CN101115502A - Vaccines against neisseria meningitidis - Google Patents

Abstract

Various polypeptides, or a variant or fragment thereof or a fusion of these are described which are useful in a vaccine. The polypeptide may be a polypeptide comprising the amino acid sequence selected from any one of SEQ ID Nos (2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68); or a fragment or variant thereof or a fusion of such fragment or variant, and is useful in a vaccine against Neisseira meningitidis.

Description

The vaccine of anti-Neisseria meningitidis

The present invention relates to vaccine and uses thereof, especially for the vaccine of meningococcal disease (meningococcaldisease).

Enumerating or discussing and should not be interpreted as and admit that this document is a part or the known general knowledge of prior art the file formerly delivered in this description.Take in file cited in description as a reference at this.

Infected by microbes is the serious threat to human and animal's health always, particularly at many pathogenic microbes, particularly antibacterial, for antimicrobial such as antibiosis have resistance or the situation of the resistance that can become under all the more so.

Vaccination provides and has resisted the alternative method of infected by microbes, but usually is difficult to identify the immunogen that is applicable to vaccine, and they should be safe and effective to the multiple different isolates of pathogenic microbes (particularly hereditary various microorganism).Though might develop microorganism with intact (intact) basically as immunogenic vaccine, such as the attenuated live bacterium that in the gene of decision virulence, comprises a place or many places sudden change usually, but be not that all microorganisms all are applicable to the method, and be not the concrete microorganism of always wishing the method is used for always guaranteeing safety.Also have, some microbial expression can be simulated the molecule of host protein, and these molecules are undesired in the vaccine.

To developing the important concrete microorganism of a class of further vaccine is Neisseria meningitidis (Neisseria meningitidis), it causes meningococcal disease, this is a kind of life-threatening infection, although introduced link coupled (conjugate) serogroup C polysaccharide vaccine, this infection in Europe, North America, developing country and other place remain the major reason sero-group of death of child.This is because the infection that is caused by serogroup B strain (NmB) is still popular, the polysialic acids pod membrane that this bacterial strain express alpha 2-8 connects.(serogroup) refer to the polysaccharide pod membrane of on this antibacterial, expressing about the term " sero-group " of Neisseria meningitidis.The common sero-group that causes disease in Britain is B, and is A in Africa.The meningococcus septicemia is kept high case fatality rate always; And survivor is usually left over great psychology and/or physical disability.Behind nonspecific antecedent disease, the meningococcus septicemia can be rendered as the explosive disease that corresponding antimicrobial therapy and all ancillary methods (full supportive measures) are difficult to cure.Therefore, the best method of the public health threat of resistance meningococcal disease is preventative vaccination.

The non-specific early stage clinical sign of meningococcal infection and explosive process mean that treatment usually is invalid.Therefore, think vaccination be the available strategy that alleviates the global disease burden that pathogen thus causes (Feavers (2000) ABC of meningococcal diversity.Nature 404,451-2).Be used to prevent the existing vaccine of Neisseria meningitidis serogroups A, C, W135 and Y infection based on the polysaccharide pod membrane (Anderson et al (1994) Safety andimmunogenicity of meningococcal A and C polysaccharide conjugate vaccine inadults.Infect Immun.62, the 3391-33955 that are positioned on the bacterium surface; Leach et al (1997) Induction ofimmunologic memory in Gambian children by vaccination in infancy with agroup A plus group C meningococcal polysaccharide-protein conjugate vaccine.JInfect Dis.175,200-4; Lieberman et al (1996) Safety and immunogenicity of aserogroups A/C Neisseria meningitidis oligosaccharide-protein conjugate vaccinein young children.A randomized controlled trial.J.American Med.Assoc.275,1499-1503).The progress of leading to the vaccine that antiserum group B infects is more difficult, because its pod membrane, i.e. the sialic homopolymer of α 2-8 connection are relatively poor relatively immunogen in human body.This be because it be shared in the epi-position that people's cell adhesion molecule N-CAM1 go up to express (Finne et al (1983) Antigenicsimilarities between brain components and bacteria causing meningitis.Implications for vaccine development and pathogenesis.Lancet 2,355-357).In fact, in fact the immunne response of generation antiserum group B pod membrane may prove deleterious.Given this, still need to be used to prevent the novel vaccine of Neisseria meningitidis serogroup B infection.

The related mensuration of the most reliable (validated) immunology of the protective effect of meningococcemia disease (correlate) is serum sterilizing algoscopy (SBA).Antibody (often being the IgG2a subclass) mediation complement deposits, assembles the ability of membrane attack complex and cracking antibacterial in the SBA assessment serum on the bacterial cell surface.In SBA, with the serial dilution of datum purpose bacterial exposure in serum with appointment complement source.Measure the number of survival antibacterial, SBA is defined as the dilution inverse of mediation 50% highest serum that kills and wounds.The protective effect that the measurable antiserum group of SBA C infects, it is widely used as the synonym (surrogate) of the immunity of anti-NmB infection.Importantly, in the assessment, SBA is the ready-made mark of immunity before vaccine clinical, and it provides the suitable terminal point of clinical trial.

The great majority of NmB vaccine development make great efforts to be devoted to determine effective protein protomer.Among " oppositely vaccinology " (Reverse vaccinology) significant investment is arranged, it is sought in genome sequence might be the albumen of heterologous antigen at surface expression, and tests them produce significant ability of replying in animal.Yet the method is subjected to following restriction: 1) be used to predict the antigenic computerized algorithm of surface expression, 2) fail to express many potential immunogens and 3) to the complete dependency of Mus immunne response.

The key of successful vaccine is, determines at extensive multiple disease separated strain rather than is limited to concrete sero-group or clone's group (clonal group) can both cause the antigen sero-group of protective effect.(we are called immunogenic genetic screening (Genetic Screening for Immunogens) or GSI) are used to be separated in conservative antigen between the various microbial strains of heredity the genetic screening method, for example, in the meningococcus bacterial strain, isolated such antigen with this method.Its way is to use the GSI Identifying micro-organisms antigen that hereinafter describes in detail such as I (Neisseria meningitidis) antigens; And the function of the immunne response that is caused by recombinant antigen by assessment and the antigenic protection of assessment are renderd a service and are verified (referring to embodiment with referring to PCT/GB2004/005441 (on July 7th, 2005 is open as WO 2005/060995), in this income as a reference).In essence, the GSI method relates to the method for Identifying micro-organisms polypeptide, and this polypeptide is relevant with the immunne response in the animal that meets with this microorganism, and this method comprises the steps: that (1) provides the multiple different mutants of this microorganism; (2) described multiple microbial mutation body is contacted with the antibody of the animal that produces anti-this microorganism or its a part of immunne response, under the condition of described contact,, then kill this microbial mutation body in case described antibody combines with described microbial mutation body; (3) select the microbial mutation body of surviving in the step (2); (4) identify the gene that comprises described sudden change in the microbial mutation body of any survival; (5) evaluation is by the polypeptide of this gene code.Will be appreciated that according to the mode of identifying that these polypeptide adopted, is highly appropriate with these polypeptide as antigenic polypeptide.

As described more in detail among the embodiment, the concrete gene of identifying by the GSI method is the NBM0341 (TspA) of Neisseria meningitidis, NMB0338, NMB 1345, NMB0738, NBM0792 (NadC family), NMB0279, NMB2050, NMB1335 (CreA), NMB2035, NMB1351 (Fmu and Fmv), NMB1574 (IIvC), NMB1298 (rsuA), NMB1856 (LysR family), NMB0119, NMB1705 (rfak), NMB2065 (HemK), NMB0339, NMB0401 (putA), NMB1467 (PPX), NMB2056, NMB0808, NMB0774 (upp), NMA0078, NMB0337 (branched-chain amino acid transferring enzyme), NMB0191 (ParA family), NMB1710 (glutamte dehydrogenase (gdhA), NMB0062 (rfbA-1), NMB 1583 (HisB), NMB0377, NMB0264, NMB1333, NMB1036, NMB1176, NMB1359 and NMB1138 gene.The genome sequence of Neisseria meningitidis can be from for example The Institute of Genome Research (TIGR); Www.tigr.org obtains.

Although these genes constitute a genomic part that has checked order, just known to the inventor, they do not separate as yet, are not made (and not separating as yet) as yet and be there is no indication that their encoded polypeptide can be used as the composition of vaccine by their encoded polypeptides.

Therefore, the present invention includes above and the isolating gene described in the embodiment, and variant and fragment, and this type of variant and segmental fusions, also comprise said gene encoded polypeptides and variant thereof and fragment, and the fusions of this type of fragment and variant.Hereinafter more detailed description variant, fragment and fusions.Preferably, the variant of the gene that above provides, fragment and fusions are those of coded polypeptide, and described polypeptide can produce the neutralizing antibody of anti-Neisseria meningitidis.Similarly, preferably, for the those polypeptides that has above provided sequence, their variant, fragment and fusions are those of neutralizing antibody that produce anti-Neisseria meningitidis.Neutralizing antibody can generate in immune any animal is arranged, for example rat, mice or rabbit.The present invention also comprises isolating polynucleotide, has provided those polypeptides or coding variant, fragment or the fusions of sequence (coding region of preferable separate) among its coding embodiment.The present invention also comprises the expression vector that comprises these type of polynucleotide and comprises the host cell (seeing for details hereinafter) of these type of polynucleotide and carrier.Polypeptide described in the embodiment is to identify the antigen that obtains by the inventive method.

The molecular biology method that is used to implement the inventive method is well-known in the art, for example from Sambrook ﹠amp; Russell (2001) Molecular Cloning, a laboratory manual, the third edition, Cold Spring Harbor laboratory Press, Cold Spring Harbor, New York, in this income as a reference.

The variant of gene can reach the clone, separate or synthesize this gene and prepare by for example identifying related gene in other microorganism or in other strain of this microorganism.Be typically, the variant of gene is to have at least 70% sequence homogeneity with the gene that above provides, more preferably at least 85% sequence homogeneity, most preferably those of at least 95% sequence homogeneity.Certainly, tolerable substitutes, deletes and inserts.Similarity degree between a kind of nucleotide sequence and the another kind can use the GAP program of University of Wisconsin ComputerGroup to measure.

The variant of gene also refers under stringent condition with this gene those of hybridization to take place.So-called " strictness " is meant that gene is fixed on the film, and probe (being length＞200 nucleotide in this example) in solution, makes gene and probe hybridization, and the probe of fixed gene/hybridization cleaned 10 minutes in 65 ℃ in 0.1 * SSC.SSC refers to 0.15M sodium chloride/0.015M sodium citrate.

The fragment that can prepare gene (or mutant gene) for example is 20%, 30%, 40%, 50%, 60%, 70%, 80% or 90% of a complete genome.Preferred fragment comprises entire coded sequence or part coded sequence.Variant and fragment can merge with other irrelevant polynucleotide.

Polynucleotide encoding has immunogenic polypeptide, the antibody response of the animal of described polypeptide and the described microorganism of experience, and described microorganism is the microorganism that identifies this gene.

Antigen can be that the sequence of this polypeptide can be derived easily from this gene order by institute's genes identified encoded polypeptides above.In other embodiments, antigen can be the fragment of the polypeptide identified, perhaps can be the variant polypeptides of being identified, perhaps can be the fusions of described polypeptide or fragment or variant.

Therefore, a concrete aspect of the present invention provides to comprise and has been selected from SEQ ID No 2,4,6,8,10,12,14,16,18,20,22,24,26,28,30,32,34,36,38,40,42,44,46, the polypeptide of arbitrary aminoacid sequence in 48,50,52,54,56,58,60,62,64,66,68; Or the fusions of its fragment or variant or this type of fragment or variant.Therefore, the invention provides following isolating albumen, or its fragment or variant, or these fusions: NMB0341 as mentioned below, NMB1583, NMB1345, NMB0738, NMB0792, NMB0279, NMB2050, NMB1335, NMB2035, NMB1351, NMB1574, NMB1298, NMB1856, NMB0119, NMB1705, NMB2065, NMB0339, NMB0401, NMB1467, NMB2056, NMB0808, NMB0774, NMA0078, NMB0337, NMB0191, NMB1710, NMB0062, NMB1333, NMB0377, NMB0264, NMB1036, NMB1176, NMB1359 and NMB1138.

The fragment that can prepare the polypeptide of being identified for example is 20%, 30%, 40%, 50%, 60%, 70%, 80% or 90% of a complete polypeptide.Typically, described fragment is at least 10,15,20,30,40,50,100 or amino acids more, but is less than 500,400,300 or 200 aminoacid.Can prepare variant polypeptides." variant " comprises conservative or nonconservative insertion, deletion and substitute, and wherein this type of changes and does not change described proteic normal function basically." conservative substituting " refers to such as Gly Ala; Val, Ile, Leu; Asp, Glu; Asn, Gln; Ser, Thr; Lys, Arg; And Phe, the Tyr combination.This type of variant can use well-known protein engineering and site-directed mutagenesis method to prepare.

The variant that one class is concrete is by those of above-mentioned mutant gene coding, for example from those of related microorganisms or this other strain of microorganism.Typically, described variation polypeptide has at least 70% sequence homogeneity with the polypeptide that uses the inventive method to identify, more preferably at least 85% sequence homogeneity, most preferably at least 95% sequence homogeneity.

Percentage ratio sequence homogeneity between two peptide species can use suitable computer program to measure, the GAP program of University of Wisconsin Genetic Computing Group for example should be understanded percentage ratio homogeneity and calculate after the best comparison in that peptide sequence is carried out.

(Thompson et al, (1994) Nucleic Acids Res 22 4673-80) compares perhaps can to use Clustal W program.Used parameter can be as follows:

Compare parameter fast in pairs: K-tuple (tuple) (speech (word)) long (size); 1, window long (window size); 5, breach point penalty (gap penalty); 3, top diagonal number (number of top diagonals); 5.Methods of marking (Scoring method): x percentage ratio.

Multiple ratio is to parameter: breach is opened point penalty (gap open penalty); 10, breach extends point penalty (gapextension penalty); 0.05.Rating matrix (Scoring matrix): BLOSUM.

Fusions can be the fusions that merges with any suitable polypeptide.Typically, described polypeptide is can strengthen those of the immunne response of the polypeptide that merges with it.Merging the spouse can be the polypeptide of being convenient to purification, for example can be convenient to those of purification at the binding site of fixed part (moiety) in the affinity column for example by formation.Therefore, merge that the spouse can comprise few histidine or in conjunction with other aminoacid of cobalt or nickel ion.It can also be the epi-position of monoclonal antibody, such as the Myc epi-position.

Just as discussed above, variation polypeptide or polypeptide fragment or these fusions are typically those of the neutralizing antibody that produces anti-Neisseria meningitidis.

Thus, the present invention also comprises the antigenic as mentioned above method of preparation, and maybe can pass through the antigen that this method obtains by what this method obtained.

Can polynucleotide of the present invention be cloned in the carriers such as expression vector as known in the art.Examples of such carriers is found in host cell, such as antibacterial, yeast, mammal and insect host cell.Antigen of the present invention can easily be expressed by polynucleotide in proper host cell, and therefrom separates, for using in the vaccine.

