????????????????660Lys?Arg?Gln?Lys?Pro?Val?Gln??*
665?????????????????670
(2) data of SEQIDNO:5:
(i) sequence signature:
(A) length: 2058 base pairs
(B) type: Nucleotide
(C) chain: two strands
(D) topology structure: linearity
(ii) molecule type: DNA (genome)
(vi) initial source:
(B) bacterial strain: meningitis naphthalene Se Shi coccus 90/94
(ix) feature:
(A) title/key: CDS
(B) position: 1..2058
(ix) feature:
(A) title/key: sig-peptide
(B) position: 1..48
(ix) feature:
(A) title/key: mat-peptide
(B) position: 49..2058
(ix) sequence description: SEQIDNO:5ATG GTA AAT CAG GCT GCT ATG GTG CTG CCT GTG TTT TTG TTG AGT GCT 48Met Val Asn Gln Ala Ala Met Val Leu Pro Val Phe Leu Leu Ser Ala-16-15-10-5TGT TTG GGC GGA GGC GGC AGT TTC GAT CTT GAT TCT GTC GAT ACC GAA 96Cys Leu Gly Gly Gly Gly Ser Phe Asp Leu Asp Ser Val Asp Thr Glu 15 10 15GCC CCG CGT CCC GCG CCA AAG TAT CAA GAT GTT TCT TCC GAA ACA CCG 144Ala Pro Arg Pro Ala Pro Lys Tyr Gln Asp Val Ser Ser Glu Thr Pro
20??????????????????25??????????????????30CAA?GCC?CAA?AAA?GAC?CAA?GGC?GGA?TAC?GGT?TTT?GCA?ATG?CGC?TTC?AAG??????????192Gln?Ala?Gln?Lys?Asp?Gln?Gly?Gly?Tyr?Gly?Phe?Ala?Met?Arg?Phe?Lys
35??????????????????40??????????????????45CGG?CGG?AAT?TGG?TAC?CCA?AAA?AAT?AAA?GAA?GAT?CAT?AAG?GCA?TTA?TCA????????240Arg?Arg?Asn?Trp?Tyr?Pro?Lys?Asn?Lys?Glu?Asp?His?Lys?Ala?Leu?Ser
50??????????????????55??????????????????60GAA?GCG?GAT?TGG?GAG?AAG?TTA?GGT?GCG?GGT?AAG?CCA?GAT?GAG?TTT?CCC????????288Glu?Ala?Asp?Trp?Glu?Lys?Leu?Gly?Ala?Gly?Lys?Pro?Asp?Glu?Phe?Pro?65??????????????????70??????????????????75??????????????????80CAA?AGG?AAT?GAA?ATA?TTG?AAT?ATG?ACT?GAC?GGA?ATT?CTG?AGT?GAG?TCT????????336Gln?Arg?Asn?Glu?Ile?Leu?Asn?Met?Thr?Asp?Gly?Ile?Leu?Ser?Glu?Ser
85??????????????????90??????????????????95CTT?CAG?CTG?GGT?GAG?GGC?GGC?AAA?AGC?CGC?GTA?GAA?GGA?TAC?ACG?GAT????????384Leu?Gln?Leu?Gly?Glu?Gly?Gly?Lys?Ser?Arg?Val?Glu?Gly?Tyr?Thr?Asp
100?????????????????105?????????????????110TTC?CAA?TAT?GTC?CGC?TCG?GGC?TAT?ATC?TAC?CGC?AAC?GGT?GTC?AAT?AAA????????432Phe?Gln?Tyr?Val?Arg?Ser?Gly?Tyr?Ile?Tyr?Arg?Asn?Gly?Val?Asn?Lys
115?????????????????120?????????????????125ATC?GAT?TCC?CAA?AAA?AAA?ATC?GCC?CTT?TCC?GGT?CCG?GAC?GGC?TAC?CTT????????480Ile?Asp?Ser?Gln?Lys?Lys?Ile?Ala?Leu?Ser?Gly?Pro?Asp?Gly?Tyr?Leu
130?????????????????135?????????????????140TTC?TAC?AAA?GGC?AGC?AAT?CCT?TCC?CAA?GCT?CTG?CCG?ACG?GGC?AAG?GCG????????528Phe?Tyr?Lys?Gly?Ser?Asn?Pro?Ser?Gln?Ala?Leu?Pro?Thr?Gly?Lys?Ala145?????????????????150?????????????????155?????????????????160ATT?TAC?AAA?GGT?ACT?TGG?GAT?TAT?GTA?ACC?GAT?GCC?AAG?GAA?AAA?CAG????????576Ile?Tyr?Lys?Gly?Thr?Trp?Asp?Tyr?Val?Thr?Asp?Ala?Lys?Glu?Lys?Gln
165?????????????????170?????????????????175AAG?TTT?CCC?CAG?TTG?GGT?AGT?TCT?CAA?GCG?GGG?GAT?AGG?TAC?GGG?GCT????????624Lys?Phe?Pro?Gln?Leu?Gly?Ser?Ser?Gln?Ala?Gly?Asp?Arg?Tyr?Gly?Ala
180?????????????????185?????????????????190CTG?TCT?GCC?GAG?GAA?GCG?GAT?GTG?TTG?CGC?AAC?AAA?AGC?GAG?GCA?CAG????????672Leu?Ser?Ala?Glu?Glu?Ala?Asp?Val?Leu?Arg?Asn?Lys?Ser?Glu?Ala?Gln
195?????????????????200?????????????????205CAA?GGT?CAG?ACC?GAT?TTC?GGG?CTG?ACC?AGC?GAG?TTT?GAG?GTG?GAT?TTC????????720Gln?Gly?Gln?Thr?Asp?Phe?Gly?Leu?Thr?Ser?Glu?Phe?Glu?Val?Asp?Phe
210?????????????????215?????????????????220GCC?GCC?AAG?ACC?ATG?ACC?GGC?GCG?CTC?TAC?CGC?AAT?AAC?CGG?ATT?ACT????????768Ala?Ala?Lys?Thr?Met?Thr?Gly?Ala?Leu?Tyr?Arg?Asn?Asn?Arg?Ile?Thr225?????????????????230?????????????????235?????????????????240AAT?AAC?GAA?ACC?GAA?AAT?AAA?GCC?AAA?CAA?ATT?AAA?CGT?TAC?GAC?ATT????????816Asn?Asn?Glu?Thr?Glu?Asn?Lys?Ala?Lys?Gln?Ile?Lys?Arg?Tyr?Asp?Ile
245?????????????????250?????????????????255CAG?GCT?GAC?CTG?CAC?GGT?AAC?CGC?TTC?AGC?GGC?AAG?GCA?ACG?GCA?ACC????????864Gln?Ala?Asp?Leu?His?Gly?Asn?Arg?Phe?Ser?Gly?Lys?Ala?Thr?Ala?Thr
260?????????????????265?????????????????270GAC?AAA?CCC?AAA?AAC?GAC?GAA?ACC?AAG?GAA?CAT?CCC?TTT?GTT?TCC?GAC?????????912Asp?Lys?Pro?Lys?Asn?Asp?Glu?Thr?Lys?Glu?His?Pro?Phe?Val?Ser?Asp
275?????????????????280?????????????????285TCG?TCT?TCT?TTG?AGC?GGC?GGC?TTT?TTC?GGT?CCG?AAG?GGT?GAG?GAA?TTG?????????960Ser?Ser?Ser?Leu?Ser?Gly?Gly?Phe?Phe?Gly?Pro?Lys?Gly?Glu?Glu?Leu
290?????????????????295?????????????????300GGT?TTC?CGC?TTT?TTG?AGC?GAC?GAT?CAA?AAA?GTT?GCC?GTT?GTC?GGC?AGC?????????1008Gly?Phe?Arg?Phe?Leu?Ser?Asp?Asp?Gln?Lys?Val?Ala?Val?Val?Gly?Ser305?????????????????310?????????????????315?????????????????320GCG?AAA?ACC?AAA?GAC?AAA?CTG?GAA?AAT?GGC?GCG?GCG?GCT?TCA?GGC?AGC?????????1056Ala?Lys?Thr?Lys?Asp?Lys?Leu?Glu?Asn?Gly?Ala?Ala?Ala?Ser?Gly?Ser
325?????????????????330?????????????????335ACA?GGT?GCG?GCA?GCA?TCG?GGC?GGT?GCG?GCA?GAT?ATG?CCG?TCT?GAA?AAC?????????1104Thr?Gly?Ala?Ala?Ala?Ser?Gly?Gly?Ala?Ala?Asp?Met?Pro?Ser?Glu?Asn
340?????????????????345?????????????????350GGT?AAG?CTG?ACC?ACG?GTT?TTG?GAT?GCG?GTT?GAG?CTG?AAA?TCT?GGC?GGT?????????1152Gly?Lys?Leu?Thr?Thr?Val?Leu?Asp?Ala?Val?Glu?Leu?Lys?Ser?Gly?Gly
355?????????????????360?????????????????365AAG?GAA?GTC?AAA?AAT?CTC?GAC?AAC?TTC?AGC?AAT?GCC?GCC?CAA?CTG?GTT?????????1200Lys?Glu?Val?Lys?Asn?Leu?Asp?Asn?Phe?Ser?Asn?Ala?Ala?Gln?Leu?Val
370?????????????????375?????????????????380GTC?GAC?GGC?ATT?ATG?ATT?CCG?CTC?CTG?CCC?AAG?GAT?TCC?GAA?AGC?GGG?????????1248Val?Asp?Gly?Ile?Met?Ile?Pro?Leu?Leu?Pro?Lys?Asp?Ser?Glu?Ser?Gly385?????????????????390?????????????????395?????????????????400AAC?AAT?CAG?GCA?GAT?AAA?GGT?AAA?AAC?GGC?GGA?ACA?GCC?TTT?ACC?CGC?????????1296Asn?Asn?Gln?Ala?Asp?Lys?Gly?Lys?Asn?Gly?Gly?Thr?Ala?Phe?Thr?Arg
405?????????????????410?????????????????415AAA?TTT?GAA?CAC?ACG?CCG?GAA?AGT?GAT?AAA?AAA?GAC?ACC?CAA?GCA?GGT?????????1344Lys?Phe?Glu?His?Thr?Pro?Glu?Ser?Asp?Lys?Lys?Asp?Thr?Gln?Ala?Gly
420?????????????????425?????????????????430ACG?GCG?GAG?AAT?GGC?AAT?CCA?GCC?GCT?TCA?AAT?ACG?GCA?GGT?GAT?ACC?????????1392Thr?Ala?Glu?Asn?Gly?Asn?Pro?Ala?Ala?Ser?Asn?Thr?Ala?Gly?Asp?Thr
435?????????????????440?????????????????445AAT?GGC?AAA?ACA?AAA?ACC?TAT?GAA?GTC?GAA?GTC?TGC?TGT?TCC?AAC?CTC?????????1440Asn?Gly?Lys?Thr?Lys?Thr?Tyr?Glu?Val?Glu?Val?Cys?Cys?Ser?Asn?Leu
450?????????????????455?????????????????460AAT?TAT?CTG?AAA?TAC?GGA?ATG?TTG?ACG?CGT?AAA?AAC?AGC?AAG?TCC?GCG?????????1488Asn?Tyr?Leu?Lys?Tyr?Gly?Met?Leu?Thr?Arg?Lys?Asn?Ser?Lys?Ser?Ala465?????????????????470?????????????????475?????????????????480ATG?CAG?GCA?GGC?GAA?AAC?GGT?AGT?CAA?GCT?GAC?GCT?AAA?ACG?GAA?CAA?????????1536Met?Gln?Ala?Gly?Glu?Asn?Gly?Ser?Gln?Ala?Asp?Ala?Lys?Thr?Glu?Gln
485?????????????????490?????????????????495GTT?GAA?CAA?AGT?ATG?TTC?CTC?CAA?GGC?GAG?CGC?ACC?GAT?GAA?AAA?GAG?????????1584Val?Glu?Gln?Ser?Met?Phe?Leu?Gln?Gly?Glu?Arg?Thr?Asp?Glu?Lys?Glu
500?????????????????505?????????????????510ATT?CCA?AAA?GAG?CAA?CAA?GAC?ATC?GTT?TAT?CGG?GGG?TCT?TGG?TAC?GGG?????????1632Ile?Pro?Lys?Glu?Gln?Gln?Asp?Ile?Val?Tyr?Arg?Gly?Ser?Trp?Tyr?Gly
515?????????????????520?????????????????525CAT?ATC?GCC?GGC?AGC?ACA?AGC?TGG?AGC?GGC?AAT?GCT?TCC?AAT?GCA?ACG?????????1680His?Ile?Ala?Gly?Ser?Thr?Ser?Trp?Ser?Gly?Asn?Ala?Ser?Asn?Ala?Thr
530?????????????????535?????????????????540AGT?GGC?AAC?AGG?GCG?GAA?TTT?ACT?GTG?AAT?TTC?GAT?ACG?AAA?AAA?ATT?????????1728Ser?Gly?Asn?Arg?Ala?Glu?Phe?Thr?Val?Asn?Phe?Asp?Thr?Lys?Lys?Ile545?????????????????550?????????????????555?????????????????560AAC?GGC?AAG?TTA?ACC?GCT?GAA?AAC?AGG?CAG?GAG?GCA?ACC?TTT?ACC?ATT?????????1776Asn?Gly?Lys?Leu?Thr?Ala?Glu?Asn?Arg?Gln?Glu?Ala?Thr?Phe?Thr?Ile
565?????????????????570?????????????????575GAG?GGA?ACG?ATT?CAG?GAC?AAC?GGC?TTT?GAA?GGT?ACG?GCA?AAA?ACT?GCT?????????1824Glu?Gly?Thr?Ile?Gln?Asp?Asn?Gly?Phe?Glu?Gly?Thr?Ala?Lys?Thr?Ala
580?????????????????585?????????????????590GAC?TTA?GGT?TTT?GAT?CTC?GAT?CAA?AGC?AAT?ACC?ACC?GGC?ACG?CCT?AAG?????????1872Asp?Leu?Gly?Phe?Asp?Leu?Asp?Gln?Ser?Asn?Thr?Thr?Gly?Thr?Pro?Lys
595?????????????????600?????????????????605GCA?TAT?ATC?ACA?AAC?GCC?AAG?GTG?CAG?GGC?GGT?TTT?TAC?GGG?CCT?AAA?????????1920Ala?Tyr?Ile?Thr?Asn?Ala?Lys?Val?Gln?Gly?Gly?Phe?Tyr?Gly?Pro?Lys