Typical expression system comprises commercial pET expression vector series and e. coli host cell, such as BL21.Polypeptide expressed can be come purification by any method that this area is known.Be antigen to be merged with the fusion spouse who combines affinity column as mentioned above, and use this affinity column (for example nickel or cobalt affinity column) this fusions of purification easily.

The polynucleotide (such as dna molecular) that should understand antigen or coding for antigens are particularly suitable for being used for vaccine.In the sort of situation, antigen is purification (perhaps synthesize by peptide prepare in the antigenic situation purifying antigen from these synthetic any pollutant) from generate this antigenic host cell.Be typically, be less than 5%, preferably be less than after 2%, 1%, 0.5%, 0.1%, 0.01%, antigen is formulated in the vaccine at the pollutant that antigen contained.Antigen preferably is substantially free of pyrogen.Therefore, the present invention also comprises and contains antigenic vaccine, and prepares the method for vaccine, comprises suitable carriers such as antigen and phosphate-buffered saline are made up.Antigen of the present invention can be used separately, but preferably it is made into medicinal proportional preparation with one or more acceptable carriers.Carrier must be " acceptable ", and this is meant that carrier should be compatible with antigen of the present invention and harmless to the receptor of this carrier.Be typically, carrier is aseptic and does not contain the water or the saline of pyrogen.

Vaccine also can comprise adjuvant.Preferably the patient is carried out active immunity inoculation (activeimmunisation).In the method, one or more antigens are made the immunogenicity preparaton that contains suitable adjuvant and carrier, and be applied to the patient in a known way.Suitable adjuvant comprises the complete or Freund of Fu Shi, muramyldipeptide, " Iscoms " of EP 109942, EP 180564 and EP 231039, aluminium hydroxide, saponin, DEAE-glucosan, neutral oil (such as miglyol), vegetable oil (such as Oleum Arachidis hypogaeae semen), liposome, Pluronic polyhydric alcohol or Ribi adjuvant system (referring to for example GB-A-2 189141)." Pluronic " is registered trade mark.The patient who treats immunity is the patient who needs the protection of acquisition anti-microbial infection.

The present invention also comprises Pharmaceutical composition, and it comprises polypeptide of the present invention or its variant or fragment or these fusions or polynucleotide of the present invention or its variant or fragment or these fusions and pharmaceutically acceptable carrier as discussed above.

Aforementioned antigen of the present invention (or these type of antigenic polynucleotide of encoding) or its preparaton can be used by any conventional method, comprise oral and parenteral (for example subcutaneous or intramuscular) injection.Treatment can be made up of single agent or the multi-agent that continues for some time.

Vaccine of the present invention be should understand,, human medicine and veterinary drug field can be used for according to its antigenic component (or polynucleotide).

The disease that is caused by microorganism is known in many animals such as domestic animal.Vaccine of the present invention when containing the polynucleotide of suitable antigen or coding for antigens, can be used for the people, but also can be used for for example cattle, sheep, pig, horse, dog and cat, and is used for poultry such as chicken, turkey, duck and goose.

Therefore, the present invention also comprise to individual vaccination with the opposing method of microorganism, this method comprises to individuality uses aforesaid antigen (or polynucleotide of coding for antigens) or vaccine.The present invention also comprises the purposes of aforesaid antigen (or polynucleotide of coding for antigens) in the vaccine that preparation is inoculated to individuality.

Antigen of the present invention can be as the unique antigen in the vaccine, perhaps it can with other the antigen combined use at identical or different disease microorganism.About Neisseria meningitidis, resulting antigen to responding property of NmB can with employed composition associating in the vaccine of anti-A and/or C sero-group.It can also provide the antigenicity composition associating of protection easily with resisting haemophilus (Haemophilus) and/or streptococcus pneumoniae (Streptococcus pneumoniae).Other antigenicity composition can be a polypeptide, and perhaps they can be other antigenicity compositions, such as polysaccharide.Polysaccharide also can be used for enhance immunity and replys (referring to for example Makela et al (2002) Expert Rev.Vaccines 1,399-410).

Above particularly preferably be in vaccine and the method for vaccination, antigen is by above polypeptide or above-mentioned variant or the fragment or the fusions (or the described antigenic polynucleotide of encoding) of (in embodiment) described any gene code, and the disease that needs vaccination to put up a resistance is that Neisseria meningitidis infects (meningococcal disease).

Below will be by the more detailed description the present invention of following non-limiting example.

Embodiment 1: in the Neisseria meningitidis to immunogenic genetic screening (GSI)

GSI application in this embodiment comprises that in the insertion mutant library of Neisseria meningitidis, screening is to the more insensitive bacterial strain of the lethal effect of bactericidal properties antibody.GSI sees PCT/GB2005/005441 (on July 7th, 2005 is open as WO 2005/060995) for details.

In the mutant library of the separated strain MC58 that checks order of NmB, screen by mice serum with the negative same strain of anti-pod membrane (a capsule minus ofthe same strain), we have proved the effectiveness of GSI.40,000 mutants use the serum that produces through homologous strain intraperitoneal immune mouse to analyze altogether; The SBA of the anti-wild-type strain of this serum is about 2,000.When the library being exposed to the serum (it kills all wild-type bacteriums) of dilution in 1: 560, detect the mutant of survival.In order to determine that the transposon insertion in the survival mutant is exactly the reason of resisting the ability of lethal effect, these sudden changes are backcrossed (backcross) in parent plant, and confirmed that the reverse mutation strain more has resistance than wild type to lethal effect in SBA.Separate transposon insertion site by marker rescue (marker rescue), check the sequence that is subjected to the gene that this transposon influences with this.We have found wherein two kinds of affected gene: TspA and NMB0338.TspA is the surface antigen that causes strong CD4+T cell response, can be discerned by the patients serum (Kizil et al (1999) Infect Immun.67,3533-41).The function of NMB0338 gene is unknown before this, and its coding be it is predicted the polypeptide that contains two membrane spaning domains and be positioned at cell surface.By the NMB0338 amino acid sequence coded be:

MERNGVFGKIVGNRILRMSSEHAAASYPKPCKSFKLAQSWFRVRSCLGGVFIYGA

NMKLIYTVIKIIILLLFLLLAVINTDAVTFSYLPGQKFDLPLIVVLFGAFVVGII

FGMFALFGRLLSLRGENGRLRAEVKKNARLTGKELTAPPAQNAPESTKQP

Except the requirement of publilc health, NmB is used for GSI several practical advantages: a) this antibacterial can carry out heredity tracking (tractable); B) kill and wound and directly to measure what this antibacterial was caused by the effector immunologic mechanism; C) can obtain three kinds of genome sequences (being respectively the IV-A of serogroups A, the ET-5 of serogroup B 5 and the ET-37 of serogroup C) with separated strain of different sero-groups and clone's pedigree; And d) there is the clinical resource of detailed sign can supply this work used.

GSI has two potential restrictions.The first, the target thing of bactericidal properties antibody may be absolutely necessary.But this is unlikely, because all known target things of bactericidal properties antibody are not absolutely necessary among the NmB, and the requisite gene outcome of none targeting of the bacterial vaccine of current permission.The second, contain anti-multiple antigenic antibody in the serum, lose the survival that single a kind of antigen may not influence mutant.We prove for a long time, even in the process that the serum with anti-homologous strain screens, use suitable dilution serum still to identify related antigen.

The major advantage of GSI is: 1) the high flux step does not relate to and too requires flow process (such as protein expression/purification and immunity inoculation) technology or expensive; With 2) but end user's sample in the test but not only depends on animal data.GSI can find out in the surface protein those albumen that cause bactericidal activity rapidly, thus the less relatively material standed for of labor more.

1. Use GSI to identify the target thing of bactericidal properties antibody

Use Mus serum and end user's serum of anti-allos bacterial strain to identify cross-reactive antigen.Described serum derives from:

I) with the allos bacterial strain through general approach mice immunized: the selection of described bacterial strain and/or make up makes the separated strain of avoiding having identical immunologic pattern (immunotype) and inferior sero-group (sub-serotype);

The patient's of the known separated strain of Neisseria meningitidis acute stage and convalescent serum (the Dr R.Wall by Northwick Park provides) have ii) been infected;

Appointment adventitia bubble (outer membrane vesicle, OMV) before the volunteer's of vaccine the immunity and the immunity back sample (providing by MeningococcalReference Laboratory) of NmB separated strain H44/76 iii) are provided.

These serum sources all have concrete merits and demerits.

A) in GSI, use serum through the animal of allos bacterial strain (serogroups A that has promptly checked order or C bacterial strain) immunity, MC58 mutant library is screened.We prove, have caused the cross reactivity bactericidal properties antibody response of antiserum group A and C bacterial strain with attenuated live NmB immunity inoculation.By the marker rescue of ruined gene, identified non-existent antigen in the enhanced mutant of when human serum is arranged, surviving.

B) identified the sudden change of giving at the resistance of allos serum lethal effect, and determined this gene outcome whether also be the serogroups A that checked order and C bacterial strain (being respectively Z2491 and FAM18) kill and wound the target thing.Homologue at these genes of genomic data library lookup.When having homologue, insert from MC58 mutant amplification transposon, and it is transformed importing serogroups A and C bacterial strain.The relatively mutant of each sero-group and the relative survival of wild-type strain.Therefore, GSI can provide the information of whether guarding and whether can reach (accessible) about the target thing of bactericidal activity in the different strains of any sero-group of Neisseria meningitidis, immunologic pattern and inferior sero-group fast.

C) use convalescent or accept the people's of allos OMV vaccine (derived from H44/76) serum, test can be resisted mice serum and be survived enhanced mutant.This solves whether the target thing can cause bactericidal properties antibody in human body major issue.In other vaccine method, this information can only expend a lot of financial resources in the late period of clinical trial and obtain later on after require to produce vaccine candidate object according to GMP.

Advantage is, the high throughput analysis that GSI is to use existing simple technique to carry out.In human body, cause bactericidal properties antibody and mediate the antigen that kills and wounds a plurality of bacterial strains and can be identified rapidly, because GSI is being flexibly aspect use bacterial isolates and the serum.Analyze the mutant that end user's serum is selected in the mode identical with the mutant that uses Mus serum to select.

2. The antigenic antibody response of assessment reorganization GSI

The commodity in use carrier, at expression in escherichia coli albumen and vaccine, described albumen is as the target thing of bactericidal properties antibody and be resumed phase patient's serum identification.From the MC58 corresponding open reading-frame that increases, and be connected to carrier by PCR, under the control of T7 or arabinose inducible promoter, express respectively to allow albumen such as among pCR Topo CT or the pBAD/His.Be purified into above-mentioned recombiant protein from total protein of cell, this process is by carrying out with the terminal His label that merges of described PROTEIN C on nickel or cobalt post.

New Zealand white rabbit subcutaneous injection 25 μ g purifying protein and the incomplete Freunds of growing up, twice totally immunity inoculation is around its interbody spacer.Before immunity inoculation,, check existing anti-Nm antibody in the animal serum by full cell ELISA.Animal with initial serum titer＜1: 2 carries out the immunity inoculation experiment.Obtain serum after the immunity inoculation after two weeks of immunity inoculation for the second time.In order to confirm that specific antibody produces, and passes through i) ELISA that analyzes and ii) use the cell of wild type and corresponding mutant (producing) to carry out at the proteic Western of purification by GSI, before the test immunity and immunity back serum.

At MC58 (homologous strain), and the serogroups A and the C bacterial strain that have checked order, carry out SBA with the rabbit immune serum.Test carries out twice at least, and is each triplicate.SBA＞8 are considered as significantly.The gained result provides the albumen material standed for whether can cause the evidence of bactericidal properties antibody as recombiant protein.

3. Determine the antigenic protection effect of GSI

Test all material standed fors live ability of germ attack of opposing that watches for animals, because this can assess the immunity (cellular immunity or humoral immunity) of either side in single test.We have set up the active immunity and the protection model of anti-bacterial infection alive.In this model, adult mice is accepted the germ attack of living the 0th day and immunity in the 21st day at the 28th day intraperitoneal, is 10 in the dextran iron (property ferrum source as a supplement) ⁶Or 10 ⁷CFU MC58.This model class be similar to the protection effect of assessment Tbps immunity model (Danveet al (1993) Vaccine 11,1214-1220).Bacteremia takes place in infection in back 4 hours in nonimmune animal, demonstrates the sign of systemic disease during by 24 hours.We can prove the protection effect that the two meningococcemia viable bacteria of attenuation Nm bacterial strain and proteantigen is attacked for a long time; PorA is the outer membrane protein that causes bactericidal properties antibody, but its antigenicity change is very big, therefore be not first-selected vaccine candidate object (Bart etal (1999) Infect Immun.67,3832-3846).

Six week BALB/c mouse in age (every group of 35 animals) are subcutaneous acceptance 25 μ g recombiant protein and incomplete Freunds at the 0th and 21 day, accept 10 at the 28th day intraperitoneal then ⁶(15 animals) or 10 ⁷(15 animals) CFU MC58 attacks.Use two kinds of challenge doses to check the effect of vaccine at high and low challenge dose; Obtain serum the 28th day five animal remaining from every group and five animals before first time immunity inoculation, and be stored in-70 ℃ of further immunological testings of confession.Animals of control group is accepted: i) independent adjuvant; The folding again PorA that ii) recombinates; Or iii) Nm attenuated live bacterial strain.In order to reduce the sum of animal in the matched group, once test a plurality of groups (number of group=5 material standed for+3 contrasts) that five material standed fors are arranged.The survival condition that compares each treated animal by Mann Whitney U check.When every group of 15 mices/agent, these experiments demonstrate the difference of surviving between 25% group.

For the vaccine that demonstrates remarkable protective effect at attack, carry out repeated experiments to confirm this discovery.In addition, also cause the bacteremic protective effect of opposing, measure bacteremic level in the experimentation in the second time in order to determine the vaccination of using material standed for to carry out; Back 22 hours of infection blood sample collection in immunity and nonimmune animal (the bacteremia level is the highest at this moment).Use two tail (two-tailed) Student-T check analysis results, to determine whether bacteremia significantly alleviates in vaccinated animal.

Employed other material and method

The mutation of Neisseria meningitidis

For research, make up mutant by in vitro mutagenesis to Neisseria meningitidis.With the Tn5 derivant genomic DNA of Neisseria meningitidis is carried out mutation, described Tn5 derivant contains encodes the mark of kalamycin resistance and the origin of replication of function is arranged in escherichia coli.These elements are by compound (composite) terminal gang of Tn5.Carry out the swivel base reaction with the high activity variant of Tn5, and with T4 archaeal dna polymerase and ligase DNA plerosis under the condition that ATP and multiple nucleotide are arranged.DNA with this reparation changes into the kalamycin resistance bacterium with Neisseria meningitidis.Southern analyzes confirmation, and each mutant only comprises the single insertion of described transposon.

The serum sterilizing algoscopy (Serum bactericidal assay, SBA)

Antibacterial is gone up overnight incubation at solid medium (brain-heart infusion medium (brain heartinfusion media) that contains the Levanthals fill-in), in experiment line once more on solid medium in the morning on the same day, cultivated 4 hours then.After this, antibacterial is collected in the phosphate buffered saline (PBS) and counting.SBA at the 1ml volume, contain complement source (young rabbit or people) and about 10 ⁵Carry out under the condition of individual colony-forming units.When incubation finishes, collect antibacterial, and be applied on the solid medium to reclaim the antibacterial that survives.

Separate transposon insertion site

Reclaim genomic DNA by standard method from interested mutant, and digested 3 hours, come purification by the phenol extracting then with PvuII, EcoRV and DraI.Then DNA is spent the night in 16 ℃ of oneself's connections under the situation that the T4 dna ligase is arranged with 100 microlitre volumes, precipitation is used for by electroporation escherichia coli being changed into the kalamycin resistance bacterium then.

Embodiment 2: other screening and result thereof

GSI has been used to screen the library that about 40,000 MC58 insert mutant.This library is to use the transposon that contains the pACYC184 origin of replication, makes up by external Tn5 mutation.

Selecting MC58 is because it is the serogroup B separated strain of Neisseria meningitidis, and the complete genome group sequence of this bacterial strain is known.

Always come this library of parllel screening in contrast, and shown from the clump count of this library and wild type recovery with wild-type strain.

The selection of using Mus serum to carry out

At first, use is through the serum analysis library of the animal of YH102 attenuated strain immunity.Three intraperitoneal of adult mice (Balb/C) accept 10 ⁸Individual colony-forming units, and collect serum behind 10 days of immunity inoculation the last time.

This Screening and Identification obtains enhanced several mutants of resistance that serum is killed and wounded.As following this is confirmed: separate each mutant, in initial genetic background, rebuild described sudden change, and test of the susceptibility of each mutant once more, and compare with wild type to the splitting action of complement-mediated.Transposon inserts and is arranged in following gene:

NMB0341 (TspA) DNA sequence

ATGCCCGCCGGCCGACTGCCCCGCCGATGCCCGATGATGACGAAATTTACAGACTGTACG

CGGTCAAACCGTATTCAGCCGCCAACCCACAGGGGATACATCTTGAAAAACAACAGACAA

ATCAAACTGATTGCCGCCTCCGTCGCAGTTGCCGCATCCTTTCAGGCACATGCTGGACTG

GGCGGACTGAATATCCAGTCCAACCTTGACGAACCCTTTTCCGGCAGCATTACCGTAACC

GGCGAAGAAGCCAAAGCCCTGCTAGGCGGCGGCAGCGTTACCGTTTCCGAAAAAGGCCTG

ACCGCCAAAGTCCACAAGTTGGGCGACAAAGCCGTCATTGCCGTTTCTTCCGAACAGGCA

GTCCGCGATCCCGTCCTGGTGTTCCGCATCGGCGCAGGCGCACAGGTACGCGAATACACC

GCCATCCTCGATCCTGTCGGCTACTCGCCCAAAACCAAATCTGCACTTTCAGACGGCAAG

ACACACCGCAAAACCGCTCCGACAGCAGAGTCCCAAGAAAATCAAAACGCCAAAGCCCTC

CGCAAAACCGATAAAAAAGACAGCGCGAACGCAGCCGTCAAACCGGCATACAACGGCAAA

ACCCATACCGTCCGCAAAGGCGAAACGGTCAAACAGATTGCCGCCGCCATCCGCCCGAAA

CACCTGACGCTCGAACAGGTTGCCGATGCGCTGCTGAAGGCAAACCCAAATGTTTCCGCA

CACGGCAGACTGCGTGCGGGCAGCGTGCTTCACATTCCGAATCTGAACAGGATCAAAGCG

GAACAACCCAAACCGCAAACGGCGAAACCCAAAGCCGAAACCGCATCCATGCCGTCCGAA

CCGTCCAAACAGGCAACGGTAGAGAAACCGGTTGAAAAACCTGAAGCAAAAGTTGCCGCG

CCCGAAGCAAAAGCGGAAAAACCGGCCGTTCGACCCGAACCTGTACCCGCTGCAAATACT

GCCGCATCGGAAACCGCTGCCGAATCCGCCCCCCAAGAAGCCGCCGCTTCTGCCATCGAC

ACGCCGACCGACGAAACCGGTAACGCCGTTTCCGAACCTGTCGAACAGGTTTCTGCCGAA

GAAGAAACCGAAAGCGGACTGTTTGACGGTCTGTTCGGCGGTTCGTACACCTTGCTGCTT

GCCGGCGGAGGCGCGGCATTAATCGCCCTGCTGCTGCTTTTGCGCCTTGCCCAATCCAAA

CGCGCGCGCCGTACCGAAGAATCCGTCCCTGAGGAAGAGCCTGACCTTGACGACGCGGCA

GACGACGGCATAGAAATCACCTTTGCCGAAGTCGAAACTCCGGCAACGCCCGAACCCGCT

CCGAAAAACGATGTAAACGACACACTTGCCTTAGATGGGGAATCTGAAGAAGAGTTATCG

GCAAAACAAACGTTCGATGTCGAAACCGATACGCCTTCCAACCGCATCGACTTGGATTTC

GACAGCCTGGCAGCCGCGCAAAACGGCATTTTATCCGGCGCACTTACGCAGGATGAAGAA

ACCCAAAAACGCGCGGATGCCGATTGGAACGCCATCGAATCCACAGACAGCGTGTACGAG

CCCGAGACCTTCAACCCGTACAACCCTGTCGAAATCGTCATCGACACGCCCGAACCGGAA

TCTGTCGCCCAAACTGCCGAAAACAAACCGGAAACCGTCGATACCGATTTCTCCGACAAC

CTGCCCTCAAACAACCATATCGGCACAGAAGAAACAGCTTCCGCAAAACCTGCCTCACCC

TCCGGACTGGCAGGCTTCCTGAAGGCTTCCTCGCCCGAAACCATCTTGGAAAAAACAGTT

GCCGAAGTCCAAACACCGGAAGAGTTGCACGATTTCCTGAAAGTGTACGAAACCGATGCC

GTCGCGGAAACTGCGCCTGAAACGCCCGATTTCAACGCCGCCGCAGACGATTTGTCCGCA

TTGCTTCAACCTGCCGAAGCACCGTCCGTTGAGGAAAATATAACGGAAACCGTTGCCGAA

ACACCCGACTTCAACGCCACCGCAGACGATTTGTCCGCATTACTTCAACCTTCTAAAGTA

CCTGCCGTTGAGGAAAATGCAGCGGAAACCGTTGCCGATGATTTGTCCGCACTGTTGCAA

CCTGCTGAAGCACCGGCCGTTGAGGAAAATGTAACGGAAACCGTTGCCGAAACACCCGAT

TTCAACGCCACCGCAGACGATTTGTCCGCATTACTTCAACCTTCTGAAGCACCTGCCGTT

GAGGAAAATGCAGCGGAAACCGTTGCCGATGATTTGTCCGCACTGTTGCAACCTGCTGAA

GCACCGGCCGTTGAGGAAAATGCAGCGGAAATCACTTTGGAAACGCCTGATTCCAACACC

TCTGAGGCAGACGCTTTGCCCGACTTCCTGAAAGACGGCGAGGAGGAAACGGTAGATTGG

AGCATCTACCTCTCGGAAGAAAATATCCCAAATAATGCAGATACCAGTTTCCCTTCGGAA

TCTGTAGGTTCTGACGCGCCTTCCGAAGCGAAATACGACCTTGCCGAAATGTATCTCGAA

ATCGGCGACCGCGATGCCGCTGCCGAGACAGTGCAGAAATTGCTGGAAGAAGCGGAAGGC

GACGTACTCAAACGTGCCCAAGCATTGGCGCAGGAATTGGGTATTTGA

The NBM0341 protein sequence

MPAGRLPRRCPMMTKFTDCTRSNRIQPPTHRGYILKNNRQIKLIAASVAVAASFQAHAGL

GGLNIQSNLDEPFSGSITVTGEEAKALLGGGSVTVSEKGLTAKVHKLGDKAVIAVSSEQA

VRDPVLVFRIGAGAQVREYTAILDPVGYSPKTKSALSDGKTHRKTAPTAESQENQNAKAL

RKTDKKDSANAAVKPAYNGKTHTVRKGETVKQIAAAIRPKHLTLEQVADALLKANPNVSA

HGRLRAGSVLHIPNLNRIKAEQPKPQTAKPKAETASMPSEPSKQATVEKPVEKPEAKVAA

PEAKAEKPAVRPEPVPAANTAASETAAESAPQEAAASAIDTPTDETGNAVSEPVEQVSAE

EETESGLFDGLFGGSYTLLLAGGGAALIALLLLLRLAQSKRARRTEESVPEEEPDLDDAA

DDGIEITFAEVETPATPEPAPKNDVNDTLALDGESEEELSAKQTFDVETDTPSNRIDLDF

DSLAAAQNGILSGALTQDEETQKRADADWNAIESTDSVYEPETFNPYNPVEIVIDTPEPE

SVAQTAENKPETVDTDFSDNLPSNNHIGTEETASAKPASPSGLAGFLKASSPETILEKTV

AEVQTPEELHDFLKVYETDAVAETAPETPDFNAAADDLSALLQPAEAPSVEENITETVAE

TPDFNATADDLSALLQPSKVPAVEENAAETVADDLSALLQPAEAPAVEENVTETVAETPD

FNATADDLSALLQPSEAPAVEENAAETVADDLSALLQPAEAPAVEENAAEITLETPDSNT

SEADALPDFLKDGEEETVDWSIYLSEENIPNNADTSFPSESVGSDAPSEAKYDLAEMYLE

IGDRDAAAETVQKLLEEAEGDVLKRAQALAQELGI

The NMB0338 DNA sequence

ATGGAAAGGAACGGTGTATTTGGTAAAATTGTCGGCAATCGCATACTCCGTATGTCGTCC

GAACACGCTGCCGCATCCTATCCGAAACCGTGCAAATCGTTTAAACTAGCGCAATCTTGG

TTCAGAGTGCGAAGCTGTCTGGGCGGCGTTTTTATTTACGGAGCAAACATGAAACTTATC

TATACCGTCATCAAAATCATTATCCTGCTGCTCTTCCTGCTGCTTGCCGTCATTAATACG

GATGCCGTTACCTTTTCCTACCTGCCGGGGCAAAAATTCGATTTGCCGCTGATTGTCGTA

TTGTTCGGCGCATTTGTAGTCGGTATTATTTTTGGAATGTTTGCCTTGTTCGGACGGTTG

TTGTCGTTACGTGGCGAGAACGGCAGGTTGCGTGCCGAAGTAAAGAAAAATGCGCGTTTG

ACGGGGAAGGAGCTGACCGCACCACCGGCGCAAAATGCGCCCGAATCTACCAAACAGCCT

TAA

The NMB0338 protein sequence

MERNGVFGKIVGNRILRMSSEHAAASYPKPCKSFKLAQSWFRVRSCLGGVFIYGANMKLI

YTVIKIIILLLFLLLAVINTDAVTFSYLPGQKFDLPLIVVLFGAFVVGIIFGMFALFGRL

LSLRGENGRLRAEVKKNARLTGKELTAPPAQNAPESTKQP

Analysis to polypeptide points out that prediction has two membrane spaning domains, residue 54-70 and 88-1 07.Therefore, the fragment in 1-53 and 108-terminal point (C-terminal) zone may be useful especially as immunogen.

The NMB1345 DNA sequence

ATGAAAAAACCTTTGATTTCGGTTGCGGCAGCATTGCTCGGCGTTGCTTTGGGCACGCCT

TATTATTTGGGTGTCAAAGCCGAAGAAAGCTTGACGCAGCAGCAAAAAATATTGCAGGAA

ACGGGCTTCTTGACCGTCGAATCGCACCAATATGAGCGCGGCTGGTTTACCTCTATGGAA

ACGACGGTCATCCGTCTGAAACCCGAGTTGCTGAATAATGCCCGAAAATACCTGCCGGAT

AACCTGAAAACAGTGTTGGAACAGCCGGTTACGCTGGTTAACCATATCACGCACGGCCCT

TTCGCCGGCGGATTCGGCACGCAGGCGTACATTGAAACCGAGTTCAAATACGCGCCTGAA

ACGGAAAAAGTTCTGGAACGCTTTTTTGGAAAACAAGTCCCGGCTTCCCTTGCCAATACC

GTTTATTTTAACGGCAGCGGTAAAATGGAAGTCAGTGTTCCCGCCTTCGATTATGAAGAG

CTGTCGGGCATCAGGCTGCACTGGGAAGGCCTGACGGGAGAAACGGTTTATCAAAAAGGT

TTCAAAAGCTACCGGAACGGCTATGATGCCCCCTTGTTTAAAATCAAGCTGGCAGACAAA

GGCGATGCCGCGTTTGAAAAAGTGCATTTCGATTCGGAAACTTCAGACGGCATCAATCCG

CTTGCTTTGGGCAGCAGCAATCTGACCTTGGAAAAATTCTCCCTAGAATGGAAAGAGGGT

GTCGATTACAACGTCAAGTTAAACGAACTGGTCAATCTTGTTACCGATTTGCAGATTGGC

GCGTTTATCAATCCCAACGGCAGCATCGCACCTTCCAAAATCGAAGTCGGCAAACTGGCT

TTTTCAACCAAGACCGGGGAATCAGGCGCGTTTATCAACAGTGAAGGGCAGTTCCGTTTC

GATACACTGGTGTACGGCGATGAAAAATACGGCCCGCTGGACATCCATATCGCTGCCGAA

CACCTCGATGCTTCTGCCTTAACCGTATTGAAACGCAAGTTTGCACAAATTTCCGCCAAA

AAAATGACCGAGGAACAAATCCGCAATGATTTGATTGCCGCCGTCAAAGGAGAGGCTTCC

GGACTGTTCACCAACAATCCCGTATTGGACATTAAAACTTTCCGATTCACGCTGCCATCG

GGAAAAATCGATGTGGGCGGAAAAATCATGTTTAAAGACATGAAGAAGGAAGATTTGAAT

CAATTGGGTTTGATGCTGAAGAAAACCGAAGCCGACATCAGAATGAGTATTCCCCAAAAA

ATGCTGGAAGACTTGGCGGTCAGTCAAGCAGGCAATATTTTCAGCGTCAATGCCGAAGAT

GAGGCGGAAGGCAGGGCAAGTCTTGACGACATCAACGAGACCTTGCGCCTGATGGTGGAC

AGTACGGTTCAGAGTATGGCAAGGGAAAAATATCTGACTTTGAACGGCGACCAGATTGAT

ACTGCCATTTCTCTGAAAAACAATCAGTTGAAATTGAACGGTAAAACGTTGCAAAACGAA

CCGGAGCCGGATTTTGATGAAGGCGGTATGGTTTCAGAGCCGCAGCAGTAA

The NMB1345 protein sequence

MKKPLISVAAALLGVALGTPYYLGVKAEESLTQQQKILQETGFLTVESHQYERGWFTSME

TTVIRLKPELLNNARKYLPDNLKTVLEQPVTLVNHITHGPFAGGFGTQAYIETEFKYAPE

TEKVLERFFGKQVPASLANTVYFNGSGKMEVSVPAFDYEELSGIRLHWEGLTGETVYQKG

FKSYRNGYDAPLFKIKLADKGDAAFEKVHFDSETSDGINPLALGSSNLTLEKFSLEWKEG

VDYNVKLNELVNLVTDLQIGAFINPNGSIAPSKIEVGKLAFSTKTGESGAFINSEGQFRF

DTLVYGDEKYGPLDIHIAAEHLDASALTVLKRKFAQI?SAKKMTEEQIRNDLIAAVKGEAS

GLFTNNPVLDIKTFRFTLPSGKIDVGGKIMFKDMKKEDLNQLGLMLKKTEADIRMSIPQK

MLEDLAVSQAGNIFSVNAEDEAEGRASLDDINETLRLMVDSTVQSMAREKYLTLNGDQID

TAISLKNNQLKLNGKTLQNEPEPDFDEGGMVSEPQQ

The selection of using vaccination person's serum to carry out

We obtain serum from the Meningococcal Reference Laboratory of Manchester.Described serum is from the clinical trial of volunteer OMV immunity inoculation.