610?????????????????615?????????????????620GCC?GAA?GAG?TTG?GGC?GGA?TGG?TTT?GCC?TAT?TCG?GAC?GAT?AAA?CAA?ACG?????????1968Ala?Glu?Glu?Leu?Gly?Gly?Trp?Phe?Ala?Tyr?Ser?Asp?Asp?Lys?Gln?Thr625?????????????????630?????????????????635?????????????????640AAA?AAT?GCA?ACA?GAT?GCA?TCC?GGC?AAT?GGA?AAT?TCA?GCA?AGC?AGT?GCA??????????2016Lys?Asn?Ala?Thr?Asp?Ala?Ser?Gly?Asn?Gly?Asn?Ser?Ala?Ser?Ser?Ala
645?????????????????650?????????????????655ACT?GTC?GTA?TTC?GGT?GCG?AAA?CGC?CAA?CAG?CCT?GTG?CAA?TAA??????????????????2058Thr?Val?Val?Phe?Gly?Ala?Lys?Arg?Gln?Gln?Pro?Val?Gln??*
660?????????????????665?????????????????670
(2) data of SEQIDNO:6:
(i) sequence signature:
(A) length: 686 amino acid
(B) type: amino acid
(D) topology structure: linearity
(ii) molecule type: protein
(ix) sequence description: SEQIDNO:6:Met Val Asn Gln Ala Ala Met Val Leu Pro Val Phe Leu Leu Ser Ala-16-15-10-5Cys Leu Gly Gly Gly Gly Ser Phe Asp Leu Asp Ser Val Asp Thr Glu, 15 10 15Ala Pro Arg Pro Ala Pro Lys Tyr Gln Asp Val Ser Ser Glu Thr Pro
20??????????????????25??????????????????30Gln?Ala?Gln?Lys?Asp?Gln?Gly?Gly?Tyr?Gly?Phe?Ala?Met?Arg?Phe?Lys
35??????????????????40??????????????????45Arg?Arg?Asn?Trp?Tyr?Pro?Lys?Asn?Lys?Glu?Asp?His?Lys?Ala?Leu?Ser
50??????????????????55??????????????????60Glu?Ala?Asp?Trp?Glu?Lys?Leu?Gly?Ala?Gly?Lys?Pro?Asp?Glu?Phe?Pro?65??????????????????70??????????????????75??????????????????80Gln?Arg?Asn?Glu?Ile?Leu?Asn?Met?Thr?Asp?Gly?Ile?Leu?Ser?Glu?Ser
85??????????????????90??????????????????95Leu?Gln?Leu?Gly?Glu?Gly?Gly?Lys?Ser?Arg?Val?Glu?Gly?Tyr?Thr?Asp
100?????????????????105?????????????????110Phe?Gln?Tyr?Val?Arg?Ser?Gly?Tyr?Ile?Tyr?Arg?Asn?Gly?Val?Asn?Lys
115?????????????????120?????????????????125Ile?Asp?Ser?Gln?Lys?Lys?Ile?Ala?Leu?Ser?Gly?Pro?Asp?Gly?Tyr?Leu
130?????????????????135?????????????????140Phe?Tyr?Lys?Gly?Ser?Asn?Pro?Ser?Gln?Ala?Leu?Pro?Thr?Gly?Lys?Ala145?????????????????150?????????????????155?????????????????160Ile?Tyr?Lys?Gly?Thr?Trp?Asp?Tyr?Val?Thr?Asp?Ala?Lys?Glu?Lys?Gln
165?????????????????170?????????????????175Lys?Phe?Pro?Gln?Leu?Gly?Ser?Ser?Gln?Ala?Gly?Asp?Arg?Tyr?Gly?Ala
180?????????????????185?????????????????190Leu?Ser?Ala?Glu?Glu?Ala?Asp?Val?Leu?Arg?Asn?Lys?Ser?Glu?Ala?Gln
195?????????????????200?????????????????205Gln?Gly?Gln?Thr?Asp?Phe?Gly?Leu?Thr?Ser?Glu?Phe?Glu?Val?Asp?Phe
210?????????????????215?????????????????220Ala?Ala?Lys?Thr?Met?Thr?Gly?Ala?Leu?Tyr?Arg?Asn?Asn?Arg?Ile?Thr225?????????????????230?????????????????235?????????????????240Asn?Asn?Glu?Thr?Glu?Asn?Lys?Ala?Lys?Gln?Ile?Lys?Arg?Tyr?Asp?Ile
245?????????????????250?????????????????255Gln?Ala?Asp?Leu?His?Gly?Asn?Arg?Phe?Ser?Gly?Lys?Ala?Thr?Ala?Thr
260?????????????????265?????????????????270Asp?Lys?Pro?Lys?Asn?Asp?Glu?Thr?Lys?Glu?His?Pro?Phe?Val?Ser?Asp
275?????????????????280?????????????????285Ser?Ser?Ser?Leu?Ser?Gly?Gly?Phe?Phe?Gly?Pro?Lys?Gly?Glu?Glu?Leu
290?????????????????295?????????????????300Gly?Phe?Arg?Phe?Leu?Ser?Asp?Asp?Gln?Lys?Val?Ala?Val?Val?Gly?Ser305?????????????????310?????????????????315?????????????????320Ala?Lys?Thr?Lys?Asp?Lys?Leu?Glu?Asn?Gly?Ala?Ala?Ala?Ser?Gly?Ser
325?????????????????330?????????????????335Thr?Gly?Ala?Ala?Ala?Ser?Gly?Gly?Ala?Ala?Asp?Met?Pro?Ser?Glu?Asn
340?????????????????345?????????????????350Gly?Lys?Leu?Thr?Thr?Val?Leu?Asp?Ala?Val?Glu?Leu?Lys?Ser?Gly?Gly
355?????????????????360?????????????????365Lys?Glu?Val?Lys?Asn?Leu?Asp?Asn?Phe?Ser?Asn?Ala?Ala?Gln?Leu?Val
370?????????????????375?????????????????380Val?Asp?Gly?Ile?Met?Ile?Pro?Leu?Leu?Pro?Lys?Asp?Ser?Glu?Ser?Gly385?????????????????390?????????????????395?????????????????400Asn?Asn?Gln?Ala?Asp?Lys?Gly?Lys?Asn?Gly?Gly?Thr?Ala?Phe?Thr?Arg
405?????????????????410?????????????????415Lys?Phe?Glu?His?Thr?Pro?Glu?Ser?Asp?Lys?Lys?Asp?Thr?Gln?Ala?Gly
420?????????????????425?????????????????430Thr?Ala?Glu?Asn?Gly?Asn?Pro?Ala?Ala?Ser?Asn?Thr?Ala?Gly?Asp?Thr
435?????????????????440?????????????????445Asn?Gly?Lys?Thr?Lys?Thr?Tyr?Glu?Val?Glu?Val?Cys?Cys?Ser?Asn?Leu
450?????????????????455?????????????????460Asn?Tyr?Leu?Lys?Tyr?Gly?Met?Leu?Thr?Arg?Lys?Asn?Ser?Lys?Ser?Ala465?????????????????470????????????????475??????????????????480Met?Gln?Ala?Gly?Glu?Asn?Gly?Ser?Gln?Ala?Asp?Ala?Lys?Thr?Glu?Gln
485?????????????????490?????????????????495Val?Glu?Gln?Ser?Met?Phe?Leu?Gln?Gly?Glu?Arg?Thr?Asp?Glu?Lys?Glu
500?????????????????505?????????????????510Ile?Pro?Lys?Glu?Gln?Gln?Asp?Ile?Val?Tyr?Arg?Gly?Ser?Trp?Tyr?Gly
515?????????????????520?????????????????525His?Ile?Ala?Gly?Ser?Thr?Ser?Trp?Ser?Gly?Asn?Ala?Ser?Asn?Ala?Thr
530?????????????????535?????????????????540Ser?Gly?Asn?Arg?Ala?Glu?Phe?Thr?Val?Asn?Phe?Asp?Thr?Lys?Lys?Ile545?????????????????550?????????????????555?????????????????560Asn?Gly?Lys?Leu?Thr?Ala?Glu?Asn?Arg?Gln?Glu?Ala?Thr?Phe?Thr?Ile
565?????????????????570?????????????????575Glu?Gly?Thr?Ile?Gln?Asp?Asn?Gly?Phe?Glu?Gly?Thr?Ala?Lys?Thr?Ala
580?????????????????585?????????????????590Asp?Leu?Gly?Phe?Asp?Leu?Asp?Gln?Ser?Asn?Thr?Thr?Gly?Thr?Pro?Lys
595?????????????????600?????????????????605Ala?Tyr?Ile?Thr?Asn?Ala?Lys?Val?Gln?Gly?Gly?Phe?Tyr?Gly?Pro?Lys
610?????????????????615?????????????????620Ala?Glu?Glu?Leu?Gly?Gly?Trp?Phe?Ala?Tyr?Ser?Asp?Asp?Lys?Gln?Thr625?????????????????630?????????????????635?????????????????640Lys?Asn?Ala?Thr?Asp?Ala?Ser?Gly?Asn?Gly?Asn?Ser?Ala?Ser?Ser?Ala
645?????????????????650?????????????????655Thr?Val?Val?Phe?Gly?Ala?Lys?Arg?Gln?Gln?Pro?Val?Gln??*
660??????????????????665?????????????????670
(2) data of SEQIDNO:7:
(i) sequence signature:
(A) length: 2230 base pairs
(B) type: Nucleotide
(C) chain: strand
(D) topology structure: linearity
(ii) molecule type: DNA (genome)
(vi) initial source:
(A) organism: meningitis naphthalene Se Shi coccus
(B) bacterial strain: IM2169
(ix) feature:
(A) title/key: sig-peptide
(B) position: 60..119
(ix) feature:
(A) title/key: mat-peptide
(B) position: 120..2192
(ix) feature:
(A) title/key: CDS
(B) position: 60..2192
(ix) feature:
(A) title/key: misc-feature
(B) position: 120..1154
(ix) feature:
(A) title/key: misc-feature
(B) position: 1155..1748
(ix) feature:
(A) title/key: misc-feature
(B) position: 1749..2192
(ix) feature:
(A) title/key: misc-feature
(B) position: 237..1169
(ix) sequence description: SEQIDNO:7ATTTGTTAAA AATAAATAAA ATAATAATCC TTATCATTCT TTAATTGAAT TGGGTTTAT 59ATG AAC AAT CCA TTG GTA AAT CAG GCT GCT ATG GTG CTG CCT GTG TTT 107Met Asn Asn Pro Leu Val Asn Gln Ala Ala Met Val Leu Pro Val Phe-20-15-10-5TTG TTG AGT GCC TGT CTG GGC GGC GGC GGC AGT TTC GAT CTT GAT TCT 155Leu Leu Ser Ala Cys Leu Gly Gly Gly Gly Ser Phe Asp Leu Asp Ser
1???????????????5??????????????????10GTC?GAT?ACC?GAA?GCC?CCG?CGT?CCC?GCG?CCA?AAG?TAT?CAA?GAT?GTT?TCT????????203Val?Asp?Thr?Glu?Ala?Pro?Arg?Pro?Ala?Pro?Lys?Tyr?Gln?Asp?Val?Ser
15??????????????????20??????????????????25TCC?GAA?AAA?CCG?CAA?GCC?CAA?AAA?GAC?CAA?GGC?GGA?TAC?GGT?TTT?GCG????????251Ser?Glu?Lys?Pro?Gln?Ala?Gln?Lys?Asp?Gln?Gly?Gly?Tyr?Gly?Phe?Ala
30??????????????????35??????????????????40ATG?AGG?TTG?AAA?CGG?AGG?AAT?TGG?TAT?CCG?GGG?GCA?GAA?GAA?AGC?GAG????????299Met?Arg?Leu?Lys?Arg?Arg?Asn?Trp?Tyr?Pro?Gly?Ala?Glu?Glu?Ser?Glu?45??????????????????50??????????????????55??????????????????60GTT?AAA?CTG?AAC?GAG?AGT?GAT?TGG?GAG?GCG?ACG?GGA?TTG?CCG?ACA?AAA????????347Val?Lys?Leu?Asn?Glu?Ser?Asp?Trp?Glu?Ala?Thr?Gly?Leu?Pro?Thr?Lys
65??????????????????70??????????????????75CCC?AAG?GAA?CTT?CCT?AAA?CGG?CAA?AAA?TCG?GTT?ATT?GAA?AAA?GTA?GAA????????395Pro?Lys?Glu?Leu?Pro?Lys?Arg?Gln?Lys?Ser?Val?Ile?Glu?Lys?Val?Glu
80??????????????????85??????????????????90ACA?GAC?GGC?GAC?AGC?GAT?ATT?TAT?TCT?TCC?CCC?TAT?CTC?ACA?CCA?TCA????????443Thr?Asp?Gly?Asp?Ser?Asp?Ile?Tyr?Ser?Ser?Pro?Tyr?Leu?Thr?Pro?Ser