The mutant of selecting by vaccination person C1 serum (screening once)

Separate and obtain following sequence:

NMB0338 (seeing above)

The NMB0738 DNA sequence

ATGAAGATCGTCCTGATTAGCGGCCTGTCCGGTTCGGGCAAGTCCGTCGCACTGCGCCAA

ATGGAAGATTCGGGTTATTTCTGCGTGGACAATTTGCCTTTGGAAATGTTGCCCGCGCTG

GTGTCGTATCATATCGAACGTGCGGACGAAACCGAATTGGCGGTCAGCGTCGATGTGCGT

TCCGGCATTGACATCGGACAGGCGCGGGAACAGATTGCCTCTCTGCGCAGACTGGGGCAC

AGGGTTGAAGTTTTGTTTGTCGAGGCGGAAGAAAGCGTGTTGGTCCGCCGGTTTTCCGAA

ACCAGGCGAGGACATCCTCTGAGCAATCAGGATATGACCTTGTTGGAAAGCTTAAAGAAA

GAACGGGAATGGCTGTTCCCGCTTAAAGAAATCGCCTATTGTATCGACACTTCCAAGATG

AATGCCCAACAGCTCCGCCATGCAGTCCGGCAGTGGCTGAAGGTCGAACGTACCGGGCTG

CTGGTGATTTTGGAGTCCTTCGGGTTCAAATACGGTGTGCCGAACAACGCGGATTTTATG

TTCGATATGCGCAGCCTGCCCAACCCGTATTACGATCCCGAGTTGAGGCCTTACACCGGT

ATGGACAAGCCCGTTTGGGATTATTTGGACGGACAGCCGCTTGTGCAGGAAATGGTTGAC

GACATCGAAAGGTTTGTTACGCATTGGTTACCGCGTTTGGAGGATGAAAGCAGGAGCTAC

GTTACCGTCGCCATCGGTTGCACGGGAGGACAGCACCGTTCGGTCTATATTGTCGAAAAA

CTCGCCCGAAGGTTGAAAGGGCGTTATGAATTGCTGATACGGCACAGACAGGCGCAAAAC

CTGTCAGACCGCTAA

The NMB0738 protein sequence

MKIVLISGLSGSGKSVALRQMEDSGYFCVDNLPLEMLPALVSYHIERADETELAVSVDVR

SGIDIGQAREQIASLRRLGHRVEVLFVEAEESVLVRRFSETRRGHPLSNQDMTLLESLKK

EREWLFPLKEIAYCIDTSKMNAQQLRHAVRQWLKVERTGLLVILESFGFKYGVPNNADFM

FDMRSLPNPYYDPELRPYTGMDKPVWDYLDGQPLVQEMVDDIERFVTHWLPRLEDESRSY

VTVAIGCTGGQHRSVYIVEKLARRLKGRYELLIRHRQAQNLSDR

NMB0792 NadC family (transport protein) DNA sequence

ATGAACCTGCATGCAAAGGACAAAACCCAGCATCCCGAAAACGTCGAGCTGCTCAGTGCG

CAGAAGCCGATTACCGACTTTAAGGGCCTGCTGACCACCATTATTTCCGCCGTCGTCTGT

TTCGGCATTTACCACATCCTGCCTTACAGCCCCGATGCCAATAAAGGTATCGCGCTGCTG

ATTTTCGTTGCCGCACTTTGGTTTACCGAGGCCGTCCACATTACCGTAACCGCACTGATG

GTGCCGATTCTCGCCGTCGTACTCGGTTTCCCCGACATGGACATCAAAAAGGCGATGGCT

GATTTTTCCAACCCGATTATCTACATTTTTTTCGGCGGCTTCGCGCTTGCCACCGCCCTG

CATATGCAGCGGCTGGACCGTAAAATCGCCGTCAGCCTGTTGCGCCTGTCGCGCGGCAAT

ATGAAAGTGGCGGTTTTGATGTTGTTCCTCGTTACCGCCTTTCTGTCCATGTGGATCAGC

AACACCGCCACCGCCGCGATGATGCTGCCTCTAGCAATGGGTATGCTGAGCCACCTCGAC

CAGGAAAAAGAACACAAAACCTACGTCTTCCTCCTGCTCGGCATCGCCTATTGCGCCAGC

ATCGGCGGCTTGGGCACGCTCGTCGGCTCGCCGCCCAACCTGATTGCCGCCAAAGCCCTA

AATCTGGACTTCGTCGGCTGGATGAAGCTCGGCCTGCCGATGATGCTGTTGATTCTGCCC

TTGATGCTGCTCTCCCTGTACGTCATCCTCAAACCTAATTTGAACGAACGCGTGGAAATC

AAAGCCGAATCCATCCCTTGGACGCTGCACCGCGTGATCGCGCTGTTGATTTTCCTTGCC

ACAGCCGCCGCGTGGATATTCAGCTCCAAAATCAAAACCGCCTTCGGCATTTCCAATCCC

GACACCGTTATCGCCCTGAGTGCCGCCGTCGCCGTCGTCGTCTTCGGCGTGGCGCAATGG

AAGGAAGTCGCCCGCAATACCGACTGGGGCGTGTTGATGCTCTTCGGCGGCGGCATCAGC

CTGAGCACGCTGTTGAAAACATCCGGCGCGTCCGAAGCCTTGGGACAGCAGGTTGCCGCC

ACCTTTTCCGGCGCGCCCGCATTTTTGGTGATACTCATCGTCGCCGCCTTCATTATTTTT

CTGACCGAGTTCACCAGCAACACCGCCTCCGCCGCATTGCTTGTACCGATTTTCTCCGGC

ATCGCTATGCAGATGGGGCTGCCCGAACAAGTCTTGGTATTCGTCATCGGCATCGGCGCA

TCTTGTGCCTTCATGCTGCCGGTTGCCACACCGCCTAACGCGATTGTGTTCGGCACGGGC

TTAATCAAGCAACGCGAAATGATGAATGTCGGCATACTGCTGAACATCCTCTGCGTAGTA

TTGGTTGCTCTGTGGGCTTATGCTGTACTGATGTAA

The NMB0792 protein sequence

MNLHAKDKTQHPENVELLSAQKPITDFKGLLTTIISAVVCFGIYHILPYSPDANKGIALL

IFVAALWFTEAVHITVTALMVPILAVVLGFPDMDIKKAMADFSNPIIYIFFGGFALATAL

HMQRLDRKIAVSLLRLSRGNMKVAVLMLFLVTAFLSMWISNTATAAMMLPLAMGMLSHLD

QEKEHKTYVFLLLGIAYCASIGGLGTLVGSPPNLIAAKALNLDFVGWMKLGLPMMLLILP

LMLLSLYVILKPNLNERVEIKAESIPWTLHRVIALLIFLATAAAWIFSSKIKTAFGISNP

DTVIALSAAVAVVVFGVAQWKEVARNTDWGVLMLFGGGISLSTLLKTSGASEALGQQVAA

TFSGAPAFLVILIVAAFIIFLTEFTSNTASAALLVPIFSGIAMQMGLPEQVLVFVIGIGA

SCAFMLPVATPPNAIVFGTGLIKQREMMNVGILLNILCVVLVALWAYAVLM

The NMB0279 DNA sequence

ATGCAACGACAAATCAAACTGAAAAATTGGCTTCAGACCGTTTATCCCGAACGGGACTTC

GATCTGACTTTTGCGGCGGCGGATGCTGATTTCCGCCGCTATTTCCGTGCAACGTTTTCA

GACGGCAGCAGTGTCGTCTGCATGGATGCACCGCCCGACAAGATGAGTGTCGCACCTTAT

TTGAAAGTGCAGAAACTGTTTGACATGGTCAATGTGCCGCAGGTATTGCACGCGGACACG

GATCTGGGGTTTGTGGTATTGAACGACTTGGGCAATACGACGTTTTTGACCGCAATGCTT

CAGGAACAGGGCGAAACGGCGCACAAAGCCCTGCTTTTGGAGGCAATCGGCGAGTTGGTC

GAATTGCAGAAGGCGAGCCGTGAAGGGGTTTTGCCCGAATATGACCGTGAAACGATGTTG

CGCGAAATCAACCTGTTCCCGGAATGGTTTGTCGCAAAAGAATTGGGGCGCGAATTAACA

TTCAAACAACGCCAACTTTGGCAGCAAACCGTCGATACGCTGCTGCCGCCCCTGTTGGCG

CAGCCCAAAGTCTATGTGCACCGCGACTTTATCGTCCGCAACCTGATGCTGACGCGCGGC

AGGCCGGGCGTTTTAGACTTCCAAGACGCGCTTTACGGCCCGATTTCCTACGATTTGGTG

TCGCTGTTGCGCGATGCCTTTATCGAATGGGAAGAAGAATTTGTCTTGGACTTGGTTATC

CGCTACTGGGAAAAGGCGCGGGCTGCCGGCTTGCCCGTCCCCGAAGCGTTTGACGAGTTT

TACCGCTGGTTCGAATGGATGGGCGTGCAGCGGCACTTGAAGGTTGCAGGCATCTTCGCA

CGCCTGTACTACCGCGACGGCAAAGACAAATACCGTCCGGAAATCCCGCGTTTCTTAAAC

TATCTGCGCCGCGTATCGCGCCGTTATGCCGAACTCGCCCCGCTCTACGCGCTCTTGGTC

GAACTGGTCGGCGATGAAGAACTGGAAACGGGCTTTACGTTTTAA

The NMB0279 protein sequence

MQRQIKLKNWLQTVYPERDFDLTFAAADADFRRYFRATFSDGSSVVCMDAPPDKMSVAPY

LKVQKLFDMVNVPQVLHADTDLGFVVLNDLGNTTFLTAMLQEQGETAHKALLLEAIGELV

ELQKASREGVLPEYDRETMLREINLFPEWFVAKELGRELTFKQRQLWQQTVDTLLPPLLA

QPKVYVHRDFIVRNLMLTRGRPGVLDFQDALYGPISYDLVSLLRDAFIEWEEEFVLDLVI

RYWEKARAAGLPVPEAFDEFYRWFEWMGVQRHLKVAGIFARLYYRDGKDKYRPEIPRFLN

YLRRVSRRYAELAPLYALLVELVGDEELETGFTF

The NMB2050 DNA sequence

ATGGAACTGATGACTGTTTTGCTGCCTTTGGCGGCGTTGGTGTCGGGCGTGTTGTTTACA

TGGTTGCTGATGAAGGGCCGGTTTCAGGGCGAGTTTGCCGGTTTGAACGCGCACCTGGCG

GAAAAGGCGGCAAGATGTGATTTTGTCGAACAGGCACACGGCAAAACCGTGTCGGAATTG

GCGGTGTTGGACGGGAAATACCGGCATTTGCAGGACGAAAATTATGCTTTGGGCAACCGT

TTTTCCGCAGCCGAAAAGCAGATTGCCCATTTGCAGGAAAAAGAGGCGGAGTCGGCGCGG

CTGAAGCAGTCGTATATCGAGTTGCAGGAAAAGGCACAGGGTTTGGCGGTTGAAAACGAA

CGTTTGGCAACGCAGCTCGGACAGGAACGGAAGGCGTTTGCCGACCAATATGCCTTGGAA

CGCCAAATCCGCCAAAGAATCGAAACCGATTTGGAAGAAAGCCGCCAAACTGTCCGCGAC

GTGCAAAACGACCTTTCCGATGTCGGCAACCGTTTTGCCGCAGCCGAAAAACAGATTGCC

CATTTGCAGGAAAAAGAGGCGGAAGCGGAGCGGTTGAGGCAGTCGCATACCGAGTTGCAG

GAAAAGGCACAGGGTTTGGCGGTTGAAAACGAACGTTTGGCAACGCAAATCGAACAGGAA

CGCCTTGCTTCTGAAGAGAAGCTGTCCTTGCTGGGCGAGGCGCGCAAAAGTTTGAGCGAT

CAGTTTCAAAATCTTGCCAACACGATTTTGGAAGAAAAAAAGCCGCCGTTTTACCGAGCAG

AACCGCGAGCAGCTCCATCAGGTTTTGAACCCGCTAAACGAACGCATCCACGGTTTCGGC

GAGTTGGTCAAGCAAACCTATGATAAAGAATCGCGCGAGCGGCTGACGTTGGAAAACGAA

TTGAAACGGCTTCAGGGGTTGAACGCGCAGCTGCACAGCGAGGCAAAGGCCCTGACCAAC

GCGCTGACCGGTACGCAGAATAAGGTTCAGGGCAATTGGGGCGAGATGATTCTGGAAACG

GTTTTGGAAAATTCCGGCCTTCAGAAAGGGCGGGAATATGTGGTTCAGGCGGCATCCGTC

CGAAAAGAGGAAGACGGCGGCACGCGCCGCCTCCAGCCCGACGTTTTGGTCAACCTGCCC

GACAACAAGCAGATTGTGATTGATTCCAAGGTCTCGCTGACAGCTTATGTGCGCTACACG

CAGGCGGCGGATGCGGATACGGCGGCACGCGAACTGGCGGCACACGTTGCCAGCATCCGT

GCACACATGAAAGGCTTGTCGCTGAAGGATTACACCGATTTGGAAGGTGTGAACACATTG

GATTTCGTCTTTATGTTTATCCCTGTCGAACCGGCCTACCTGTTGGCGTTGCAGAATGAC

GCGGGCTTGTTCCAAGAGTGTTTCGACAAACGGATTATGCTGGTCGGCCCCAGTACGCTG

CTGGCGACTTTGAGGACGGTGGCGAATATTTGGCGCAACGAACAGCAAAATCAGAACGCA

CTGGCGATTGCGGACGAAGGCGGCAAGCTGTACGACAAGTTTGTCGGCTTCGTACAGACG

CTCGAAAGCGTCGGCAAAGGCATCGATCAGGCGCAAAGCAGTTTTCAGACGGCATTCAAG

CAACTTGCCGAAGGGCGCGGGAATCTGGTCGGACGCGCCGAGAAACTGCGTCTGTTGGGC

GTGAAGGCAGGCAAACAACTTCAACGGGATTTGGTCGAGCGTTCCAATGAAACAACGGCG

TTGTCGGAATCTTTGGAATACGCGGCAGAAGATGAAGCAGTCTGA

The NMB2050 protein sequence

MELMTVLLPLAALVSGVLFTWLLMKGRFQGEFAGLNAHLAEKAARCDFVEQAHGKTVSEL

AVLDGKYRHLQDENYALGNRFSAAEKQIAHLQEKEAESARLKQSYIELQEKAQGLAVENE

RLATQLGQERKAFADQYALERQIRQRIETDLEESRQTVRDVQNDLSDVGNRFAAAEKQIA

HLQEKEAEAERLRQSHTELQEKAQGLAVENERLATQIEQERLASEEKLSLLGEARKSLSD

QFQNLANTILEEKSRRFTEQNREQLHQVLNPLNERIHGFGELVKQTYDKESRERLTLENE

LKRLQGLNAQLHSEAKALTNALTGTQNKVQGNWGEMILETVLENSGLQKGREYVVQAASV

RKEEDGGTRRLQPDVLVNLPDNKQIVIDSKVSLTAYVRYTQAADADTAARELAAHVASIR

AHMKGLSLKDYTDLEGVNTLDFVFMFIPVEPAYLLALQNDAGLFQECFDKRIMLVGPSTL

LATLRTVANIWRNEQQNQNALAIADEGGKLYDKFVGFVQTLESVGKGIDQAQSSFQTAFK

QLAEGRGNLVGRAEKLRLLGVKAGKQLQRDLVERSNETTALSESLEYAAEDEAV

NMB1335 CreA protein D NA sequence

ATGAACAGACTGCTACTGCTGTCTGCCGCCGTCCTGCTGACTGCCTGCGGCAGCGGCGAA

ACCGATAAAATCGGACGGGCAAGTACCGTTTTCAACATACTGGGCAAAAACGACCGTATC

GAAGTGGAAGGATTCGACGATCCCGACGTTCAAGGGGTTGCCTGTTATATTTCGTATGCA

AAAAAAGGCGGCTTGAAGGAAATGGTCAATTTGGAAGAGGACGCGTCCGACGCATCGGTT

TCGTGCGTTCAGACGGCATCTTCGATTTCTTTTGACGAAACCGCCGTGCGCAAACCGAAA

GAAGTTTTCAAACACGGTGCGAGCTTCGCGTTCAAGAGCCGGCAGATTGTCCGTTATTAC

GACCCCAAACGCAAAACCTTCGCCTATTTGGTGTACAGCGATAAAATCATCCAAGGCTCG

CCGAAAAATTCCTTAAGCGCGGTTTCCTGTTTCGGCGGCGGCATACCGCAAACCGATGGG

GTGCAAGCCGATACTTCCGGCAACCTGCTTGCCGGCGCCTGCATGATTTCCAACCCGATA

GAAAATCTCGACAAACGCTGA

The NMB1335 protein sequence

MNRLLLLSAAVLLTACGSGETDKIGRASTVFNILGKNDRIEVEGFDDPDVQGVACYISYA

KKGGLKEMVNLEEDASDASVSCVQTASSISFDETAVRKPKEVFKHGASFAFKSRQIVRYY

DPKRKTFAYLVYSDKIIQGSPKNSLSAVSCFGGGIPQTDGVQADTSGNLLAGACMISNPI

ENLDKR

The NMB2035 DNA sequence

ATGACCGCCTTTGTCCACACCCTTTCAGACGGCATGGAACTGACCGTCGAAATCAAGCGC

CGTGCCAAGAAAAACCTGATTATCCGCCCCGCCGGCACACATACCGTCCGCATCAGCGTC

CCACCCTGCTTCTCCGTCTCCGCTCTAAACCGCTGGCTGTATGAAAACGAAGCCGTCCTG

CGGCAAACACTGGCGAAAACACCGCCGCCGCAAACTGCCGAAAACCGGCTGCCCGAATCC

ATCCTCTTCCACGGCAGACAGCTTGCCCTCACCGCCCATCAAGACACGCAAATCCTGCTG

ATGCCGTCTGAAATCCGTGTTCCCGAAGGCGCACCCGAAAAACAGCTTGCGCTGCTGCGG

GACTTTTTGGAACGGCAGGCGCACAGTTACCTGATTCCCCGCCTCGAACGCCACGCCCGC

ACCACACAACTGTTCCCCGCCTCCTCCTCGCTGACCTCTGCCAAAACCTTCTGGGGCGTG

TGCCGCAAAACCACAGGCATACGCTTCAACTGGCGGCTGGTCGGCGCACCGGAATACGTT

GCCGACTATGTCTGCATACACGAACTCTGCCACCTCGCCCATCCCGACCACAGCCCCGCC

TTTTGGGAACTGACCCGCCGCTTCGCCCCCTACACGCCCAAAGCGAAACAGTGGCTCAAA

ATCCACGGCAGGGAACTTTTCGCCTTAGGCTGA

The NMB2035 protein sequence

MTAFVHTLSDGMELTVEIKRRAKKNLIIRPAGTHTVRISVPPCFSVSALNRWLYENEAVL

RQTLAKTPPPQTAENRLPESILFHGRQLALTAHQDTQILLMPSEIRVPEGAPEKQLALLR

DFLERQAHSYLIPRLERHARTTQLFPASSSLTSAKTFWGVCRKTTGIRFNWRLVGAPEYV

ADYVCIHELCHLAHPDHSPAFWELTRRFAPYTPKAKQWLKIHGRELFALG

NMB1351Fmu and Fmv protein D NA sequence

ATGAACGCCGCACAACTCGACCATACCGCCAAAGTTTTGGCTGAAATGCTGACTTTCAAA

CAGCCTGCCGATGCCGTCCTCTCCGCCTATTTCCGCGAACACAAAAAGCTCGGCAGTCAA

GATCGCCACGAAATCGCCGAAACCGCCTTTGCCGCGCTGCGCCACTATCAAAAAATCAGT

ACCGCCCTACGCCGTCCGCACGCGCAGCCGCGCAAAGCCGCTCTCGCCGCACTGGTTCTC

GGCAGAAGCACCAACATCAGCCAAATCAAAGACCTGCTTGATGAAGAAGAAACAGCGTTC

CTCGGCAATTTGAAAGCCCGTAAAACCGAGTTTTCAGACAGCCTGAATACCGCCGCAGAA

TTGCCGCAATGGCTGGTGGAACAACTGAAACAGCATTGGCGCGAAGAAGAAATCCTCGCT

TTCGGCCGCAGCATCAACCAGCCTGCCCCGCTCGACATCCGCGTCAACACTTTGAAAGGC

AAACGCGATAAAGTGCTGCCGCTGTTGCAAGCCGAAAGTGCCGATGCAGAGGCAACGCCT

TATTCGCCTTGGGGCATCCGCCTGAAAAACAAAATCGCGCTTAACAAACACGAACTGTTT

TTAGACGGCACACTGGAAGTCCAAGACGAAGGCAGCCAGCTGCTTGCCTTATTGGTGGGC

GCAAAACGAGGCGAAATCATTGTCGATTTCTGTGCCGGTGCCGGCGGTAAAACCTTGGCT

GTCGGTGCGCAAATGGCGAACAAAGGCAGAATCTACGCCTTCGATATCGCCGAAAAACGC

CTTGCCAACCTCAAACCGCGTATGACCCGCGCCGGACTGACCAATATCCACCCCGAACGC

ATCGGCAGCGAACACGATGCCCGTATCGCCCGACTGGCAGGCAAAGCCGACCGTGTGTTG

GTGGACGCGCCCTGCTCCGGTTTGGGCACTTTACGCCGCAATCCCGACCTCAAATACCGC

CAATCCGCCGAAACCGTCGCCAACCTTTTGGAACAGCAACACAGCATCCTCGATGCCGCC

TCCAAACTGGTAAAACCGCAAGGACGTTTGGTGTACGCCACTTGCAGCATCCTGCCCGAA

GAAAACGAGCTGCAAGTCGAACGTTTCCTGTCCGAACATCCCGAATTTGAACCCGTCAAC

TGCGCCGAACTGCTTGCCGGTTTGAAAATCGATTTGGATACCGGCAAATACCTGCGCCTC

AACTCCGCCCGACACCAAACCGACGGCTTCTTCGCCGCCGTATTGCAACGCAAATAA

The NMB1351 protein sequence

MNAAQLDHTAKVLAEMLTFKQPADAVLSAYFREHKKLGSQDRHEIAETAFAALRHYQKIS

TALRRPHAQPRKAALAALVLGRSTNISQIKDLLDEEETAFLGNLKARKTEFSDSLNTAAE

LPQWLVEQLKQHWREEEILAFGRSINQPAPLDIRVNTLKGKRDKVLPLLQAESADAEATP

YSPWGIRLKNKIALNKHELFLDGTLEVQDEGSQLLALLVGAKRGEIIVDFCAGAGGKTLA

VGAQMANKGRIYAFDIAEKRLANLKPRMTRAGLTNIHPERIGSEHDARIARLAGKADRVL

VDAPCSGLGTLRRNPDLKYRQSAETVANLLEQQHSILDAASKLVKPQGRLVYATCSILPE

ENELQVERFLSEHPEFEPVNCAELLAGLKIDLDTGKYLRLNSARHQTDGFFAAVLQRK

The NMB1574IlvC DNA sequence

ATGCAAGTCTATTACGATAAAGATGCCGATCTGTCCCTAATCAAAGGCAAAACCGTTGCC

ATCATCGGTTACGGTTCGCAAGGTCATGCCCATGCCGCCAACCTGAAAGATTCGGGTGTA

AACGTGGTGATTGGTCTGCGCCAAGGTTCTTCTTGGAAAAAAGCCGAAGCAGCCGGTCAT

GTCGTCAAAACCGTTGCTGAAGCGACCAAAGAAGCCGATGTCGTTATGCTGCTGCTGCCT

GACGAAACCATGCCTGCCGTCTATCACGCCGAAGTTACAGCCAATTTGAAAGAAGGCGCA

ACGCTGGCATTTGCACACGGCTTCAACGTGCACTACAACCAAATCGTTCCGCGTGCCGAC

TTGGACGTGATTATGGTTGCCCCCAAAGGTCCGGGCCATACCGTACGCAGTGAATACAAA

CGCGGCGGCGGCGTGCCTTCTCTGATTGCCGTTTACCAAGACAATTCCGGCAAAGCCAAA

GACATCGCCCTGTCTTATGCGGCTGCCAACGGCGGCACCAAAGGCGGTGTGATTGAAACC

ACTTTCCGCGAAGAAACCGAAACCGATCTGTTCGGCGAACAAGCCGTATTGTGCGGCGGC

GTGGTCGAGTTGATCAAGGCGGGTTTTGAAACCCTGACCGAAGCCGGTTACGCGCCTGAA

ATGGCTTACTTCGAATGTCTGCACGAAATGAAACTGATCGTTGACCTGATTTTCGAAGGC

GGTATTGCCAATATGAACTACTCCATTTCCAACAATGCGGAGTACGGCGAATACGTTACC

GGCCCTGAAGTGGTCAATGCTTCCAGCAAAGAAGCCATGCGCAATGCCCTGAAACGCATT

CAAACCGGCGAATACGCAAAAATGTTTATCCAAGAGGGTAATGTCAACTATGCGTCTATG

ACTGCCCGCCGCCGTCTGAATGCCGACCACCAAGTTGAAAAAGTCGGCGCACAACTGCGT

GCCATGATGCCTTGGATTACTGCCAACAAATTGGTTGACCAAGACAAAAACTGA

The NMB1574 protein sequence

MQVYYDKDADLSLIKGKTVAIIGYGSQGHAHAANLKDSGVNVVIGLRQGSSWKKAEAAGH

VVKTVAEATKEADVVMLLLPDETMPAVYHAEVTANLKEGATLAFAHGFNVHYNQIVPRAD

LDVIMVAPKGPGHTVRSEYKRGGGVPSLIAVYQDNSGKAKDIALSYAAANGGTKGGVIET

TFREETETDLFGEQAVLCGGVVELIKAGFETLTEAGYAPEMAYFECLHEMKLIVDLIFEG

GIANMNYSISNNAEYGEYVTGPEVVNASSKEAMRNALKRIQTGEYAKMFIQEGNVNYASM

TARRRLNADHQVEKVGAQLRAMMPWITANKLVDQDKN

NMB1298 rsuADNA sequence

ATGAAACTTATCAAATACCTGCAATATCAAGGCATAGGAAGCCGCAAGCAGTGCCAATGG

CTGATTGCCGGCGGTTATGTTTTCATCAACGGAACCTGCATGGACGACACCGATGCAGAC

ATCGATTCCTCATCCGTCGAAACGTTGGATATTGACGGGGAAGCAGTAACCGTCGTTCCC

GAACCCTATTTCTACATCATGCTCAACAAGCCTGAAGATTACGAAACTTCGCACAAACCC

AAGCACTACCGCAGCGTATTCAGCCTGTTCCCCGACAATATGCGGAACATCGATATGCAG

GCGGTCGGCAGGCTGGATGCAGATACGACCGGCGTATTGCTGATTACCAACGACGGCAAA

CTGAACCACAGCCTGACTTCGCCGAGCAGAAAAATTCCCAAGCTGTACGAAGTAACGCTC

AAACACCCCACAGGAGAAACGCTCTGCGAAACCTTGAAAAACGGCGTGCTGCTCCACGAC

GAAAACGAAACCGTTTGTGCCGCCGATGCCGTTTTGAAAAACCCGACCACCCTGCTGCTG

ACCATTACCGAAGGAAAATACCACCAAGTCAAACGCATGATCGCCGCCGCCGGCAACCGC

GTGCAACACCTTCATCGCCGGCGATTCGCACATCTGGAAACAGAAAACCTCAAACCCGGG

GAATGGAAATTTATCGAATGTCCAAAATTCTGA

The NMB1298 protein sequence

MKLIKYLQYQGIGSRKQCQWLIAGGYVFINGTCMDDTDADIDSSSVETLDIDGEAVTVVP

EPYFYIMLNKPEDYETSHKPKHYRSVFSLFPDNMRNIDMQAVGRLDADTTGVLLITNDGK

LNHSLTSPSRKIPKLYEVTLKHPTGETLCETLKNGVLLHDENETVCAADAVLKNPTTLLL

TITEGKYHQVKRMIAAAGNRVQHLHRRRFAHLETENLKPGEWKFIECPKF

NMB1856 Lys R family (transcription regulating and controlling article) DNA sequence