95?????????????????100?????????????????105AAC?CAT?CAA?AAC?GGC?AGC?GCT?GGC?AAC?GGT?GTA?AAT?CAA?CCT?AAA?AAT????????491Asn?His?Gln?Asn?Gly?Ser?Ala?Gly?Asn?Gly?Val?Asn?Gln?Pro?Lys?Asn
110?????????????????115?????????????????120CAG?GCA?ACA?GGT?CAC?GAA?AAT?TTC?CAA?TAT?GTT?TAT?TCC?GGT?TGG?TTT????????539Gln?Ala?Thr?Gly?His?Glu?Asn?Phe?Gln?Tyr?Val?Tyr?Ser?Gly?Trp?Phe125?????????????????130?????????????????135?????????????????140TAT?AAA?CAT?GCA?GCG?AGT?GAA?AAA?GAT?TTC?AGT?AAC?AAA?AAA?ATT?AAG????????587Tyr?Lys?His?Ala?Ala?Ser?Glu?Lys?Asp?Phe?Ser?Asn?Lys?Lys?Ile?Lys
145?????????????????150?????????????????155TCA?GGC?GAC?GAT?GGT?TAT?ATC?TTC?TAT?CAC?GGT?GAA?AAA?CCT?TCC?CGA????????635Ser?Gly?Asp?Asp?Gly?Tyr?Ile?Phe?Tyr?His?Gly?Glu?Lys?Pro?Ser?Arg
160?????????????????165?????????????????170CAA?CTT?CCT?GCT?TCT?GGA?AAA?GTT?ATC?TAC?AAA?GGT?GTG?TGG?CAT?TTT????????683Gln?Leu?Pro?Ala?Ser?Gly?Lys?Val?Ile?Tyr?Lys?Gly?Val?Trp?His?Phe
175?????????????????180?????????????????185GTA?ACC?GAT?ACA?AAA?AAG?GGT?CAA?GAT?TTT?CGT?GAA?ATT?ATC?CAG?CCT????????731Val?Thr?Asp?Thr?Lys?Lys?Gly?Gln?Asp?Phe?Arg?Glu?Ile?Ile?Gln?Pro
190?????????????????195?????????????????200TCA?AAA?AAA?CAA?GGC?GAC?AGG?TAT?AGC?GGA?TTT?TCT?GGT?GAT?GGC?AGC????????779Ser?Lys?Lys?Gln?Gly?Asp?Arg?Tyr?Ser?Gly?Phe?Ser?Gly?Asp?Gly?Ser205?????????????????210?????????????????215?????????????????220GAA?GAA?TAT?TCC?AAC?AAA?AAC?GAA?TCC?ACG?CTG?AAA?GAT?GAT?CAC?GAG????????827Glu?Glu?Tyr?Ser?Asn?Lys?Asn?Glu?Ser?Thr?Leu?Lys?Asp?Asp?His?Glu
225?????????????????230?????????????????235GGT?TAT?GGT?TTT?ACC?TCG?AAT?TTA?GAA?GTG?GAT?TTC?GGC?AAT?AAG?AAA????????875Gly?Tyr?Gly?Phe?Thr?Ser?Asn?Leu?Glu?Val?Asp?Phe?Gly?Asn?Lys?Lys
240?????????????????245?????????????????250TTG?ACG?GGT?AAA?TTA?ATA?CGC?AAT?AAT?GCG?AGC?CTA?AAT?AAT?AAT?ACT????????923Leu?Thr?Gly?Lys?Leu?Ile?Arg?Asn?Asn?Ala?Ser?Leu?Asn?Asn?Asn?Thr
255?????????????????260?????????????????265AAT?AAT?GAC?AAA?CAT?ACC?ACC?CAA?TAC?TAC?AGC?CTT?GAT?GCA?CAA?ATA????????971Asn?Asn?Asp?Lys?His?Thr?Thr?Gln?Tyr?Tyr?Ser?Leu?Asp?Ala?Gln?Ile
270?????????????????275?????????????????280ACA?GGC?AAC?CGC?TTC?AAC?GGC?ACG?GCA?ACG?GCA?ACT?GAC?AAA?AAA?GAG???????1019Thr?Gly?Asn?Arg?Phe?Asn?Gly?Thr?Ala?Thr?Ala?Thr?Asp?Lys?Lys?Glu285?????????????????290?????????????????295?????????????????300AAT?GAA?ACC?AAA?CTA?CAT?CCC?TTT?GTT?TCC?GAC?TCG?TCT?TCT?TTG?AGC???????1067Asn?Glu?Thr?Lys?Leu?His?Pro?Phe?Val?Ser?Asp?Ser?Ser?Ser?Leu?Ser
305?????????????????310?????????????????315GGC?GGC?TTT?TTC?GGC?CCG?CAG?GGT?GAG?GAA?TTG?GGT?TTC?CGC?TTT?TTG???????1115Gly?Gly?Phe?Phe?Gly?Pro?Gln?Gly?Glu?Glu?Leu?Gly?Phe?Arg?Phe?Leu
320?????????????????325?????????????????330AGC?GAC?GAT?CAA?AAA?GTT?GCC?GTT?GTC?GGC?AGC?GCG?AAA?ACC?AAA?GAC???????1163Ser?Asp?Asp?Gln?Lys?Val?Ala?Val?Val?Gly?Ser?Ala?Lys?Thr?Lys?Asp
335?????????????????340?????????????????345AAA?CTG?GAA?AAT?GGC?GCG?GCG?GCT?TCA?GGC?AGC?ACA?GGT?GCG?GCA?GCA???????1211Lys?Leu?Glu?Asn?Gly?Ala?Ala?Ala?Ser?Gly?Ser?Thr?Gly?Ala?Ala?Ala
350?????????????????355?????????????????360TCG?GGC?GGT?GCG?GCA?GGC?ACG?TCG?TCT?GAA?AAC?AGT?AAG?CTG?ACC?ACG???????1259Ser?Gly?Gly?Ala?Ala?Gly?Thr?Ser?Ser?Glu?Asn?Ser?Lys?Leu?Thr?Thr365?????????????????370?????????????????375?????????????????380GTT?TTG?GAT?GCG?GTT?GAA?TTG?ACA?CTA?AAC?GAC?AAG?AAA?ATC?AAA?AAT???????1307Val?Leu?Asp?Ala?Val?Glu?Leu?Thr?Leu?Asn?Asp?Lys?Lys?Ile?Lys?Asn
385?????????????????390?????????????????395CTC?GAC?AAC?TTC?AGC?AAT?GCC?GCC?CAA?CTG?GTT?GTC?GAC?GGC?ATT?ATG???????1355Leu?Asp?Asn?Phe?Ser?Asn?Ala?Ala?Gln?Leu?Val?Val?Asp?Gly?Ile?Met
400?????????????????405?????????????????410ATT?CCG?CTC?CTG?CCC?AAG?GAT?TCC?GAA?AGC?GGG?AAC?ACT?CAG?GCA?GAT???????1403Ile?Pro?Leu?Leu?Pro?Lys?Asp?Ser?Glu?Ser?Gly?Asn?Thr?Gln?Ala?Asp
415?????????????????420?????????????????425AAA?GGT?AAA?AAC?GGC?GGA?ACA?GAA?TTT?ACC?CGC?AAA?TTT?GAA?CAC?ACG???????1451Lys?Gly?Lys?Asn?Gly?Gly?Thr?Glu?Phe?Thr?Arg?Lys?Phe?Glu?His?Thr
430?????????????????435?????????????????440CCG?GAA?AGT?GAT?AAA?AAA?GAC?GCC?CAA?GCA?GGT?ACG?CAG?ACG?AAT?GGG???????1499Pro?Glu?Ser?Asp?Lys?Lys?Asp?Ala?Gln?Ala?Gly?Thr?Gln?Thr?Asn?Gly445?????????????????450?????????????????455?????????????????460GCG?CAA?ACC?GCT?TCA?AAT?ACG?GCA?GGT?GAT?ACC?AAT?GGC?AAA?ACA?AAA???????1547Ala?Gln?Thr?Ala?Ser?Asn?Thr?Ala?Gly?Asp?Thr?Asn?Gly?Lys?Thr?Lys
465?????????????????470?????????????????475ACC?TAT?GAA?GTC?GAA?GTC?TGC?TGT?TCC?AAC?CTC?AAT?TAT?CTG?AAA?TAC???????1595Thr?Tyr?Glu?Val?Glu?Val?Cys?Cys?Ser?Asn?Leu?Asn?Tyr?Leu?Lys?Tyr
480?????????????????485?????????????????490GGA?ATG?TTG?ACG?CGC?AAA?AAC?AGC?AAG?TCC?GCG?ATG?CAG?GCA?GGA?GGA???????1643Gly?Met?Leu?Thr?Arg?Lys?Asn?Ser?Lys?Ser?Ala?Met?Gln?Ala?Gly?Gly
495?????????????????500?????????????????505AAC?AGT?AGT?CAA?GCT?GAT?GCT?AAA?ACG?GAA?CAA?GTT?GAA?CAA?AGT?ATG???????1691Asn?Ser?Ser?Gln?Ala?Asp?Ala?Lye?Thr?Glu?Gln?Val?Glu?Gln?Ser?Met
510?????????????????515?????????????????520TTC?CTC?CAA?GGC?GAG?CGT?ACC?GAT?GAA?AAA?GAG?ATT?CCA?ACC?GAC?CAA???????1739Phe?Leu?Gln?Gly?Glu?Arg?Thr?Asp?Glu?Lys?Glu?Ile?Pro?Thr?Asp?Gln525?????????????????530?????????????????535?????????????????540AAC?GTC?GTT?TAT?CGG?GGG?TCT?TGG?TAC?GGG?CAT?ATT?GCC?AAC?GGC?ACA???????1787Asn?Val?Val?Tyr?Arg?Gly?Ser?Trp?Tyr?Gly?His?Ile?Ala?Asn?Gly?Thr
545?????????????????550?????????????????555AGC?TGG?AGC?GGC?AAT?GCT?TCT?GAT?AAA?GAG?GGC?GGC?AAC?AGG?GCG?GAA???????1835Ser?Trp?Ser?Gly?Asn?Ala?Ser?Asp?Lys?Glu?Gly?Gly?Asn?Arg?Ala?Glu
560?????????????????565?????????????????570TTT?ACT?GTG?AAT?TTT?GCC?GAT?AAA?AAA?ATT?ACC?GGC?AAG?TTA?ACC?GCT???????1883Phe?Thr?Val?Asn?Phe?Ala?Asp?Lys?Lys?Ile?Thr?Gly?Lys?Leu?Thr?Ala
575?????????????????580?????????????????585GAA?AAC?AGG?CAG?GCG?CAA?ACC?TTT?ACC?ATT?GAG?GGA?ATG?ATT?CAG?GGC???????1931Glu?Asn?Arg?Gln?Ala?Gln?Thr?Phe?Thr?Ile?Glu?Gly?Met?Ile?Gln?Gly
590?????????????????595?????????????????600AAC?GGC?TTT?GAA?GGT?ACG?GCG?AAA?ACT?GCT?GAG?TCA?GGT?TTT?GAT?CTC???????1979Asn?Gly?Phe?Glu?Gly?Thr?Ala?Lys?Thr?Ala?Glu?Ser?Gly?Phe?Asp?Leu605?????????????????610?????????????????615?????????????????620GAT?CAA?AAA?AAT?ACC?ACC?CGC?ACG?CCT?AAG?GCA?TAT?ATC?ACA?GAT?GCC???????2027Asp?Gln?Lys?Asn?Thr?Thr?Arg?Thr?Pro?Lys?Ala?Tyr?Ile?Thr?Asp?Ala
625?????????????????630?????????????????635AAG?GTA?AAG?GGC?GGT?TTT?TAC?GGG?CCT?AAA?GCC?GAA?GAG?TTG?GGC?GGA???????2075Lys?Val?Lys?Gly?Gly?Phe?Tyr?Gly?Pro?Lys?Ala?Glu?Glu?Leu?Gly?Gly
640?????????????????645?????????????????650TGG?TTT?GCC?TAT?CCG?GGC?GAT?AAA?CAA?ACG?GAA?AAG?GCA?ACA?GCT?ACA???????2123Trp?Phe?Ala?Tyr?Pro?Gly?Asp?Lys?Gln?Thr?Glu?Lys?Ala?Thr?Ala?Thr
655?????????????????660?????????????????665TCC?AGC?GAT?GGA?AAT?TCA?GCA?AGC?AGC?GCG?ACC?GTG?GTA?TTC?GGT?GCG???????2171Ser?Ser?Asp?Gly?Asn?Ser?Ala?Ser?Ser?Ala?Thr?Val?Val?Phe?Gly?Ala
670?????????????????675?????????????????680AAA?CGC?CAA?CAG?CCT?GTG?CAA?TAAGCACGGT?TGCCGAACAA?TCAAGAATAA??????????2222Lys?Arg?Gln?Gln?Pro?Val?Gln685?????????????????690GGCTTCAG??????????????????????????????????????????????????????????????2230
2) data of SEQIDNO:8:
(i) sequence signature:
(A) length: 711 amino acid
(B) type: amino acid
(D) topology structure: linearity
(ii) molecule type: protein
(ix) sequence description: SEQIDNO:8:Met Asn Asn Pro Leu Val Asn Gln Ala Ala Met Val Leu Pro Val Phe-20-15-10-5Leu Leu Ser Ala Cys Leu Gly Gly Gly Gly Ser Phe Asp Leu Asp Ser
1???????????????5??????????????????10Val?Asp?Thr?Glu?Ala?Pro?Arg?Pro?Ala?Pro?Lys?Tyr?Gln?Asp?Val?Ser
15??????????????????20??????????????????25Ser?Glu?Lys?Pro?Gln?Ala?Gln?Lys?Asp?Gln?Gly?Gly?Tyr?Gly?Phe?Ala
30??????????????????35??????????????????40Met?Arg?Leu?Lys?Arg?Arg?Asn?Trp?Tyr?Pro?Gly?Ala?Glu?Glu?Ser?Glu?45??????????????????50??????????????????55??????????????????60Val?Lys?Leu?Asn?Glu?Ser?Asp?Trp?Glu?Ala?Thr?Gly?Leu?Pro?Thr?Lys
65??????????????????70??????????????????75Pro?Lys?Glu?Leu?Pro?Lys?Arg?Gln?Lys?Ser?Val?Ile?Glu?Lys?Val?Glu
80??????????????????85??????????????????90Thr?Asp?Gly?Asp?Ser?Asp?Ile?Tyr?Ser?Ser?Pro?Tyr?Leu?Thr?Pro?Ser