ATGAAAACCAATTCAGAAGAACTGACCGTATTTGTTCAAGTGGTGGAAAGCGGCAGCTTC

AGCCGTGCGGCGGAGCAGTTGGCGATGGCAAATTCTGCCGTAAGCCGCATCGTCAAACGG

CTGGAGGAAAAGTTGGGTGTGAACCTGCTCAACCGCACCACGCGGCAACTCAGTCTGACG

GAAGAAGGCGCGCAATATTTCCGCCGCGCGCAGAGAATCCTGCAAGAAATGGCAGCGGCG

GAAACCGAAATGCTGGCAGTGCACGAAATACCGCAAGGCGTGTTGAGCGTGGATTCCGCG

ATGCCGATGGTGCTGCATCTGCTGGCGCCGCTGGCAGCAAAATTCAACGAACGCTATCCG

CATATCCGACTTTCGCTCGTTTCTTCCGAAGGCTATATCAATCTGATTGAACGCAAAGTC

GATATTGCCTTACGGGCCGGAGAATTGGACGATTCCGGGCTGCGTGCACGCCATCTGTTT

GACAGCCGCTTCCGCGTAATCGCCAGTCCTGAATACCTGGCAAAACACGGCACGCCGCAA

TCTACAGAAGAGCTTGCCGGCCACCAATGTTTAGGCTTCACCGAACCCGGTTCTCTAAAT

ACATGGGCGGTTTTAGATGCGCAGGGAAATCCCTATAAGATTTCACCGCACTTTACCGCC

AGCAGCGGTGAAATCTTACGCTCGTTGTGCCTTTCAGGTTGCGGTATTGTTTGCTTATCA

GATTTTTTGGTTGACAACGACATCGCTGAAGGAAAGTTAATTCCCCTGCTCGCCGAACAA

ACCTCCGATAAAACACACCCCTTTAATGCTGTTTATTACAGCGATAAAGCCGTCAATCTC

CGCTTACGCGTATTTTTGGATTTTTTAGTGGAGGAACTGGGAAACAATCTCTGTGGATAA

The NMB1856 protein sequence

MKTNSEELTVFVQVVESGSFSRAAEQLAMANSAVSRIVKRLEEKLGVNLLNRTTRQLSLT

EEGAQYFRRAQRILQEMAAAETEMLAVHEIPQGVLSVDSAMPMVLHLLAPLAAKFNERYP

HIRLSLVSSEGYINLIERKVDIALRAGELDDSGLRARHLFDSRFRVIASPEYLAKHGTPQ

STEELAGHQCLGFTEPGSLNTWAVLDAQGNPYKISPHFTASSGEILRSLCLSGCGIVCLS

DFLVDNDIAEGKLIPLLAEQTSDKTHPFNAVYYSDKAVNLRLRVFLDFLVEELGNNLCG

The NMB0119 DNA sequence

ATGATGAAGGATTTGAATTTGAGCAACAGCCTGTTCAAAGGCTACAACGACAAACATGGC

TTAATGATTTGTGGCTATGAATGGGGTTGGAGTAAAGCCGATGAGGCTGCTTATGTAGCA

GGTGAATACAAACTCCCTGAAAACAAAATCGACCATACATTTGCAAACAAATCCCTCTAT

TTCGGAGAGCAGGCAAAAAAGTGGCGTTACGACAATACGATAAAAAATTGGTTTGAAATG

TGGGGACACCCCTTAGACGAAAATGGATTGGGCGGTGCATTTGAAAAATCCCTGGTTCAA

ACCAACTGGGCTGCTACACAGGGCAACACTATCGACAATCCCGACAAGTTCACACAACCC

GAGCACATCGATAATTTTCTCTACCACATCGAAAAACTGCGTCCGAAAGTCATCCTCTTC

ATGGGCAGCAGGTTGGCGGATTTTCTGAACAACCAAAATGTACTGCCACGCTTCGAGCAG

TTGGTCGGTAAGCAGACCAAACCGCTGGAGACGGTGCAAAAAGAATTTGACGGTACACGT

TTCAATGTCAAATTCCAATCGTTTGAAGATTGCGAAGTCGTCTGCTTTCCCCATCCCAGT

GCCAGTCGCGGTCTATCTTACGATTACATCGCCTTGTTTGCGCCTGAAATGAACCGGATT

TTATCGGACTTTAAAACAACACGCGGATTCAAATAA

The NMB0119 protein sequence

MMKDLNLSNSLFKGYNDKHGLMICGYEWGWSKADEAAYVAGEYKLPENKIDHTFANKSLY

FGEQAKKWRYDNTIKNWFEMWGHPLDENGLGGAFEKSLVQTNWAATQGNTIDNPDKFTQP

EHI?DNFLYHIEKLRPKVILFMGSRLADFLNNQNVLPRFEQLVGKQTKPLETVQKEFDGTR

FNVKFQSFEDCEVVCFPHPSASRGLSYDYIALFAPEMNRILSDFKTTRGFK

NMB1705 rfaK DNA sequence

ATGGAAAAAGAATTCAGGATATTAAATATCGTATCGGCCAAGATTTGGGGTGGAGGCGAA

CAATATGTCTATGATGTTTCAAAAGCATTGGGGCTTCGGGGCTGCACAATGTTTACCGCC

GTCAATAAAAATAATGAATTGATGCACAGGCGATTTTCCGAAGTTTCTTCCGTTTTCACA

ACGCGCCTTCACACGCTCAACGGGCTGTTTTCGCTCTACGCACTTACCCGCTTTATCCGG

AAAAACCGCATTTCCCACCTGATGATACACACCGGCAAAATTGCCGCCTTATCCATACTT

TTGAAAAAACTGACCGGGGTGCGCCTGATATTTGTCAAACATAATGTCGTCGCCAACAAA

ACCGATTTTTACCACCGCCTGATACAGAAAAACACAGACCGCTTTATTTGCGTTTCCCGT

CTGGTTTACGATGTGCAAACCGCCGACAATCCCTTTAAAGAAAAATACCGGATTGTTCAT

AACGGTATCGATACCGGCCGTTTCCCTCCCTCTCAAGAAAAACCCGACAGCCGTTTTTTT

ACCGTCGCCTACGCCGGCAGGATCAGTCCAGAAAAAGGATTGGAAAACCTGATTGAAGCC

TGTGTGATACTGCATCGGAAATATCCTCAAATCAGGCTCAAATTGGCAGGGGACGGACAT

CCGGATTATATGTGCCGCCTGAAGCGGGACGTATCTGCTTCAGGAGCAGAACCATTTGTT

TCTTTTGAAGGGTTTACCGAAAAACTTGCTTCGTTTTACCGCCAAAGCGATGTCGTGGTT

TTGCCCAGCCTCGTCCCGGAGGCATTCGGTTTGTCATTATGCGAGGCGATGTACTGCCGA

ACGGCGGTGATTTCCAATACTTTGGGGGCGCAAAAGGAAATTGTCGAACATCATCAATCG

GGGATTCTGCTGGACAGGCTGACACCTGAATCTTTGGCGGACGAAATCGAACGCCTCGTC

TTGAACCCTGAAACGAAAAACGCACTGGCAACGGCAGCTCATCAATGCGTCGCCGCCCGT

TTTACCATCAACCATACCGCCGACAAATTATTGGATGCAATATAA

The NMB1705 protein sequence

MEKEFRILNIVSAKIWGGGEQYVYDVSKALGLRGCTMFTAVNKNNELMHRRFSEVSSVFT

TRLHTLNGLFSLYALTRFIRKNRISHLMIHTGKIAALSILLKKLTGVRLIFVKHNVVANK

TDFYHRLIQKNTDRFICVSRLVYDVQTADNPFKEKYRIVHNGIDTGRFPPSQEKPDSRFF

TVAYAGRISPEKGLENLIEACVILHRKYPQIRLKLAGDGHPDYMCRLKRDVSASGAEPFV

SFEGFTEKLASFYRQSDVVVLPSLVPEAFGLSLCEAMYCRTAVISNTLGAQKEIVEHHQS

GILLDRLTPESLADEIERLVLNPETKNALATAAHQCVAARFTINHTADKLLDAI

NMB2065 Hemk protein D NA sequence

ATGCAGGAACAGAATCGGAAACCAAGTTTTCCCATAGTGATGTTGCTGGTGTCGGTTGCC

CTGTGGATAGCGTCTTTATCCAATGTTGCATTTTATTTGGGCAATCATGGAAGCATGGAG

GGTTTGACCGTTTTGATTTTGGGGTCGATATTTGCTTCTTTGGATATCAGGTATTGTGCG

GTCTATGCGAATTATGTTTGGTTGGCGGCCATTGTTTTGCTGGCGTTGCGGAAGAAGGTC

GTGCCTGTCCATGCGGCACTTTGGGGCTTGGCGTTGGTGGCTTTCAGTGTGAAAGCCGTA

TACGTCGATGAAGCAGGGAATACATCGGATATTGTGCGCTACGGTGCAGGATTTTATTTG

TGGTATGCCGCATTTGCGGTTGCCACCATCGGTACGTTTGCCGGAAAGAATAAGGAAAGA

AAAGCCGCATCAGCGGCAGACGGGATAAAAATGACGTTTGATAAATGGTTGGGCTTGTCA

AAACTGCCTAAAAATGAAGCAAGAATGCTGCTACAATATGTTTCGGAATATACGCGCGTG

CAGTTGTTGACGCGGGGCGGGGAAGAAATGCCGGACGAAGTCCGACAGCGGGCGGACAGG

CTGGCGCAACGCCGTCTGAACGGCGAGCCGGTTGCCTATATTTTAGGTGTGCGCGAATTT

TATGGCAGACGCTTTACAGTCAATCCGAGCGTGCTGATTCCGCGCCCCGAAACCGAACAT

TTGGTCGAAGCCGTATTGGCGCGCCTGCCCGAAAACGGGCGCGTGTGGGATTTGGGGACG

GGCAGCGGCGCGGTTGCCGTAACCGTCGCGCTCGAACGCCCCGATGCGTTTGTGCGCGCA

TCCGACATCAGCCCGCCCGCCCTTGAAACGGCGCGGAAAAATGCGGCGGATTTGGGCGCG

CGGGTCGAATTTGCACACGGTTCGTGGTTCGACACCGATATGCCGTCTGAAGGGAAATGG

GACATCATCGTGTCCAACCCGCCCTATATCGAAAACGGCGATAAACATTTGTTGCAAGGC

GATTTGCGGTTTGAGCCGCAAATCGCGCTGACCGACTTTTCAGACGGCCTAAGCTGCATC

CGCACCTTGGCGCAAGGCGCGCCCGACCGTTTGGCGGAAGGCGGTTTTTTATTGCTGGAA

CACGGTTTCGATCAGGGCGCGGCGGTGCGCGGCGTGTTGGCGGAGAATGGTTTTTCAGGA

GTGGAAACCCTGCCGGATTTGGCGGGTTTGGACAGGGTTACGCTGGGGAAGTATATGAAG

CATTTGAAATAA

The NMB2065 protein sequence

MQEQNRKPSFPIVMLLVSVALWIASLSNVAFYLGNHGSMEGLTVLILGSIFASLDIRYCA

VYANYVWLAAIVLLALRKKVVPVHAALWGLALVAFSVKAVYVDEAGNTSDIVRYGAGFYL

WYAAFAVATIGTFAGKNKERKAASAADGIKMTFDKWLGLSKLPKNEARMLLQYVSEYTRV

QLLTRGGEEMPDEVRQRADRLAQRRLNGEPVAYILGVREFYGRRFTVNPSVLI?PRPETEH

LVEAVLARLPENGRVWDLGTGSGAVAVTVALERPDAFVRASDISPPALETARKNAADLGA

RVEFAHGSWFDTDMPSEGKWDIIVSNPPYIENGDKHLLQGDLRFEPQIALTDFSDGLSCI

RTLAQGAPDRLAEGGFLLLEHGFDQGAAVRGVLAENGFSGVETLPDLAGLDRVTLGKYMK

HLK

The mutant of selecting by vaccination person 17D serum (only screening once)

The NMB0339 DNA sequence

ATGGACAACGAATTGTGGATTATCCTGCTGCCGATTATCCTTTTGCCCGTCTTCTTCGCG

ATGGGCTGGTTTGCCGCCCGCGTGGATATGAAAACCGTATTGAAGCAGGCAAAAAGCATC

CCTTCGGGATTTTATAAAAGCTTGGACGCTTTGGTCGACCGCAACAGCGGGCGCGCGGCA

AGGGAGTTGGCGGAAGTCGTCGACGGCCGGCCGCAATCGTATGATTTGAACCTCACCCTC

GGCAAACTTTACCGCCAGCGTGGCGAAAACGACAAAGCCATCAACATACACCGGACAATG

CTCGATTCTCCCGATACGGTCGGCGAAAAGCGCGCGCGCGTCCTGTTTGAATTGGCGCAA

AACTACCAAAGTGCGGGGTTGGTCGATCGTGCCGAACAGATTTTTTTGGGGCTGCAAGAC

GGTAAAATGGCGCGTGAAGCCAGACAGCACCTGCTCAATATCTACCAACAGGACAGGGAT

TGGGAAAAAGCGGTTGAAACCGCCCGGCTGCTCAGCCATGACGATCAGACCTATCAGTTT

GAAATCGCCCAGTTTTATTGCGAACTTGCCCAAGCCGCGCTGTTCAAGTCCAATTTCGAT

GTCGCGCGTTTCAATGTCGGCAAGGCACTCGAAGCCAACAAAAAATGCACCCGCGCCAAC

ATGATTTTGGGCGACATCGAACACCGACAAGGCAATTTCCCTGCCGCCGTCGAAGCCTAT

GCCGCCATCGAGCAGCAAAACCATGCATACTTGAGCATGGTCGGCGAGAAGCTTTACGAA

GCCTATGCCGCGCAGGGAAAACCTGAAGAAGGCTTGAACCGTCTGACAGGATATATGCAG

ACGTTTCCCGAACTTGACCTGATCAATGTCGTGTACGAGAAATCCCTGCTGCTTAAGTGC

GAGAAAGAAGCCGCGCAAACCGCCGTCGAGCTTGTCCGCCGCAAGCCCGACCTTAACGGC

GTGTACCGCCTGCTCGGTTTGAAACTCAGCGATATGAATCCGGCTTGGAAAGCCGATGCC

GACATGATGCGTTCGGTTATCGGACGGCAGCTACAGCGCAGCGTGATGTACCGTTGCCGC

AACTGCCACTTCAAATCCCAAGTCTTTTTCTGGCACTGCCCCGCCTGCAACAAATGGCAG

ACGTTTACCCCGAATAAAATCGAAGTTTAA

The NMB0339 protein sequence

MDNELWIILLPIILLPVFFAMGWFAARVDMKTVLKQAKSIPSGFYKSLDALVDRNSGRAA

RELAEVVDGRPQSYDLNLTLGKLYRQRGENDKAINIHRTMLDSPDTVGEKRARVLFELAQ

NYQSAGLVDRAEQIFLGLQDGKMAREARQHLLNIYQQDRDWEKAVETARLLSHDDQTYQF

EIAQFYCELAQAALFKSNFDVARFNVGKALEANKKCTRANMILGDIEHRQGNFPAAVEAY

AAIEQQNHAYLSMVGEKLYEAYAAQGKPEEGLNRLTGYMQTFPELDLINVVYEKSLLLKC

EKEAAQTAVELVRRKPDLNGVYRLLGLKLSDMNPAWKADADMMRSVIGRQLQRSVMYRCR

NCHFKSQVFFWHCPACNKWQTFTPNKIEV

The selection of using the patients serum to carry out

We have the gleanings of acute stage and convalescent serum to be used for screening for us.This has come self-infection individuality of the different sero-groups of Neisseria meningitidis.The screening with acute stage (A) or convalescent period (C) serum carry out.Actute infection and to collect period between the serum be 2 thoughtful 3 months.