95?????????????????100?????????????????105Asn?His?Gln?Asn?Gly?Ser?Ala?Gly?Asn?Gly?Val?Asn?Gln?Pro?Lys?Asn
110?????????????????115?????????????????120Gln?Ala?Thr?Gly?His?Glu?Asn?Phe?Gln?Tyr?Val?Tyr?Ser?Gly?Trp?Phe125?????????????????130?????????????????135?????????????????140Tyr?Lys?His?Ala?Ala?Ser?Glu?Lys?Asp?Phe?Ser?Asn?Lys?Lys?Ile?Lys
145?????????????????150?????????????????155Ser?Gly?Asp?Asp?Gly?Tyr?Ile?Phe?Tyr?His?Gly?Glu?Lys?Pro?Ser?Arg
160?????????????????165?????????????????170Gln?Leu?Pro?Ala?Ser?Gly?Lys?Val?Ile?Tyr?Lys?Gly?Val?Trp?His?Phe
175?????????????????180?????????????????185Val?Thr?Asp?Thr?Lys?Lys?Gly?Gln?Asp?Phe?Arg?Glu?Ile?Ile?Gln?Pro
190?????????????????195?????????????????200Ser?Lys?Lys?Gln?Gly?Asp?Arg?Tyr?Ser?Gly?Phe?Ser?Gly?Asp?Gly?Ser205?????????????????210?????????????????215?????????????????220Glu?Glu?Tyr?Ser?Asn?Lys?Asn?Glu?Ser?Thr?Leu?Lys?Asp?Asp?His?Glu
225?????????????????230?????????????????235Gly?Tyr?Gly?Phe?Thr?Ser?Asn?Leu?Glu?Val?Asp?Phe?Gly?Asn?Lys?Lys
240?????????????????245?????????????????250Leu?Thr?Gly?Lys?Leu?Ile?Arg?Asn?Asn?Ala?Ser?Leu?Asn?Asn?Asn?Thr
255?????????????????260?????????????????265Asn?Asn?Asp?Lys?His?Thr?Thr?Gln?Tyr?Tyr?Ser?Leu?Asp?Ala?Gln?Ile
270?????????????????275?????????????????280Thr?Gly?Asn?Arg?Phe?Asn?Gly?Thr?Ala?Thr?Ala?Thr?Asp?Lys?Lys?Glu285?????????????????290?????????????????295?????????????????300Asn?Glu?Thr?Lys?Leu?His?Pro?Phe?Val?Ser?Asp?Ser?Ser?Ser?Leu?Ser
305?????????????????310?????????????????315Gly?Gly?Phe?Phe?Gly?Pro?Gln?Gly?Glu?Glu?Leu?Gly?Phe?Arg?Phe?Leu
320?????????????????325?????????????????330Ser?Asp?Asp?Gln?Lys?Val?Ala?Val?Val?Gly?Ser?Ala?Lys?Thr?Lys?Asp
335?????????????????340?????????????????345Lys?Leu?Glu?Asn?Gly?Ala?Ala?Ala?Ser?Gly?Ser?Thr?Gly?Ala?Ala?Ala
350?????????????????355?????????????????360Ser?Gly?Gly?Ala?Ala?Gly?Thr?Ser?Ser?Glu?Asn?Ser?Lys?Leu?Thr?Thr365?????????????????370?????????????????375?????????????????380Val?Leu?Asp?Ala?Val?Glu?Leu?Thr?Leu?Asn?Asp?Lys?Lys?Ile?Lys?Asn
385?????????????????390?????????????????395Leu?Asp?Asn?Phe?Ser?Asn?Ala?Ala?Gln?Leu?Val?Val?Asp?Gly?Ile?Met
400?????????????????405?????????????????410Ile?Pro?Leu?Leu?Pro?Lys?Asp?Ser?Glu?Ser?Gly?Asn?Thr?Gln?Ala?Asp
415?????????????????420?????????????????425Lys?Gly?Lys?Asn?Gly?Gly?Thr?Glu?Phe?Thr?Arg?Lys?Phe?Glu?His?Thr
430?????????????????435?????????????????440Pro?Glu?Ser?Asp?Lys?Lys?Asp?Ala?Gln?Ala?Gly?Thr?Gln?Thr?Asn?Gly445?????????????????450?????????????????455?????????????????460Ala?Gln?Thr?Ala?Ser?Asn?Thr?Ala?Gly?Asp?Thr?Asn?Gly?Lys?Thr?Lys
465?????????????????470?????????????????475Thr?Tyr?Glu?Val?Glu?Val?Cys?Cys?Ser?Asn?Leu?Asn?Tyr?Leu?Lys?Tyr
480?????????????????485?????????????????490Gly?Met?Leu?Thr?Arg?Lys?Asn?Ser?Lys?Ser?Ala?Met?Gln?Ala?Gly?Gly
495?????????????????500?????????????????505Asn?Ser?Ser?Gln?Ala?Asp?Ala?Lys?Thr?Glu?Gln?Val?Glu?Gln?Ser?Met
510?????????????????515?????????????????520Phe?Leu?Gln?Gly?Glu?Arg?Thr?Asp?Glu?Lys?Glu?Ile?Pro?Thr?Asp?Gln525?????????????????530?????????????????535?????????????????540Asn?Val?Val?Tyr?Arg?Gly?Ser?Trp?Tyr?Gly?His?Ile?Ala?Asn?Gly?Thr
545?????????????????550?????????????????555Ser?Trp?Ser?Gly?Asn?Ala?Ser?Asp?Lys?Glu?Gly?Gly?Asn?Arg?Ala?Glu
560?????????????????565?????????????????570Phe?Thr?Val?Asn?Phe?Ala?Asp?Lys?Lys?Ile?Thr?Gly?Lys?Leu?Thr?Ala
575?????????????????580?????????????????585Glu?Asn?Arg?Gln?Ala?Gln?Thr?Phe?Thr?Ile?Glu?Gly?Met?Ile?Gln?Gly
590?????????????????595?????????????????600Asn?Gly?Phe?Glu?Gly?Thr?Ala?Lys?Thr?Ala?Glu?Ser?Gly?Phe?Asp?Leu605?????????????????610?????????????????615?????????????????620Asp?Gln?Lys?Asn?Thr?Thr?Arg?Thr?Pro?Lys?Ala?Tyr?Ile?Thr?Asp?Ala
625?????????????????630?????????????????635Lys?Val?Lys?Gly?Gly?Phe?Tyr?Gly?Pro?Lys?Ala?Glu?Glu?Leu?Gly?Gly
640?????????????????645?????????????????650Trp?Phe?Ala?Tyr?Pro?Gly?Asp?Lys?Gln?Thr?Glu?Lys?Ala?Thr?Ala?Thr
655?????????????????660?????????????????665Ser?Ser?Asp?Gly?Asn?Ser?Ala?Ser?Ser?Ala?Thr?Val?Val?Phe?Gly?Ala
670?????????????????675?????????????????680Lys?Arg?Gln?Gln?Pro?Val?Gln685?????????????????690
2) data of SEQIDNO:9:
(i) sequence signature:
(A) length: 2064 base pairs
(B) type: Nucleotide
(C) chain: strand
(D) topology structure: linearity
(ii) molecule type: DNA (genome)
(vi) initial source:
(A) organism: meningitis naphthalene Se Shi coccus
(B) bacterial strain: 8680
(ix) feature:
(A) title/key: CDS
(B) position: 1..2061
(ix) feature:
(A) title/key: sig-peptide
(B) position: 1..30
(ix) feature:
(A) title/key: mat-peptide
(B) position: 31..2061
(ix) sequence description: SEQIDNO:9ATG GTG CTG CCT GTG TTT TTG TCG AGT GCT TGT CTG GGC GGA GGC GGC 48Met Val Leu Pro Val Phe Leu Ser Ser Ala Cys Leu Gly Gly Gly Gly-10-5 1 5GGC AGT TTC GAT CTT GAT TCT GTC GAT ACC GAA GCC CCG CGT CCC GCG 96Gly Ser Phe Asp Leu Asp Ser Val Asp Thr Glu Ala Pro Arg Pro Ala
10??????????????????15??????????????????20CCA?AAG?TAT?CAA?GAT?GTT?TCT?TCC?GAA?AAG?CCG?AAA?GCC?CAA?AAA?GAC????????144Pro?Lys?Tyr?Gln?Asp?Val?Ser?Ser?Glu?Lys?Pro?Lys?Ala?Gln?Lys?Asp
25??????????????????30??????????????????35CAA?GGC?GGA?TAC?GGT?TTT?GCA?ATG?CGC?TTT?AAG?CGG?AGG?AAT?TGG?TAT????????192Gln?Gly?Gly?Tyr?Gly?Phe?Ala?Met?Arg?Phe?Lys?Arg?Arg?Asn?Trp?Tyr
40??????????????????45??????????????????50CAG?AAG?GCG?AAT?CCT?AAA?GAA?GAT?GAG?ATA?AAA?CTC?TCT?GAA?AAT?GAT????????240Gln?Lys?Ala?Asn?Pro?Lys?Glu?Asp?Glu?Ile?Lys?Leu?Ser?Glu?Asn?Asp?55??????????????????60??????????????????65??????????????????70TGG?GAA?CAA?ACG?GAT?AAT?GGT?GAT?ATC?AAA?AAC?CCT?TCC?AAA?CAA?AAA????????288Trp?Glu?Gln?Thr?Asp?Asn?Gly?Asp?Ile?Lys?Asn?Pro?Ser?Lys?Gln?Lys
75??????????????????80??????????????????85AAT?ATT?ATT?AAT?GCC?TTA?CCT?GGA?AAT?AAT?GGA?GGA?GCT?ACA?TTG?CAA????????336Asn?Ile?Ile?Asn?Ala?Leu?Pro?Gly?Asn?Asn?Gly?Gly?Ala?Thr?Leu?Gln
90??????????????????95?????????????????100GAT?TCC?AGT?CAA?GAA?AAT?CAG?GGT?ATA?TCT?AAG?GTT?ACG?GAC?TAT?CAC????????384Asp?Ser?Ser?Gln?Glu?Asn?Gln?Gly?Ile?Ser?Lys?Val?Thr?Asp?Tyr?His
105?????????????????110?????????????????115AAT?TTC?CAA?TAC?GTA?TGG?TCG?GGG?TTT?TTT?TAT?AAA?CAG?ATT?AAA?AAT????????432Asn?Phe?Gln?Tyr?Val?Trp?Ser?Gly?Phe?Phe?Tyr?Lys?Gln?Ile?Lys?Asn
120?????????????????125?????????????????130ACA?ATT?GAA?AAA?AAC?GGT?TCA?TCT?ATA?ACC?GCA?GCC?AGA?AAC?GGT?CCT????????480Thr?Ile?Glu?Lys?Asn?Gly?Ser?Ser?Ile?Thr?Ala?Ala?Arg?Asn?Gly?Pro135?????????????????140?????????????????145?????????????????150GAC?GGT?TAT?ATT?TTT?TAT?AAA?GGC?AAA?GAT?CCC?TCG?AGA?CAA?CTC?CCT????????528Asp?Gly?Tyr?Ile?Phe?Tyr?Lys?Gly?Lys?Asp?Pro?Ser?Arg?Gln?Leu?Pro
155?????????????????160?????????????????165GTA?TTG?GGA?CAG?GTT?ACG?TAT?AAA?GGG?ACT?TGG?GAT?TTC?TTA?ACT?GAT????????576Val?Leu?Gly?Gln?Val?Thr?Tyr?Lys?Gly?Thr?Trp?Asp?Phe?Leu?Thr?Asp
170?????????????????175?????????????????180GTG?AAA?ATA?AAT?CAG?AAA?TTT?ATA?GAT?TTA?GGG?AAT?ACT?TCT?ACG?AAA????????624Val?Lys?Ile?Asn?Gln?Lys?Phe?Ile?Asp?Leu?Gly?Asn?Thr?Ser?Thr?Lys
185?????????????????190?????????????????195CCC?GGC?GAC?CGA?TAT?AGT?GCT?TTT?TCC?GGG?GAG?TTG?GAT?TAT?ATC?GTC????????672Pro?Gly?Asp?Arg?Tyr?Ser?Ala?Phe?Ser?Gly?Glu?Leu?Asp?Tyr?Ile?Val
200?????????????????205?????????????????210AAT?AAA?GAT?AGC?GAT?AAG?AAA?GAC?GGG?CAC?GTA?GCA?AAG?GGA?TTA?ACA????????720Asn?Lys?Asp?Ser?Asp?Lys?Lys?Asp?Gly?His?Val?Ala?Lys?Gly?Leu?Thr215?????????????????220?????????????????225?????????????????230ACG?GAA?ATA?ACG?GTT?GAT?TTT?GAG?AAA?AAA?ACC?CTC?AAC?GGA?AAA?TTA????????768Thr?Glu?Ile?Thr?Val?Asp?Phe?Glu?Lys?Lys?Thr?Leu?Asn?Gly?Lys?Leu
235?????????????????240?????????????????245ATT?AAA?AAC?AAC?AGT?GTA?AGC?AAT?AAT?GAG?TTC?AAC?GCT?AAA?TAC?ACC????????816Ile?Lys?Asn?Asn?Ser?Val?Ser?Asn?Asn?Glu?Phe?Asn?Ala?Lys?Tyr?Thr
250?????????????????255?????????????????260ACC?CAA?TAC?TAT?AGC?CTT?GAT?GCG?ACG?CTT?AGG?GGA?AAC?CGC?TTC?AAC????????864Thr?Gln?Tyr?Tyr?Ser?Leu?Asp?Ala?Thr?Leu?Arg?Gly?Asn?Arg?Phe?Asn
265?????????????????270?????????????????275GGC?AAG?GCA?ACG?GCA?ACC?GAC?AAA?CCT?GGC?ACT?GGA?GAA?ACC?AAA?CAA????????912Gly?Lys?Ala?Thr?Ala?Thr?Asp?Lys?Pro?Gly?Thr?Gly?Glu?Thr?Lys?Gln
280?????????????????285?????????????????290CAT?CCC?TTT?GTT?TCC?GAC?TCG?TCT?TCT?TTG?AGC?GGC?GGC?TTT?TTC?GGC????????960His?Pro?Phe?Val?Ser?Asp?Ser?Ser?Ser?Leu?Ser?Gly?Gly?Phe?Phe?Gly295?????????????????300?????????????????305?????????????????310CCG?AAG?GGT?GAG?GAA?TTG?GGT?TTC?CGC?TTT?TTG?AGC?GAC?GAT?AAA?AAA???????1008Pro?Lys?Gly?Glu?Glu?Leu?Gly?Phe?Arg?Phe?Leu?Ser?Asp?Asp?Lys?Lys
315?????????????????320?????????????????325GTT?GCG?GTT?GTC?GGC?AGC?GCG?AAA?ACC?CAA?GAC?AAA?CCG?GGA?AAT?GGC???????1056Val?Ala?Val?Val?Gly?Ser?Ala?Lys?Thr?Gln?Asp?Lys?Pro?Gly?Asn?Gly
330?????????????????335?????????????????340GCG?GCG?GCT?TCA?GAC?GGC?GAG?GTG?CGG?CAG?CAT?CAA?ACG?GTG?CGG?CAG???????1104Ala?Ala?Ala?Ser?Asp?Gly?Glu?Val?Arg?Gln?His?Gln?Thr?Val?Arg?Gln
345?????????????????350?????????????????355CTA?GAT?GGC?TCT?GAA?AAC?GGT?AAG?CTG?ACC?ACG?GTT?TTG?GAT?GCG?GTC???????1152Leu?Asp?Gly?Ser?Glu?Asn?Gly?Lys?Leu?Thr?Thr?Val?Leu?Asp?Ala?Val
360?????????????????365?????????????????370GAG?CTG?ACG?CAC?GGC?GGC?ACA?GCA?ATC?AAA?AAT?CTC?GAC?AAC?TTC?AGC???????1200Glu?Leu?Thr?His?Gly?Gly?Thr?Ala?Ile?Lys?Asn?Leu?Asp?Asn?Phe?Ser375?????????????????380?????????????????385?????????????????390AAC?GCC?GCC?CAA?CTG?GTT?GTC?GAC?GGC?ATT?ATG?ATT?CCG?CTC?CCT?GCC???????1248Asn?Ala?Ala?Gln?Leu?Val?Val?Asp?Gly?Ile?Met?Ile?Pro?Leu?Pro?Ala
395?????????????????400?????????????????405GAG?GCT?TCC?GAA?AGT?GGG?AAC?AAT?CAA?GCC?AAT?CAA?GGT?ACA?AAT?GGC???????1296Glu?Ala?Ser?Glu?Ser?Gly?Asn?Asn?Gln?Ala?Asn?Gln?Gly?Thr?Asn?Gly
410?????????????????415?????????????????420GGA?ACA?GCC?TTT?ACC?CGC?AAA?TTT?GAC?CAC?ACG?CCG?AAA?AGC?GAT?GAA???????1344Gly?Thr?Ala?Phe?Thr?Arg?Lys?Phe?Asp?His?Thr?Pro?Lys?Ser?Asp?Glu
425?????????????????430?????????????????435AAA?GAC?ACC?CAA?GCA?GGT?ACG?GCG?GCG?AAT?GGC?AAT?CCA?GCC?GCT?TCA???????1392Lys?Asp?Thr?Gln?Ala?Gly?Thr?Ala?Ala?Asn?Gly?Asn?Pro?Ala?Ala?Ser
440?????????????????445?????????????????450AAT?ACG?GCA?GGT?GAT?ACC?AAT?GGC?AAA?ACA?AAA?ACC?TAT?GAA?GTC?GAA???????1440Asn?Thr?Ala?Gly?Asp?Thr?Asn?Gly?Lys?Thr?Lys?Thr?Tyr?Glu?Val?Glu455?????????????????460?????????????????465?????????????????470GTC?TGC?TGT?TCC?AAC?CTC?AAT?TAT?CTG?AAA?TAC?GGG?TTG?CTG?ACG?CGC???????1488Val?Cys?Cys?Ser?Asn?Leu?Asn?Tyr?Leu?Lys?Tyr?Gly?Leu?Leu?Thr?Arg
475?????????????????480?????????????????485AAA?ACT?GCC?GGT?AAC?ACG?GTG?GGA?AGC?GGC?AAC?GGC?AGC?CCA?ACC?GCC???????1536Lys?Thr?Ala?Gly?Asn?Thr?Val?Gly?Ser?Gly?Asn?Gly?Ser?Pro?Thr?Ala
490?????????????????495?????????????????500GCC?GCC?CAA?ACG?GAC?GCG?CAG?AGT?ATG?TTC?TTA?CAA?GGC?GAG?CGC?ACC???????1584Ala?Ala?Gln?Thr?Asp?Ala?Gln?Ser?Met?Phe?Leu?Gln?Gly?Glu?Arg?Thr
505?????????????????510?????????????????515GAT?GAA?AAA?GAG?ATT?CCA?AGC?GAG?CAA?AAC?GTC?GTT?TAT?CGG?GGG?TCT???????1632Asp?Glu?Lys?Glu?Ile?Pro?Ser?Glu?Gln?Asn?Val?Val?Tyr?Arg?Gly?Ser
520?????????????????525?????????????????530TGG?TAC?GGG?CAT?ATT?GCC?AAC?AGC?ACA?AGC?TGG?AGC?GGC?AAT?GCT?TCC???????1680Trp?Tyr?Gly?His?Ile?Ala?Asn?Ser?Thr?Ser?Trp?Ser?Gly?Asn?Ala?Ser535?????????????????540?????????????????545?????????????????550AAT?GCA?ACG?AGT?GGC?AAC?AAG?GCG?GAC?TTT?ACC?GTG?AAT?TTT?GGC?GAG???????1728Asn?Ala?Thr?Ser?Gly?Asn?Lys?Ala?Asp?Phe?Thr?Val?Asn?Phe?Gly?Glu
555?????????????????560?????????????????565AAA?AAA?ATT?ACC?GGC?ATG?TTA?ACC?GCT?GAA?AAC?AGG?CAG?GCG?GCA?ACC???????1776Lys?Lys?Ile?Thr?Gly?Met?Leu?Thr?Ala?Glu?Asn?Arg?Gln?Ala?Ala?Thr
570?????????????????575?????????????????580TTT?ACC?ATT?GAG?GGA?ACG?ATT?CAG?GGC?AAC?GGT?TTT?TCC?GGT?ACG?GCA???????1824Phe?Thr?Ile?Glu?Gly?Thr?Ile?Gln?Gly?Asn?Gly?Phe?Ser?Gly?Thr?Ala
585?????????????????590?????????????????595AAA?ACT?GCT?GAC?TCA?GGC?TTT?GAT?CTC?GAT?CAA?AGC?AAT?ACC?ACC?GGC???????1872Lys?Thr?Ala?Asp?Ser?Gly?Phe?Asp?Leu?Asp?Gln?Ser?Asn?Thr?Thr?Gly
600?????????????????605?????????????????610ACG?CCT?AAG?GCA?TAT?ATC?ACA?AAC?GCC?AAG?GTG?CAG?GGC?GGT?TTT?TAC???????1920Thr?Pro?Lys?Ala?Tyr?Ile?Thr?Asn?Ala?Lys?Val?Gln?Gly?Gly?Phe?Tyr615?????????????????620?????????????????625?????????????????630GGG?CCT?AAA?GCC?GAA?GAA?ATG?GGT?GGA?TGG?TTT?GCT?TAT?CCG?GGC?GAC???????1968Gly?Pro?Lys?Ala?Glu?Glu?Met?Gly?Gly?Trp?Phe?Ala?Tyr?Pro?Gly?Asp
635?????????????????640?????????????????645AGT?CAG?ACG?CAG?CGG?TCC?GCT?TCG?GGG?TCA?GGC?GCA?TCA?GCC?GCC?AAC???????2016Ser?Gln?Thr?Gln?Arg?Ser?Ala?Ser?Gly?Ser?Gly?Ala?Ser?Ala?Ala?Asn
650?????????????????655?????????????????660AGC?GCG?ACC?GTG?GTA?TTC?GGT?GCG?AAA?CGC?CAA?CAG?CTT?GTG?CAA???????????2061Ser?Ala?Thr?Val?Val?Phe?Gly?Ala?Lys?Arg?Gln?Gln?Leu?Val?Gln
665?????????????????670?????????????????675TAA???????????????????????????????????????????????????????????????????2064
(2) data of SEQIDNO:10:
(i) sequence signature:
(A) length: 687 amino acid
(B) type: amino acid
(D) topology structure: linearity
(ii) molecule type: protein
(ix) sequence description: SEQIDNO:10Met Val Leu Pro Val Phe Leu Ser Ser Ala Cys Leu Gly Gly Gly Gly-10-5 1 5Gly Ser Phe Asp Leu Asp Ser Val Asp Thr Glu Ala Pro Arg Pro Ala
10??????????????????15??????????????????20Pro?Lys?Tyr?Gln?Asp?Val?Ser?Ser?Glu?Lys?Pro?Lys?Ala?Gln?Lys?Asp
25??????????????????30??????????????????35Gln?Gly?Gly?Tyr?Gly?Phe?Ala?Met?Arg?Phe?Lys?Arg?Arg?Asn?Trp?Tyr
40??????????????????45??????????????????50Gln?Lys?Ala?Asn?Pro?Lys?Glu?Asp?Glu?Ile?Lys?Leu?Ser?Glu?Asn?Asp?55??????????????????60??????????????????65??????????????????70Trp?Glu?Gln?Thr?Asp?Asn?Gly?Asp?Ile?Lys?Asn?Pro?Ser?Lys?Gln?Lys
75??????????????????80??????????????????85Asn?Ile?Ile?Asn?Ala?Leu?Pro?Gly?Asn?Asn?Gly?Gly?Ala?Thr?Leu?Gln
90??????????????????95?????????????????100Asp?Ser?Ser?Gln?Glu?Asn?Gln?Gly?Ile?Ser?Lys?Val?Thr?Asp?Tyr?His
105?????????????????110?????????????????115Asn?Phe?Gln?Tyr?Val?Trp?Ser?Gly?Phe?Phe?Tyr?Lys?Gln?Ile?Lys?Asn
120?????????????????125?????????????????130Thr?Ile?Glu?Lys?Asn?Gly?Ser?Ser?Ile?Thr?Ala?Ala?Arg?Asn?Gly?Pro135?????????????????140?????????????????145?????????????????150Asp?Gly?Tyr?Ile?Phe?Tyr?Lys?Gly?Lys?Asp?Pro?Ser?Arg?Gln?Leu?Pro
155?????????????????160?????????????????165Val?Leu?Gly?Gln?Val?Thr?Tyr?Lys?Gly?Thr?Trp?Asp?Phe?Leu?Thr?Asp
170?????????????????175?????????????????180Val?Lys?Ile?Asn?Gln?Lys?Phe?Ile?Asp?Leu?Gly?Asn?Thr?Ser?Thr?Lys
185?????????????????190?????????????????195Pro?Gly?Asp?Arg?Tyr?Ser?Ala?Phe?Ser?Gly?Glu?Leu?Asp?Tyr?Ile?Val
200?????????????????205?????????????????210Asn?Lys?Asp?Ser?Asp?Lys?Lys?Asp?Gly?His?Val?Ala?Lys?Gly?Leu?Thr215?????????????????220?????????????????225?????????????????230Thr?Glu?Ile?Thr?Val?Asp?Phe?Glu?Lys?Lys?Thr?Leu?Asn?Gly?Lys?Leu
235?????????????????240?????????????????245Ile?Lys?Asn?Asn?Ser?Val?Ser?Asn?Asn?Glu?Phe?Asn?Ala?Lys?Tyr?Thr
250?????????????????255?????????????????260Thr?Gln?Tyr?Tyr?Ser?Leu?Asp?Ala?Thr?Leu?Arg?Gly?Asn?Arg?Phe?Asn
265?????????????????270?????????????????275Gly?Lys?Ala?Thr?Ala?Thr?Asp?Lys?Pro?Gly?Thr?Gly?Glu?Thr?Lys?Gln
280?????????????????285?????????????????290His?Pro?Phe?Val?Ser?Asp?Ser?Ser?Ser?Leu?Ser?Gly?Gly?Phe?Phe?Gly295?????????????????300?????????????????305?????????????????310Pro?Lys?Gly?Glu?Glu?Leu?Gly?Phe?Arg?Phe?Leu?Ser?Asp?Asp?Lys?Lys
315?????????????????320?????????????????325Val?Ala?Val?Val?Gly?Ser?Ala?Lys?Thr?Gln?Asp?Lys?Pro?Gly?Asn?Gly
330?????????????????335?????????????????340Ala?Ala?Ala?Ser?Asp?Gly?Glu?Val?Arg?Gln?His?Gln?Thr?Val?Arg?Gln
345?????????????????350?????????????????355Leu?Asp?Gly?Ser?Glu?Asn?Gly?Lys?Leu?Thr?Thr?Val?Leu?Asp?Ala?Val
360?????????????????365?????????????????370Glu?Leu?Thr?His?Gly?Gly?Thr?Ala?Ile?Lys?Asn?Leu?Asp?Asn?Phe?Ser375?????????????????380?????????????????385?????????????????390Asn?Ala?Ala?Gln?Leu?Val?Val?Asp?Gly?Ile?Met?Ile?Pro?Leu?Pro?Ala