NMB0401 putA DNA sequence

ATGTTTCATTTTGCATTTCCGGCACAAACTGCCCTGCGCCAAGCGATAACCGATGCCTAC

CGCCGTAATGAAATCGAAGCCGTACAGGATATGTTGCAACGTGCACAGATGAGCGACGAA

GAGCGCAACGCCGCCTCCGAGCTTGCCCGCCGTTTGGTTACCCAAGTCCGCGCCGGCCGC

ACCAAAGCCGGCGGCGTGGATGCGCTGATGCACGAGTTTTCACTCTCCAGCGAAGAAGGC

ATCGCGCTGATGTGTCTGGCAGAAGCCCTGCTGCGTATCCCCGACAACGCCACGCGCGAC

CGCCTGATTGCCGACAAGATTTCAGACGGCAACTGGAAAAGCCATTTGAACAACAGCCCT

TCCCTCTTCGTCAATGCTGCCGCCTGGGGCCTGCTGATTACCGGCAAACTGACCGCCACA

AACGACAAACAAATGAGTTCCGCACTCAGCCGCCTGATCAGCAAAGGCGGCGCACCGCTC

ATCCGCCAAGGCGTAAATTACGCCATGCGGCTTCTGGGCAAACAGTTCGTAACCGGACAG

ACCATTGAAGAAGCCCTGCAAAACGGCAAAGAACGCGAAAAAATGGGCTACCGCTTCTCC

TTCGATATGTTGGGCGAAGCCGCCTACACCCAAGCCGATGCCGACCGCTACTACCGCGAC

TATGTCGAAGCCATCCACGCCATCGGCAAAGATGCGGCAGGACAAGGCGTTTACGAAGGT

AACGGTATTTCCGTCAAACTTTCCGCCATCCATCCGCGCTACTCGCGCACCCAACACGGC

CGCGTGATGGGCGAACTGTTGCCGCGCCTGAAAGAGCTGTTCCTTTTGGGTAAAAAATAC

GATATCGGTATCAACATCGATGCCGAAGAAGCCAACCGTCTGGAGCTGTCTTTGGATTTG

ATGGAGGCTTTGGTTTCAGACCCTGACTTGGCTGGCTACAAAGGTATCGGTTTCGTTGTC

CAAGCCTACCAAAAACGTTGTCCGTTCGTTATCGACTACCTGATCGACCTTGCCCGCCGC

AACAACCAAAAACTAATGATCCGCCTCGTCAAAGGCGCGTATTGGGACAGCGAAATCAAA

TGGGCGCAAGTGGACGGCTTGAACGGCTATCCGACCTACACCCGCAAAGTCCACACCGAC

ATCTCCTACCTCGCCTGCGCGCGCAAACTGCTTTCCGCGCAAGACGCGGTATTCCCGCAA

TTTGCCACCCACAACGCCTACACTTTGGGCGCAATCTACCAAATGGGTAAAGGCAAAGAT

TTTGAACACCAATGCCTGCACGGTATGGGCGAAACCCTGTACGACCAAGTCGTCGGCCCG

CAAAACTTAGGCCGCCGCGTGCGCGTGTACGCCCCAGTCGGCACACACGAAACCCTGCTC

GCCTACTTGGTGCGCCGCCTGTTGGAAAACGGCGCGAACTCGTCTTTCGTCAACCAAATC

GTCGATGAAAACATCAGCATCGACACGCTCATCCGCAGCCCGTTCGACACCATCGCCGAA

CAAGGCATCCACCTGCACAACGCCCTGCCGCTGCCGCGCGATTTGTACGGCAAATGCCGT

CTGAACTCGCAAGGCGTGGACTTGAGCAACGAAAACGTATTGCAGCAGCTTCAAGAACAG

ATGAACAAAGCCGCCGCGCAAGACTTCCACGCCGCATCCATCGTCAACGGCAAAGCCCGC

GATGTCGGCGAAGCGCAACCGATTAAAAACCCTGCCGACCACGACGACATCGTCGGCACA

GTCAGCTTTGCCGATGCCGCGCTTGCCCAAGAAGCGGTTGGCGCAGCCGTTGCCGCGTTC

CCCGAATGGAGTGCGACACCTGCCGCCGAACGCGCCGCCTGCCTGCGCCGTTTTGCCGAT

TTGCTGGAGCAGCACACCCCAGCACTGATGATGCTTGCCGTGCGCGAAGCAGGCAAAACG

CTGAACAACGCCATTGCCGAAGTGCGCGAAGCCGTCGATTTCTGCCGCTACTACGCAAAC

GAAGCCGAACATACCCTGCCTCAAGACGCAAAAGCCGTCGGCGCGATTGTCGCCATCAGC

CCGTGGAACTTCCCGCTCGCCATCTTTACCGGCGAAGTCGTTTCCGCATTGGCGGCAGGC

AACACCGTCATCGCCAAACCCGCCGAACAAACCAGCCTGATTGCCGGTTATGCCGTTTCC

CTCATGCACGAAGCCGGCATCCCGACTTCCGCCCTGCAACTCGTCCTCGGCGCAGGCGAC

GTGGGTGCGGCATTGACCAACGATGCCCGCATCGGCGGCGTGATTTTCACCGGCTCGACC

GAAGTGGCGCGCCTGATCAACAAAGCCCTTGCCAAACGCGGCGACAATCCCGTCCTGATT

GCCGAAACCGGCGGACAAAACGCCATGATTGTCGATTCCACCGCACTTGCCGAGCAAGTC

TGCGCCGACGTATTGAACTCCGCCTTCGACAGCGCGGGACAACGCTGCTCCGCCCTGCGC

ATTTTGTGCGTCCAAGAAGACGTTGCCGACCGTATGCTCGACATGATCAAAGGCGCTATG

GACGAACTCGTCGTCGGCAAACCGATTCAGCTCACTACCGATGTCGGCCCCGTCATCGAT

GCCGAAGCACAGCAAAACCTGTTGAACCACATCAACAAAATGAAAGGTGTTGCCAAGTCC

TACCACGAAGTCAAAACCGCCGCCGATGTCGATTCCAAAAAATCCACGTTCGTTCGCCCC

ATCCTGTTTGAATTGAACAACCTCAACGAACTGCAACGCGAAGTCTTCGGTCCCGTCCTG

CACGTCGTCCGCTACCGCGCCGACGAACTCGACAACGTCATCGACCAAATCAACAGCAAA

GGCTACGCCCTGACCCACGGCGTACACAGCCGCATCGAAGGCACGGTACGCCACATCCGC

AGCCGCATCGAAGCCGGCAACGTTTACGTCAACCGCAACATCGTCGGCGCAGTCGTCGGC

GTACAGCCCTTCGGCGGACACGGTCTGTCCGGCACAGGCCCCAAAGCAGGCGGTTCGTTC

TACCTGCAAAAACTGACCCGCGCCGGCGAATGGGTTGCCCCGACCCTGAGCCAAATCGGA

CAGGCGGACGAAGCCGCACTCAAACGCCTCGAAGCACTGGTTCACAAACTACCGTTCAAC

GCCGAAGAGAAAAAAGCCGCAGCGGCCGCTTTGGGACACGCCCGCATCCGCACCCTGCGC

CGTGCCGAAACCGTCCTTACCGGACCGACCGGCGAGCGCAACAGCATCTCATGGCACGCG

CCCAAACGCGTTTGGATACACGGCGGCAGCACGGTTCAAGCCTTTGCCGCACTGACCGAA

CTTGCCGCCTCCGGCATACAGGCAGTGGTCGAACCCGACAGCCCCTTGGCTTCCTACACT

GCCGACTTGGAAGGTCTGCTGCTGGTCAACGGCAAACCCGAAACCGCCGGCATCAGCCAC

GTTGCCGCCCTGTCGCCTTTGGACAGCGCGCGCAAACAGGAACTTGCCGCCCACGACGGC

GCACTCATCCGCATCCTCCCTTCGGAAAACGGACTCGACATCCTGCAAGTGTTTGAAGAA

ATCTCTTGCAGCGTCAACACCACAGCCGCCGGCGGCAACGCCAGCCTGATGGCGGTCGCC

GACTGA

The NMB0401 protein sequence

MFHFAFPAQTALRQAITDAYRRNEIEAVQDMLQRAQMSDEERNAASELARRLVTQVRAGR

TKAGGVDALMHEFSLSSEEGIALMCLAEALLRIPDNATRDRLIADKISDGNWKSHLNNSP

SLFVNAAAWGLLITGKLTATNDKQMSSALSRLISKGGAPLIRQGVNYAMRLLGKQFVTGQ

TIEEALQNGKEREKMGYRFSFDMLGEAAYTQADADRYYRDYVEAIHAIGKDAAGQGVYEG

NGISVKLSAIHPRYSRTQHGRVMGELLPRLKELFLLGKKYDIGINIDAEEANRLELSLDL

MEALVSDPDLAGYKGIGFVVQAYQKRCPFVIDYLIDLARRNNQKLMIRLVKGAYWDSEIK

WAQVDGLNGYPTYTRKVHTDISYLACARKLLSAQDAVFPQFATHNAYTLGAIYQMGKGKD

FEHQCLHGMGETLYDQVVGPQNLGRRVRVYAPVGTHETLLAYLVRRLLENGANSSFVNQI

VDENISIDTLIRSPFDTIAEQGIHLHNALPLPRDLYGKCRLNSQGVDLSNENVLQQLQEQ

MNKAAAQDFHAASIVNGKARDVGEAQPIKNPADHDDIVGTVSFADAALAQEAVGAAVAAF

PEWSAT?PAAERAACLRRFADLLEQHT?PALMMLAVREAGKTLNNAIAEVREAVDFCRYYAN

EAEHTLPQDAKAVGAIVAISPWNFPLAIFTGEVVSALAAGNTVIAKPAEQTSLIAGYAVS

LMHEAGIPTSALQLVLGAGDVGAALTNDARIGGVIFTGSTEVARLINKALAKRGDNPVLI

AETGGQNAMIVDSTALAEQVCADVLNSAFDSAGQRCSALRILCVQEDVADRMLDMIKGAM

DELVVGKPIQLTTDVGPVIDAEAQQNLLNHINKMKGVAKSYHEVKTAADVDSKKSTFVRP

ILFELNNLNELQREVFGPVLHVVRYRADELDNVIDQINSKGYALTHGVHSRIEGTVRHIR

SRIEAGNVYVNRNIVGAVVGVQPFGGHGLSGTGPKAGGSFYLQKLTRAGEWVAPTLSQIG

QADEAALKRLEALVHKLPFNAEEKKAAAAALGHARIRTLRRAETVLTGPTGERNSISWHA

PKRVWIHGGSTVQAFAALTELAASGIQAVVEPDSPLASYTADLEGLLLVNGKPETAGISH

VAALSPLDSARKQELAAHDGALIRILPSENGLDILQVFEEISCSVNTTAAGGNASLMAVA

D

NMB1335?CreA

DNA and protein sequence have above been provided

NMB1467 PPX DNA sequence

ATGACCACCACCCCCGCAAACGTCCTCGCCTCCGTCGATTTGGGTTCCAACAGTTTCCGC

CTCCAGATTTGCGAAAACAACAACGGACAATTAAAAGTCATCGATTCGTTCAAACAGATG

GTGCGCTTCGCCGCCGGACTGGACGAACAGAAAAATCTGAGTGCCGCTTCCCAAGAACAG

GCTTTGGACTGTCTGGCAAAATTCGGCGAACGCCTGCGCGGCTTCCGCCCTGAACAGGTA

CGCGCCGTGGCAACCAACACATTCCGCGTTGCCAAAAACATCGCAGATTTCCTTCCCAAA

GCCGAAGCGGCATTGGGTTTCCCCATCGAAATCATCGCCGGGCGCGAAGAGGCGCGGCTG

ATTTATACCGGCGTGATCCACACCCTCCCCCCGGGCGGCGGCAAAATGCTGGTTATCGAC

ATCGGCGGCGGTTCGACAGAATTTGTCATCGGCTCGACGCTGAATCCCGACATTACCGAA

AGCCTGCCCTTGGGCTGCGTAACCTACAGCCTGCGCTTCTTCCAAAACAAAATCACCGCC

AAAGACTTCCAATCTGCCATTTCCGCCGCCCGCAACGAAATCCAGCGTATCAGCAAAAAT

ATGAGGCGCGAAGGTTGGGATTTCGCCGTCGGCACATCGGGTTCGGCAAAATCCATCCGC

GACGTGCTTGCCGCCGAAATGCCCCAAGAGGCGGACATTACCTACAAAGGCATGCGCGCC

CTCGCCGAACGCATCATCGAAGCCGGTTCGGTCAAAAAAGCCAAATTTGAAAACCTGAAA

CCGGAACGCATCGAAGTTTTTGCCGGCGGACTTGCCGTGATGATGGCGGCGTTTGAGGAA

ATGAAACTCGACAGGATGACCGTAACCGAAGCCGCCCTGCGCGACGGCGTGTTTTACGAT

TTGATCGGGCGCGGTTTAAACGAAGATATGCGCGGACAAACGGTTGCCGAGTTCCAACAC

CGCTACCACGTCAGCCTCAATCAGGCGAAACGCACCGCCGAGACCGCGCAAACCTTTATG

GACAGCCTCTGCCACGCTAAAAACGTTACAGTTCAAGAGCTTGCCTTGTGGCAACAGTAT

CTCGGACGCGCCGCCGCGCTGCACGAAATCGGTTTGGACATCGCCCACACCGGCTATCAC

AAGCATTCCGCCTACATCCTCGAAAACGCCGATATGCCGGGTTTCTCACGCAAAGAACAG

ACCATACTTGCCCAACTGGTCATCGGTCATCGCGGCGATATGAAAAAAATGAGCGGCATC

ATCGGCACCAACGAAATGTTGTGGTATGCCGTTTTGTCCCTGCGCCTTGCCGCACTGTTC

TGCCGTTCGCGCCAAGACCTGTCTTTCCCGAAAAATATGCAGTTGCGCACGGATACGGAA

AGCTGCGGCTTCATCCTGCGTATTGACAGGGAATGGCTGGAACGCCATCCCCTGATTGCC

GACGCATTGGAATATGAAAGCGTCCAATGGCAAAAAATCAATATGCCGTTCAAAGTCGAG

GCCGTCTGA

The NMB1467 protein sequence

MTTTPANVLASVDLGSNSFRLQICENNNGQLKVIDSFKQMVRFAAGLDEQKNLSAASQEQ

ALDCLAKFGERLRGFRPEQVRAVATNTFRVAKNIADFLPKAEAALGFPIEIIAGREEARL