395?????????????????400?????????????????405Glu?Ala?Ser?Glu?Ser?Gly?Asn?Asn?Gln?Ala?Asn?Gln?Gly?Thr?Asn?Gly
410?????????????????415?????????????????420Gly?Thr?Ala?Phe?Thr?Arg?Lys?Phe?Asp?His?Thr?Pro?Lys?Ser?Asp?Glu
425?????????????????430?????????????????435Lys?Asp?Thr?Gln?Ala?Gly?Thr?Ala?Ala?Asn?Gly?Asn?Pro?Ala?Ala?Ser
440?????????????????445?????????????????450Asn?Thr?Ala?Gly?Asp?Thr?Asn?Gly?Lys?Thr?Lys?Thr?Tyr?Glu?Val?Glu455?????????????????460?????????????????465?????????????????470Val?Cys?Cys?Ser?Asn?Leu?Asn?Tyr?Leu?Lys?Tyr?Gly?Leu?Leu?Thr?Arg
475?????????????????480?????????????????485Lys?Thr?Ala?Gly?Asn?Thr?Val?Gly?Ser?Gly?Asn?Gly?Ser?Pro?Thr?Ala
490?????????????????495?????????????????500Ala?Ala?Gln?Thr?Asp?Ala?Gln?Ser?Met?Phe?Leu?Gln?Gly?Glu?Arg?Thr
505?????????????????510?????????????????515Asp?Glu?Lys?Glu?Ile?Pro?Ser?Glu?Gln?Asn?Val?Val?Tyr?Arg?Gly?Ser
520?????????????????525?????????????????530Trp?Tyr?Gly?His?Ile?Ala?Asn?Ser?Thr?Ser?Trp?Ser?Gly?Asn?Ala?Ser535?????????????????540?????????????????545?????????????????550Asn?Ala?Thr?Ser?Gly?Asn?Lys?Ala?Asp?Phe?Thr?Val?Asn?Phe?Gly?Glu
555?????????????????560?????????????????565Lys?Lys?Ile?Thr?Gly?Met?Leu?Thr?Ala?Glu?Asn?Arg?Gln?Ala?Ala?Thr
570?????????????????575?????????????????580Phe?Thr?Ile?Glu?Gly?Thr?Ile?Gln?Gly?Asn?Gly?Phe?Ser?Gly?Thr?Ala
585?????????????????590?????????????????595Lys?Thr?Ala?Asp?Ser?Gly?Phe?Asp?Leu?Asp?Gln?Ser?Asn?Thr?Thr?Gly
600?????????????????605?????????????????610Thr?Pro?Lys?Ala?Tyr?Ile?Thr?Asn?Ala?Lys?Val?Gln?Gly?Gly?Phe?Tyr615?????????????????620?????????????????625?????????????????630Gly?Pro?Lys?Ala?Glu?Glu?Met?Gly?Gly?Trp?Phe?Ala?Tyr?Pro?Gly?Asp
635?????????????????640?????????????????645Ser?Gln?Thr?Gln?Arg?Ser?Ala?Ser?Gly?Ser?Gly?Ala?Ser?Ala?Ala?Asn
650?????????????????655?????????????????660Ser?Ala?Thr?Val?Val?Phe?Gly?Ala?Lys?Arg?Gln?Gln?Leu?Val?Gln
665?????????????????670?????????????????675
(2) data of SEQIDNO:11:
(i) sequence signature:
(A) length: 1808 base pairs
(B) type: Nucleotide
(C) chain: strand
(D) topology structure: linearity
(ii) molecule type: DNA (genome)
(vi) initial source:
(A) organism: meningitis naphthalene Se Shi coccus
(B) bacterial strain: IM2394
(ix) feature:
(A) title/key: sig-peptide
(B) position: 1..60
(ix) feature:
(A) title/key: mat-peptide
(B) position: 61..1797
(ix) feature:
(A) title/key: CDS
(B) position: 1..1797
(ix) feature:
(A) title/key: misc-feature
(B) position: 61..1035
(ix) feature:
(A) title/key: misc-feature
(B) position: 1036..1386
(ix) feature:
(A) title/key: misc-feature
(B) position: 1387..1797
(ix) feature:
(A) title/key: misc-combination
(B) position: 46..1050
(xi) sequence description: SEQIDNO:11ATG AAC AAT CCA TTG GTA AAT CAG GCT GCT ATG GTG CTG CCT GTG TTT 48Met Asn Asn Pro Leu Val Asn Gln Ala Ala Met Val Leu Pro Val Phe-20-15-10-5TTG TTG AGT GCT TGT CTG GGT GGC GGC GGC AGT TTC GAT TTG GAC AGC 96Leu Leu Ser Ala Cys Leu Gly Gly Gly Gly Ser Phe Asp Leu Asp Ser
1???????????????????5??????????????10GTG?GAA?ACC?GTG?CAA?GAT?ATG?CAC?TCC?AAA?CCT?AAG?TAT?GAG?GAT?GAA????????144Val?Glu?Thr?Val?Gln?Asp?Met?His?Ser?Lys?Pro?Lys?Tyr?Glu?Asp?Glu
15??????????????????20??????????????????25AAA?AGC?CAG?CCT?GAA?AGC?CAA?CAG?GAT?GTA?TCG?GAA?AAC?AGC?GGC?GCG????????192Lys?Ser?Gln?Pro?Glu?Ser?Gln?Gln?Asp?Val?Ser?Glu?Asn?Ser?Gly?Ala
30??????????????????35??????????????????40GCT?TAT?GGC?TTT?GCA?GTA?AAA?CTA?CCT?CGC?CGG?AAT?GCA?CAT?TTT?AAT????????240Ala?Tyr?Gly?Phe?Ala?Val?Lys?Leu?Pro?Arg?Arg?Asn?Ala?His?Phe?Asn?45??????????????????50??????????????????55??????????????????60CCT?AAA?TAT?AAG?GAA?AAG?CAC?AAA?CCA?TTG?GGT?TCA?ATG?GAT?TGG?AAA????????288Pro?Lys?Tyr?Lys?Glu?Lys?His?Lys?Pro?Leu?Gly?Ser?Met?Asp?Trp?Lys
65??????????????????70??????????????????75AAA?CTG?CAA?AGA?GGA?GAA?CCA?AAT?AGT?TTT?AGT?GAG?AGG?GAT?GAA?TTG????????336Lys?Leu?Gln?Arg?Gly?Glu?Pro?Asn?Ser?Phe?Ser?Glu?Arg?Asp?Glu?Leu
80??????????????????85??????????????????90GAA?AAA?AAA?CGG?GGT?AGT?TCT?GAA?CTT?ATT?GAA?TCA?AAA?TGG?GAA?GAT????????384Glu?Lys?Lys?Arg?Gly?Ser?Ser?Glu?Leu?Ile?Glu?Ser?Lys?Trp?Glu?Asp
95?????????????????100?????????????????105GGG?CAA?AGT?CGT?GTA?GTT?GGT?TAT?ACA?AAT?TTC?ACT?TAT?GTC?CGT?TCG????????432Gly?Gln?Ser?Arg?Val?Val?Gly?Tyr?Thr?Asn?Phe?Thr?Tyr?Val?Arg?Ser
110?????????????????115?????????????????120GGA?TAT?GTT?TAC?CTT?AAT?AAA?AAT?AAT?ATT?GAT?ATT?AAG?AAT?AAT?ATA????????480Gly?Tyr?Val?Tyr?Leu?Asn?Lys?Asn?Asn?Ile?Asp?Ile?Lys?Asn?Asn?Ile125?????????????????130?????????????????135?????????????????140GTT?CTT?TTT?GGA?CCT?GAC?GGA?TAT?CTT?TAC?TAT?AAA?GGG?AAA?GAA?CCT????????528Val?Leu?Phe?Gly?Pro?Asp?Gly?Tyr?Leu?Tyr?Tyr?Lys?Gly?Lys?Glu?Pro
145?????????????????150?????????????????155TCC?AAG?GAG?CTG?CCA?TCG?GAA?AAG?ATA?ACT?TAT?AAA?GGT?ACT?TGG?GAT????????576Ser?Lys?Glu?Leu?Pro?Ser?Glu?Lys?Ile?Thr?Tyr?Lys?Gly?Thr?Trp?Asp
160?????????????????165?????????????????170TAT?GTT?ACT?GAT?GCT?ATG?GAA?AAA?CAA?AGG?TTT?GAA?GGA?TTG?GGT?AGT????????624Tyr?Val?Thr?Asp?Ala?Met?Glu?Lys?Gln?Arg?Phe?Glu?Gly?Leu?Gly?Ser
175?????????????????180?????????????????185GCA?GCA?GGA?GGA?GAT?AAA?TCG?GGG?GCG?TTG?TCT?GCA?TTA?GAA?GAA?GGG????????672Ala?Ala?Gly?Gly?Asp?Lys?Ser?Gly?Ala?Leu?Ser?Ala?Leu?Glu?Glu?Gly
190?????????????????195?????????????????200GTA?TTG?CGT?AAT?CAG?GCA?GAG?GCA?TCA?TCC?GGT?CAT?ACC?GAT?TTT?GGT????????720Val?Leu?Arg?Asn?Gln?Ala?Glu?Ala?Ser?Ser?Gly?His?Thr?Asp?Phe?Gly205?????????????????210?????????????????215?????????????????220ATG?ACT?AGT?GAG?TTT?GAG?GTT?GAT?TTT?TCT?GAT?AAA?ACA?ATA?AAG?GGC????????768Met?Thr?Ser?Glu?Phe?Glu?Val?Asp?Phe?Ser?Asp?Lys?Thr?Ile?Lys?Gly
225?????????????????230?????????????????235ACA?CTT?TAT?CGT?AAC?AAC?CGT?ATT?ACT?CAA?AAT?AAT?AGT?GAA?AAC?AAA????????816Thr?Leu?Tyr?Arg?Asn?Asn?Arg?Ile?Thr?Gln?Asn?Asn?Ser?Glu?Asn?Lys
240?????????????????245?????????????????250CAA?ATA?AAA?ACT?ACG?CGT?TAC?ACC?ATT?CAA?GCA?ACT?CTT?CAC?GGC?AAC????????864Gln?Ile?Lys?Thr?Thr?Arg?Tyr?Thr?Ile?Gln?Ala?Thr?Leu?His?Gly?Asn
255?????????????????260?????????????????265CGT?TTC?AAA?GGT?AAG?GCG?TTG?GCG?GCA?GAT?AAA?GGT?GCA?ACA?AAT?GGA????????912Arg?Phe?Lys?Gly?Lys?Ala?Leu?Ala?Ala?Asp?Lys?Gly?Ala?Thr?Asn?Gly
270?????????????????275?????????????????280AGT?CAT?CCC?TTT?ATT?TCC?GAC?TCC?GAC?AGT?TTG?GAA?GGC?GGA?TTT?TAC????????960Ser?His?Pro?Phe?Ile?Ser?Asp?Ser?Asp?Ser?Leu?Glu?Gly?Gly?Phe?Tyr285?????????????????290?????????????????295?????????????????300GGG?CCG?AAA?GGC?GAG?GAA?CTT?GCC?GGT?AAA?TTC?TTG?AGC?AAC?GAC?AAC????????1008Gly?Pro?Lys?Gly?Glu?Glu?Leu?Ala?Gly?Lys?Phe?Leu?Ser?Asn?Asp?Asn
305?????????????????310?????????????????315AAA?GTT?GCA?GCG?GTG?TTT?GGT?GCG?AAG?CAG?AAA?GAT?AAG?AAG?GAT?GGG????????1056Lys?Val?Ala?Ala?Val?Phe?Gly?Ala?Lys?Gln?Lys?Asp?Lys?Lys?Asp?Gly
320?????????????????325?????????????????330GAA?AAC?GCG?GCA?GGG?CCT?GCA?ACG?GAA?ACC?GTG?ATA?GAT?GCA?TAC?CGT????????1104Glu?Asn?Ala?Ala?Gly?Pro?Ala?Thr?Glu?Thr?Val?Ile?Asp?Ala?Tyr?Arg
335?????????????????340?????????????????345ATT?ACC?GGC?GAG?GAG?TTT?AAG?AAA?GAG?CAA?ATA?GAC?AGT?TTT?GGA?GAT????????1152Ile?Thr?Gly?Glu?Glu?Phe?Lys?Lys?Glu?Gln?Ile?Asp?Ser?Phe?Gly?Asp
350?????????????????355?????????????????360GTG?AAA?AAG?CTG?CTG?GTT?GAC?GGA?GTG?GAG?CTT?TCA?CTG?CTG?CCG?TCT????????1200Val?Lys?Lys?Leu?Leu?Val?Asp?Gly?Val?Glu?Leu?Ser?Leu?Leu?Pro?Ser365?????????????????370?????????????????375?????????????????380GAG?GGC?AAT?AAG?GCG?GCA?TTT?CAG?CAC?GAG?ATT?GAG?CAA?AAC?GGC?GTG???????1248Glu?Gly?Asn?Lys?Ala?Ala?Phe?Gln?His?Glu?Ile?Glu?Gln?Asn?Gly?Val
385?????????????????390?????????????????395AAG?GCA?ACG?GTG?TGT?TGT?TCC?AAC?TTG?GAT?TAC?ATG?AGT?TTT?GGG?AAG???????1296Lys?Ala?Thr?Val?Cys?Cys?Ser?Asn?Leu?Asp?Tyr?Met?Ser?Phe?Gly?Lys
400?????????????????405?????????????????410CTG?TCA?AAA?GAA?AAT?AAA?GAC?GAT?ATG?TTC?CTG?CAA?GGT?GTC?CGC?ACT???????1344Leu?Ser?Lys?Glu?Asn?Lys?Asp?Asp?Met?Phe?Leu?Gln?Gly?Val?Arg?Thr
415?????????????????420?????????????????425CCA?GTA?TCC?GAT?GTG?GCG?GCA?AGG?ACG?GAG?GCA?AAC?GCC?AAA?TAT?CGC???????1392Pro?Val?Ser?Asp?Val?Ala?Ala?Arg?Thr?Glu?Ala?Asn?Ala?Lys?Tyr?Arg
430?????????????????435?????????????????440GGT?ACT?TGG?TAC?GGA?TAT?ATT?GCC?AAC?GGC?ACA?AGC?TGG?AGC?GGC?GAA???????1440Gly?Thr?Trp?Tyr?Gly?Tyr?Ile?Ala?Asn?Gly?Thr?Ser?Trp?Ser?Gly?Glu445?????????????????450?????????????????455?????????????????460GCC?TCC?AAT?CAG?GAA?GGT?GGT?AAT?AGG?GCA?GAG?TTT?GAC?GTG?GAT?TTT???????1488Ala?Ser?Asn?Gln?Glu?Gly?Gly?Asn?Arg?Ala?Glu?Phe?Asp?Val?Asp?Phe
465?????????????????470?????????????????475TCC?ACT?AAA?AAA?ATC?AGT?GGC?ACA?CTG?ACG?GCA?AAA?GAC?CGT?ACG?TCT???????1536Ser?Thr?Lys?Lys?Ile?Ser?Gly?Thr?Leu?Thr?Ala?Lys?Asp?Arg?Thr?Ser
480?????????????????485?????????????????490CCT?GCG?TTT?ACT?ATT?ACT?GCC?ATG?ATT?AAG?GAC?AAC?GGT?TTT?TCA?GGT???????1584Pro?Ala?Phe?Thr?Ile?Thr?Ala?Met?Ile?Lys?Asp?Asn?Gly?Phe?Ser?Gly
495?????????????????500?????????????????505GTG?GCG?AAA?ACC?GGT?GAA?AAC?GGC?TTT?GCG?CTG?GAT?CCG?CAA?AAT?ACC???????1632Val?Ala?Lys?Thr?Gly?Glu?Asn?Gly?Phe?Ala?Leu?Asp?Pro?Gln?Asn?Thr
510?????????????????515?????????????????520GGA?AAT?TCC?CAC?TAT?ACG?CAT?ATT?GAA?GCC?ACT?GTA?TCC?GGC?GGT?TTC???????1680Gly?Asn?Ser?His?Tyr?Thr?His?Ile?Glu?Ala?Thr?Val?Ser?Gly?Gly?Phe525?????????????????530?????????????????535?????????????????540TAC?GGC?AAA?AAC?GCC?ATC?GAG?ATG?GGC?GGA?TCG?TTC?TCA?TTT?CCG?GGA???????1728Tyr?Gly?Lys?Asn?Ala?Ile?Glu?Met?Gly?Gly?Ser?Phe?Ser?Phe?Pro?Gly
545?????????????????550?????????????????555AAT?GCA?CCA?GAG?GGA?AAA?CAA?GAA?AAA?GCA?TCG?GTG?GTA?TTC?GGT?GCG???????1776Asn?Ala?Pro?Glu?Gly?Lys?Gln?Glu?Lys?Ala?Ser?Val?Val?Phe?Gly?Ala
560?????????????????565?????????????????570AAA?CGC?CAA?CAG?CTT?GTG?CAA?TAAGCACGGC?T??????????????????????????????1808Lys?Arg?Gln?Gln?Leu?Val?Gln
575, (2) data of SEQIDNO:12:, (i) sequence signature:, (A) length: 599 amino acid, (B) type: amino acid, (D) topology structure: linearity, (ii) molecule type: protein, (ix) sequence description: SEQIDNO:12Met Asn Asn Pro Leu Val Asn Gln Ala Ala Met Val Leu Pro Val Phe-20-15-10-5Leu Leu Ser Ala Cys Leu Gly Gly Gly Gly Ser Phe Asp Leu Asp Ser
1???????????????5??????????????????10Val?Glu?Thr?Val?Gln?Asp?Met?His?Ser?Lys?Pro?Lys?Tyr?Glu?Asp?Glu
15??????????????????20??????????????????25Lys?Ser?Gln?Pro?Glu?Ser?Gln?Gln?Asp?Val?Ser?Glu?Asn?Ser?Gly?Ala
30??????????????????35??????????????????40Ala?Tyr?Gly?Phe?Ala?Val?Lys?Leu?Pro?Arg?Arg?Asn?Ala?His?Phe?Asn?45??????????????????50??????????????????55??????????????????60Pro?Lys?Tyr?Lys?Glu?Lys?His?Lys?Pro?Leu?Gly?Ser?Met?Asp?Trp?Lys
65??????????????????70??????????????????75Lys?Leu?Gln?Arg?Gly?Glu?Pro?Asn?Ser?Phe?Ser?Glu?Arg?Asp?Glu?Leu
80??????????????????85??????????????????90Glu?Lys?Lys?Arg?Gly?Ser?Ser?Glu?Leu?Ile?Glu?Ser?Lys?Trp?Glu?Asp
95?????????????????100?????????????????105Gly?Gln?Ser?Arg?Val?Val?Gly?Tyr?Thr?Asn?Phe?Thr?Tyr?Val?Arg?Ser
110?????????????????115?????????????????120Gly?Tyr?Val?Tyr?Leu?Asn?Lys?Asn?Asn?Ile?Asp?Ile?Lys?Asn?Asn?Ile?125????????????????130?????????????????135?????????????????140Val?Leu?Phe?Gly?Pro?Asp?Gly?Tyr?Leu?Tyr?Tyr?Lys?Gly?Lys?Glu?Pro
145?????????????????150?????????????????155Ser?Lys?Glu?Leu?Pro?Ser?Glu?Lys?Ile?Thr?Tyr?Lys?Gly?Thr?Trp?Asp
160?????????????????165?????????????????170Tyr?Val?Thr?Asp?Ala?Met?Glu?Lys?Gln?Arg?Phe?Glu?Gly?Leu?Gly?Ser
175?????????????????180?????????????????185Ala?Ala?Gly?Gly?Asp?Lys?Ser?Gly?Ala?Leu?Ser?Ala?Leu?Glu?Glu?Gly
190?????????????????195?????????????????200Val?Leu?Arg?Asn?Gln?Ala?Glu?Ala?Ser?Ser?Gly?His?Thr?Asp?Phe?Gly205?????????????????210?????????????????215?????????????????220Met?Thr?Ser?Glu?Phe?Glu?Val?Asp?Phe?Ser?Asp?Lys?Thr?Ile?Lys?Gly
225?????????????????230?????????????????235Thr?Leu?Tyr?Arg?Asn?Asn?Arg?Ile?Thr?Gln?Asn?Asn?Ser?Glu?Asn?Lys
240?????????????????245?????????????????250Gln?Ile?Lys?Thr?Thr?Arg?Tyr?Thr?Ile?Gln?Ala?Thr?Leu?His?Gly?Asn
255?????????????????260?????????????????265Arg?Phe?Lys?Gly?Lys?Ala?Leu?Ala?Ala?Asp?Lys?Gly?Ala?Thr?Asn?Gly
270?????????????????275?????????????????280Ser?His?Pro?Phe?Ile?Ser?Asp?Ser?Asp?Ser?Leu?Glu?Gly?Gly?Phe?Tyr285?????????????????290?????????????????295?????????????????300Gly?Pro?Lys?Gly?Glu?Glu?Leu?Ala?Gly?Lys?Phe?Leu?Ser?Asn?Asp?Asn
305?????????????????310?????????????????315Lys?Val?Ala?Ala?Val?Phe?Gly?Ala?Lys?Gln?Lys?Asp?Lys?Lys?Asp?Gly
320?????????????????325?????????????????330Glu?Asn?Ala?Ala?Gly?Pro?Ala?Thr?Glu?Thr?Val?Ile?Asp?Ala?Tyr?Arg
335??????????????????340?????????????????345Ile?Thr?Gly?Glu?Glu?Phe?Lys?Lys?Glu?Gln?Ile?Asp?Ser?Phe?Gly?Asp
350?????????????????355?????????????????360Val?Lys?Lys?Leu?Leu?Val?Asp?Gly?Val?Glu?Leu?Ser?Leu?Leu?Pro?Ser365?????????????????370?????????????????375?????????????????380Glu?Gly?Asn?Lys?Ala?Ala?Phe?Gln?His?Glu?Ile?Glu?Gln?Asn?Gly?Val
385?????????????????390?????????????????395Lys?Ala?Thr?Val?Cys?Cys?Ser?Asn?Leu?Asp?Tyr?Met?Ser?Phe?Gly?Lys
400?????????????????405?????????????????410Leu?Ser?Lys?Glu?Asn?Lys?Asp?Asp?Met?Phe?Leu?Gln?Gly?Val?Arg?Thr
415?????????????????420?????????????????425Pro?Val?Ser?Asp?Val?Ala?Ala?Arg?Thr?Glu?Ala?Asn?Ala?Lys?Tyr?Arg
430?????????????????435?????????????????440Gly?Thr?Trp?Tyr?Gly?Tyr?Ile?Ala?Asn?Gly?Thr?Ser?Trp?Ser?Gly?Glu445?????????????????450?????????????????455?????????????????460Ala?Ser?Asn?Gln?Glu?Gly?Gly?Asn?Arg?Ala?Glu?Phe?Asp?Val?Asp?Phe
465?????????????????470?????????????????475Ser?Thr?Lys?Lys?Ile?Ser?Gly?Thr?Leu?Thr?Ala?Lys?Asp?Arg?Thr?Ser
480?????????????????485?????????????????490Pro?Ala?Phe?Thr?Ile?Thr?Ala?Met?Ile?Lys?Asp?Asn?Gly?Phe?Ser?Gly
495?????????????????500?????????????????505Val?Ala?Lys?Thr?Gly?Glu?Asn?Gly?Phe?Ala?Leu?Asp?Pro?Gln?Asn?Thr
510?????????????????515?????????????????520Gly?Asn?Ser?His?Tyr?Thr?His?Ile?Glu?Ala?Thr?Val?Ser?Gly?Gly?Phe525?????????????????530?????????????????535?????????????????540Tyr?Gly?Lys?Asn?Ala?Ile?Glu?Met?Gly?Gly?Ser?Phe?Ser?Phe?Pro?Gly
545?????????????????550?????????????????555Asn?Ala?Pro?Glu?Gly?Lys?Gln?Glu?Lys?Ala?Ser?Val?Val?Phe?Gly?Ala
560????????????????565????????????????570Lys?Arg?Gln?Gln?Leu?Val?Gln
575
(2) data of SEQIDNO:13:
(i) sequence signature:
(A) length: 19 base pairs
(B) type: Nucleotide
(C) chain: strand
(D) topology structure: linearity
(ii) molecule type: DNA (genome)
(xi) sequence description: SEQIDNO:13TGCTATGGTG CTGCCTGTG
2) data of SEQIDNO:14:
(i) sequence signature:
(A) length: 19 base pairs
(B) type: Nucleotide
(C) chain: strand
(D) topology structure: linearity
(ii) molecule type: DNA (genome)
(xi) sequence description: SEQIDNO:14:TGCCGTCGAA GCCTTATTC
(2) data of SEQIDNO:15:
(i) sequence signature:
(A) length: 25 base pairs
(B) type: Nucleotide
(C) chain: strand
(D) topology structure: linearity
(ii) molecule type: DNA (genome)
(xi) sequence description: SEQIDNO:15:AAGACCAAGG CGGATACGGT TTTGC
(2) data of SEQIDNO:16:
(i) sequence signature:
(A) length: 26 base pairs
(B) type: Nucleotide
(C) chain: strand
(D) topology structure: linearity
(ii) molecule type: DNA (genome)
(xi) sequence description: SEQIDNO:16:GAAGACGAGT CGGAAACAAA GGGATG
Claims (19)
1. pharmaceutical composition, it comprises that (i) has the subunit (TbpB) of lower molecular weight of human transferrin acceptor (HTR) of meningitis naphthalene Se Shi coccus bacterial strain of the dna sequence dna of coding TbpB, or the (ii) fragment of described TbpB, wherein the dna sequence dna (a) in (i) contains 2 AvaII restriction sites, 3 HincII restriction sites, without any the VspI restriction site and without any the XhoI restriction site or, (b) primer P4 of being 5 '-GAAGACGAGTCGGAAACAAAGGGATG-3 ' by means of primer P3 and the general formula of general formula 5 '-AAGACCAAGGCGGATACGGTTTTGC-3 ' preferably, can produce 765 to 775 Nucleotide, the preferably polynucleotide of 772 Nucleotide (bacterial strain of BZ83 cohort) from this sequence by PCR (polymerase chain reaction).
2. pharmaceutical composition according to claim 1, wherein TbpB obtains from the meningitis naphthalene Se Shi coccus strain as the part of ET-5 complex body or pedigree III.
3. pharmaceutical composition according to claim 1 and 2, wherein TbpB is that meningitis naphthalene Se Shi coccus bacterial strain from dna sequence dna with coding TbpB obtains, described dna sequence dna shows by 1184,477 and the AvaII restriction map formed of 3 fragments of 415nt, and by 1155,385,276 and the HincII restriction map (bacterial strain of BZ83 cohort) formed of 4 fragments of 257nt.
4. pharmaceutical composition according to claim 3, wherein TbpB has as the described aminoacid sequence of SEQIDNO:2 (bacterial strain BZ83).
5. according to each described pharmaceutical composition of claim 1-4, it comprise in addition (i) from meningitis naphthalene Se Shi coccus obtain as the part of ET-5 complex body and have first other TbpB of the dna sequence dna of coding TbpB, or the fragment of (ii) described first other TbpB, wherein the dna sequence dna (a) in (i) does not contain AvaII and XhoI restriction site, perhaps, (b) primer P4 of being 5 '-GAAGACGAGTCGGAAACAAAGGGATG-3 ' by means of primer P3 and the general formula of general formula 5 '-AAGACCAAGGCGGATACGGTTTTGC-3 ' preferably, can produce 840 to 850 Nucleotide, the preferably polynucleotide of 844 Nucleotide (bacterial strain of M982 cohort) from this sequence by PCR.
6. pharmaceutical composition according to claim 5, wherein first other TbpB is that meningitis naphthalene Se Shi coccus bacterial strain from dna sequence dna with coding TbpB obtains, and described dna sequence dna contains 1 VspI restriction site and 3 HincII restriction sites (bacterial strain of M982 cohort).
7. pharmaceutical composition according to claim 6, wherein TbpB is that meningitis naphthalene Se Shi coccus bacterial strain from dna sequence dna with coding TbpB obtains, described dna sequence dna shows by 1311 and the VspI restriction map formed of 2 fragments of 769nt and by 1129,319,281 and the HincII restriction map (bacterial strain of M982 cohort) formed of 4 fragments of 259nt.
8. according to each described pharmaceutical composition of claim 1-7, it comprise in addition (i) from meningitis naphthalene Se Shi coccus obtain as the part of ET-5 complex body and have second other TbpB of the dna sequence dna of coding TbpB, or the fragment of (ii) described second other TbpB, wherein the dna sequence dna (a) in (i) contains 1 AvaII restriction site and 2 VspI restriction sites, 1 XhoI restriction site and 2 HincII restriction sites or, (b) primer P4 of being 5 '-GAAGACGAGTCGGAAACAAAGGGATG-3 ' by means of primer P3 and the general formula of general formula 5 '-AAGACCAAGGCGGATACGGTTTTGC-3 ' preferably, can produce 800 to 810 Nucleotide, the preferably polynucleotide of 805 Nucleotide (bacterial strains of 8680 cohorts) from this sequence by PCR.
9. pharmaceutical composition according to claim 8, wherein second other TbpB is that meningitis naphthalene Se Shi coccus bacterial strain from dna sequence dna with coding TbpB obtains, described dna sequence dna shows by 1507 and the AvaII restriction map formed of 2 fragments of 445nt, by 1298,470 and the VspI restriction map formed of 3 fragments of 266nt and by 1551 and the XhoI restriction map formed of 2 fragments of 483nt, with by 1191,527 and the HincII restriction map (bacterial strains of 8680 cohorts) formed of 3 fragments of 316nt.
10. pharmaceutical composition according to claim 9, wherein second other TbpB has the aminoacid sequence (bacterial strain 8680) that is shown in SEQIDNO:6.
11. according to each described pharmaceutical composition of claim 1-10, it comprises that in addition the homology degree that (i) has a sequence that itself and SEQIDNO:4 show is at least 85%, preferably the TbpB of the aminoacid sequence of at least 90% (M982 type); Or the (ii) fragment of described TbpB.
12. pharmaceutical composition according to claim 11, wherein TbpB has the aminoacid sequence (M982 bacterial strain) that is shown in SEQIDNO:4.
13. according to each described pharmaceutical composition of claim 1-12, it comprises that in addition homology degree that (i) has a sequence that itself and SEQIDNO:8 show is at least the TbpB of the aminoacid sequence of 95% (bacterial strain of B16B6 type); Or the (ii) fragment of described TbpB.
14. according to each described pharmaceutical composition of claim 1-13, wherein will be as the TbpB of each definition of claim 1-4, first other TbpB as each definition of claim 5-7, second other TbpB as each definition of claim 8-10, TbpB as claim 11 or 12 definition, or combine with corresponding high molecular subunit (Tbp1) as the TbpB of claim 13 definition, so that formation HTR.
15. pharmaceutical composition comprises the dna molecular of coding as the TbpB of each definition of claim 1-4.
16. pharmaceutical composition according to claim 15, it comprises coding first other dna molecular as the TbpB of each definition of claim 5-7 in addition.
17. according to claim 15 or 16 described pharmaceutical compositions, it comprises second the other dna molecular of coding as the TbpB of each definition of claim 8-10.
18. according to each described pharmaceutical composition of claim 15-17, it comprises the dna molecular of coding as the TbpB of claim 11 or 12 definition in addition.
19. according to each described pharmaceutical composition of claim 15-18, it comprises the dna molecular of coding as the TbpB of claim 13 definition in addition.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9710301A FR2767060B1 (en) | 1997-08-07 | 1997-08-07 | MENINGOCOCCAL VACCINE WITH BZ83 STRAIN VALENCE |
| FR97/10301 | 1997-08-07 | ||
| PCT/FR1998/001730 WO1999007741A1 (en) | 1997-08-07 | 1998-08-03 | Meningococcus vaccine comprising the valence of bz83 strain |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1241193A true CN1241193A (en) | 2000-01-12 |
Family
ID=9510254
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN98801479A Pending CN1241193A (en) | 1997-08-07 | 1998-08-03 | Meningococcus vaccine comprising valence of BZ23 strain |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP0948534A1 (en) |
| JP (1) | JP2001503068A (en) |
| CN (1) | CN1241193A (en) |
| AU (1) | AU8987598A (en) |
| CA (1) | CA2267066A1 (en) |
| FR (1) | FR2767060B1 (en) |
| HU (1) | HUP0001451A3 (en) |
| NO (1) | NO991558D0 (en) |
| NZ (1) | NZ334992A (en) |
| WO (1) | WO1999007741A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105980562A (en) * | 2013-12-02 | 2016-09-28 | A·B·施里维斯 | Immunogenic compositions and vaccines derived from bacterial surface receptor proteins |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0107219D0 (en) * | 2001-03-22 | 2001-05-16 | Microbiological Res Authority | Immunogenic commensal neisseria sequences |
| EP3229835A1 (en) * | 2014-12-09 | 2017-10-18 | Sanofi Pasteur | Compositions comprising n. meningitidis proteins |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5292869A (en) * | 1989-04-27 | 1994-03-08 | The Board Of Governors Of The University | Method for isolating and purifying transferrin and lactoferrin receptor proteins from bacteria and the preparation of vaccines containing the same |
| FR2682041B1 (en) * | 1991-10-03 | 1994-01-14 | Pasteur Merieux Serums Vaccins | VACCINE AGAINST NEISSERIA MENINGITIDIS INFECTIONS. |
| FR2692592B1 (en) * | 1992-06-19 | 1995-03-31 | Pasteur Merieux Serums Vacc | DNA fragments encoding the Neisseria meningitidis transferrin receptor subunits and methods of expressing them. |
| FR2720408B1 (en) * | 1994-05-31 | 1996-08-14 | Pasteur Merieux Serums Vacc | Fragments Tbp2 of Neisseria meningitidis. |
| FR2739624B1 (en) * | 1995-10-10 | 1997-12-05 | Pasteur Merieux Serums Vacc | NEW NEISSERIA MENINGITIDIS TBP2 SUBUNIT |
-
1997
- 1997-08-07 FR FR9710301A patent/FR2767060B1/en not_active Expired - Fee Related
-
1998
- 1998-08-03 AU AU89875/98A patent/AU8987598A/en not_active Abandoned
- 1998-08-03 NZ NZ334992A patent/NZ334992A/en unknown
- 1998-08-03 JP JP11511756A patent/JP2001503068A/en active Pending
- 1998-08-03 CN CN98801479A patent/CN1241193A/en active Pending
- 1998-08-03 WO PCT/FR1998/001730 patent/WO1999007741A1/en not_active Application Discontinuation
- 1998-08-03 EP EP98941530A patent/EP0948534A1/en not_active Withdrawn
- 1998-08-03 CA CA002267066A patent/CA2267066A1/en not_active Abandoned
- 1998-08-03 HU HU0001451A patent/HUP0001451A3/en unknown
-
1999
- 1999-03-30 NO NO991558A patent/NO991558D0/en not_active Application Discontinuation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105980562A (en) * | 2013-12-02 | 2016-09-28 | A·B·施里维斯 | Immunogenic compositions and vaccines derived from bacterial surface receptor proteins |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0948534A1 (en) | 1999-10-13 |
| FR2767060A1 (en) | 1999-02-12 |
| HUP0001451A2 (en) | 2001-04-28 |
| CA2267066A1 (en) | 1999-02-18 |
| HUP0001451A3 (en) | 2001-09-28 |
| AU8987598A (en) | 1999-03-01 |
| FR2767060B1 (en) | 2000-02-11 |
| NO991558L (en) | 1999-03-30 |
| JP2001503068A (en) | 2001-03-06 |
| NZ334992A (en) | 2001-09-28 |
| WO1999007741A1 (en) | 1999-02-18 |
| NO991558D0 (en) | 1999-03-30 |
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