IYTGVIHTLPPGGGKMLVIDIGGGSTEFVIGSTLNPDITESLPLGCVTYSLRFFQNKITA

KDFQSAISAARNEIQRISKNMRREGWDFAVGTSGSAKSIRDVLAAEMPQEADITYKGMRA

LAERIIEAGSVKKAKFENLKPERIEVFAGGLAVMMAAFEEMKLDRMTVTEAALRDGVFYD

LIGRGLNEDMRGQTVAEFQHRYHVSLNQAKRTAETAQTFMDSLCHAKNVTVQELALWQQY

LGRAAALHEIGLDIAHTGYHKHSAYILENADMPGFSRKEQTILAQLVIGHRGDMKKMSGI

IGTNEMLWYAVLSLRLAALFCRSRQDLSFPKNMQLRTDTESCGFILRIDREWLERHPLIA

DALEYESVQWQKINMPFKVEAV

NMB2056?HemK

ATGAACGGTAAATACTACTACGGCACAGGCCGCCGCAAAAGTTCAGTGGCTCGTGTATTC

CTGATTAAAGGTACAGGTCAAATCATCGTAAACGGTCGTCCCGTTGACGAATTCTTCGCA

CGGGAAACCAGCCGAATGGTTGTTCGCCAACCCTTGGTTCTGACTGAAAACGCCGAATCT

TTCGACATCAAAGTCAATGTTGTTGGCGGCGGCGAAACCGGCCAGTCCGGCGCAATCCGC

CACGGCATTACCCGTGCCCTGATCGACTTCGATGCCGCGTTGAAACCCGCCTTGTCTCAA

GCTGGTTTTGTTACCCGCGATGCCCGCGAAGTCGAACGTAAAAAACCGGGTCTGCGCAAA

GCACGCCGTGCAAAACAATTCTCCAAACGTTAA

The NMB2056 protein sequence

MNGKYYYGTGRRKSSVARVFLIKGTGQIIVNGRPVDEFFARETSRMVVRQPLVLTENAES

FDIKVNVVGGGETGQSGAIRHGITRALIDFDAALKPALSQAGFVTRDAREVERKKPGLRK

ARRAKQFSKR

The NMB0808 DNA sequence

ATGTCCGCCCTCCTCCCCATCATCAACCGCCTGATTCTGCAAAGCCCGGACAGCCGCTCG

GAACTTGCCGCCTTTGCAGGCAAAACACTGACCCTGAACATTGCCGGGCTGAAACTGGCG

GGACGCATCACGGAAGACGGTTTGCTCTCGGCGGGAAACGGCTTTGCAGACACCGAAATT

ACCTTCCGCAACAGCGCGGTACAGAAAATCCTCCAAGGAGGCGAACCCGGGGCGGGCGAC

ATCGGGCTCGAAGGCGACCTCATCCTCGGCATCGCGGTACTGTCCCTGCTCGGCAGCCTG

CGTTCCCGCGCATCGGACGAATTGGCACGGATTTTCGGCACGCAGGCAGACATCGGCAGC

CGTGCCGCCGACATCGGACACGGCATCAAACAAATCGGCAGGAACATCGCCGAACAAATC

GGCGGATTTTCCCGCGAATCCGAGTCCGCAAACATCGGCAACGAAGCCCTTGCCGACTGC

CTCGACGAAATAAGCAGACTGCGCGACGGCGTGGAACGCCTCAACGAACGCCTCGACCGG

CTCGAACGCGACATTTGGATAGACTAA

The NMB0808 protein sequence

MSALLPIINRLILQSPDSRSELAAFAGKTLTLNIAGLKLAGRITEDGLLSAGNGFADTEI

TFRNSAVQKILQGGEPGAGDIGLEGDLILGIAVLSLLGSLRSRASDELARIFGTQADIGS

RAADIGHGIKQIGRNIAEQIGGFSRESESANIGNEALADCLDEISRLRDGVERLNERLDR

LERDIWID

NMB0774 upp DNA sequence

ATGAACGTTAATGTTATCAACCATCCGCTCGTCCGCCACAAATTAACCCTGATGAGGGAG

GCGGATTGCAGCACCTACAAATTCCGGACGCTTGCCACCGAGCTGGCGCGCCTGATGGCA

TACGAGGCAAGCCGTGATTTTGAAATCGAAAAATACCTTATCGACGGATGGTGCGGTCAG

ATTGAAGGCGACCGCATCAAGGGCAAAACATTGACCGTCGTTCCCATACTGCGTGCAGGT

TTGGGTATGCTTGACGGTGTGCTCGACCTGATTCCGACTGCCAAAATCAGTGTAGTCGGA

CTGCAGCGCGACGAAGAAACGCTGAAGCCTATTTCCTATTTTGAGAAATTTGTGGACAGT

ATGGACGAACGTCCGGCTTTGATTATCGATCCTATGCTGGCGACAGGCGGTTCGATGGTT

GCCACCATCGACCTTTTGAAAGCCAAGGGCTGCAAAAATATCAAGGCACTGGTGCTGGTT

GCCGCGCCCGAGGGTGTGAAGGCGGTCAACGACGCGCACCCTGACGTTACGATTTACACC

GCCGCGCTCGACAGCCACTTGAACGAGAACGGCTACATCATCCCCGGCTTGGGCGATGCG

GGCGACAAGATTTTCGGCACGCGCTAA

The NMB0774 protein sequence

MNVNVINHPLVRHKLTLMREADCSTYKFRTLATELARLMAYEASRDFEIEKYLIDGWCGQ

IEGDRIKGKTLTVVPILRAGLGMLDGVLDLIPTAKISVVGLQRDEETLKPISYFEKFVDS

MDERPALIIDPMLATGGSMVATIDLLKAKGCKNIKALVLVAAPEGVKAVNDAHPDVTIYT

AALDSHLNENGYIIPGLGDAGDKIFGTR

The conformity membrane protein D NA sequence that NMA0078 infers

TTGGCGTTTACTTTAATGCGTCGCGCCATGATACGTAAAATGCCCTATACGGAAGATATG

CGCCCAGGCGATACCGCTAATCCTTATGGTGCGTCCAAAGCGATGGTGGAACGGATGTTA

ACCGACATCCAAAAAGCCGATCCGCGCTGGAGCATGATTTTGTTGCGTTATTTCAATCCG

ATTGGCGCGCATGAAAGCGGCTTGATTGGCGAGCAGCCAAACGGCATCCCGAATAATTTG

TTGCCTTATATCTGCCAAGTGGCGGCAGGCAAACTGCCGCAATTGGCGGTATTTGGCGAT

GACTACCCTACCCCCGACGGCACGGGGATGCGTGACTATATTCATGTGATGGATTTGGCA

GAAGGCCATGTCGCGGCTATGCAGGCAAAAAGTAATGTAGCAGGCACGCATTTGCTGAAC

TTAGGCTCCGGCCGCGCTTCTTCGGTGTTGGAAATCATCCGCGCATTTGAAGCAGCTTCG

GGTTTGACGATTCCGTATGAAGTCAAACCGCGCCGTGCCGGTGATTTGGCGTGCTTCTAT

GCCGACCCTTCCTATACAAAGGCGCAAATCGGCTGGCAAACCCAGCGTGATTTAACCCAA

ATGATGGAAGACTCATGGCGCTGGGTGAGTAATAATCCGAATGGCTACGACGATTAA

The NMA0078 protein sequence

MAFTLMRRAMIRKMPYTEDMRPGDTANPYGASKAMVERMLTDIQKADPRWSMILLRYFNP

IGAHESGLIGEQPNGIPNNLLPYICQVAAGKLPQLAVFGDDYPTPDGTGMRDYIHVMDLA

EGHVAAMQAKSNVAGTHLLNLGSGRASSVLEIIRAFEAASGLTIPYEVKPRRAGDLACFY

ADPSYTKAQIGWQTQRDLTQMMEDSWRWVSNNPNGYDD

NMB0337 branched-chain-amino-acid aminotransferase DNA sequence

ATGAGCAGACCCGTACCCGCCGTATTCGGCAGCGTTTTTCACAGTCAAATGCCCGTCCTC

GCCTACCGCGAAGGCAAATGGCAGCCGACCGAATGGCAATCTTCCCAAGACCTCTCCCTC

GCACCGGGCGCGCACGCCCTGCACTACGGCAGCGAATGTTTCGAGGGACTGAAAGCCTTC

CGTCAGGCAGACGGCAAAATCGTGCTGTTCCGTCCGACTGCCAATATCGCGCGTATGCGG

CAAAGTGCGGACATTTTGCACCTGCCGCGCCCCGAAACCGAAGCTTATCTTGACGCGCTA

ATCAAATTGGTCAAACGTGCCGCCGATGAAATTCCCGATGCGCCTGCCGCCCTGTACCTG

CGTCCGACCTTAATCGGTACCGATCCCGTTATCGGCAAGGCCGGTTCTCCTTCCGAAACC

GCCCTGCTGTATATTTTGGCTTCCCCCGTCGGCGACTATTTCAAAGTCGGATCGCCCGTC

AAAATTTTGGTGGAAACCGAACACATCCGCTGCGCCCCGCATATGGGCCGCGTCAAATGC

GGCGGCAACTACGCTTCCGCCATGCACTGGGTGCTGAAGGCGAAAGCCGAATATGGCGCA

AATCAAGTCCTGTTCTGCCCGAACGGCGACGTGCAGGAAACCGGCGCGTCCAACTTTATC

CTGATTAACGGCGATGAAATCATTACCAAACCGCTGACCGACGAGTTTTTGCACGGCGTA

ACCCGCGATTCCGTACTGACGGTTGCCAAAGATTTGGGCTATACCGTCAGCGAACGCAAT

TTCACGGTTGACGAACTCAAAGCTGCGGTGGAAAACGGTGCGGAAGCCATTTTGACCGGT

ACGGCAGCCGTCATCTCGCCCGTTACTTCCTTCGTCATCGGCGGCAAAGAAATCGAAGTG

AAAAGCCAAGAACGCGGCTATGCCATCCGTAAGGCGATTACCGACATCCAGTATGGTTTG

GCGGAAGACAAATACGGCTGGCTGGTTGAAGTGTGCTGA

The NMB0337 protein sequence

MSRPVPAVFGSVFHSQMPVLAYREGKWQPTEWQSSQDLSLAPGAHALHYGSECFEGLKAF

RQADGKIVLFRPTANIARMRQSADILHLPRPETEAYLDALIKLVKRAADEIPDAPAALYL

RPTLIGTDPVIGKAGSPSETALLYILASPVGDYFKVGSPVKILVETEHIRCAPHMGRVKC

GGNYASAMHWVLKAKAEYGANQVLFCPNGDVQETGASNFILINGDEIITKPLTDEFLHGV

TRDSVLTVAKDLGYTVSERNFTVDELKAAVENGAEAILTGTAAVISPVTSFVIGGKEIEV

KSQERGYAIRKAITDIQYGLAEDKYGWLVEVC

NMB0191 ParA family protein DNA sequence

ATGAGTGCGAACATCCTTGCCATCGCCAATCAGAAGGGCGGTGTGGGCAAAACGACGACG

ACGGTAAATTTGGCGGCTTCGCTGGCATCGCGCGGCAAACGCGTGCTGGTGGTCGATTTG

GATCCGCAGGGCAATGCGACGACGGGCAGCGGCATCGACAAGGCGGGTTTGCAGTCCGGC

GTTTATCAGGTCTTATTGGGCGATGCGGACGTGCAGTCGGCGGCGGTACGCAGCAAAGAG

GGCGGATACGCTGTGTTGGGTGCGAACCGCGCGCTGGCCGGCGCGGAAATCGAACTGGTG

CAGGAAATCGCCCGGGAAGTGCGTTTGAAAAACGCGCTCAAGGCAGTGGAAGAAGATTAC

GACTTTATCCTGATCGACTGCCCGCCTTCGCTGACGCTGTTGACGCTTAACGGGCTGGTG

GCGGCGGGCGGCGTGATTGTGCCGATGTTGTGCGAATATTACGCGCTGGAAGGGATTTCC

GATTTGATTGCGACCGTGCGCAAAATCCGTCAGGCGGTCAATCCCGATTTGGACATCACG

GGCATCGTGCGCACGATGTACGACAGCCGCAGCAGGCTGGTTGCCGAAGTCAGCGAACAG

TTGCGCAGCCATTTCGGGGATTTGCTTTTTGAAACCGTCATCCCGCGCAATATCCGCCTT

GCGGAAGCGCCGAGCCACGGTATGCCGGTGATGGCTTACGACGCGCAGGCAAAGGGTACC

AAGGCGTATCTTGCCTTGGCGGACGAGCTGGCGGCGAGGGTGTCGGGGAAATAG

The NMB0191 protein sequence

MSANILAIANQKGGVGKTTTTVNLAASLASRGKRVLVVDLDPQGNATTGSGIDKAGLQSG

VYQVLLGDADVQSAAVRSKEGGYAVLGANRALAGAEIELVQEIAREVRLKNALKAVEEDY

DFILIDCPPSLTLLTLNGLVAAGGVIVPMLCEYYALEGISDLIATVRKIRQAVNPDLDIT

GIVRTMYDSRSRLVAEVSEQLRSHFGDLLFETVIPRNIRLAEAPSHGMPVMAYDAQAKGT

KAYLALADELAARVS?GK

NMB1710 glutamte dehydrogenase (gdhA) DNA sequence

ATGACTGACCTGAACACCCTGTTTGCCAACCTCAAACAACGCAATCCCAATCAGGAGCCG

TTCCATCAGGCGGTTGAAGAAGTCTTCATGAGTCTCGATCCGTTTTTGGCAAAAAATCCG

AAATACACCCAGCAAAGCCTGCTGGAACGCATCGTCGAACCCGAACGCGTCGTGATGTTC

CGCGTAACCTGGCAGGACGATAAAGGGCAAGTCCAAGTCAACCGGGGCTACCGCGTGCAA

ATGAGTTCCGCCATCGGTCCTTACAAAGGCGGCCTGCGCTTCCATCCGACCGTCGATTTG

GGCGTATTGAAATTCCTCGCTTTTGAACAAGTGTTCAAAAACGCCTTGACCACCCTGCCT

ATGGGCGGCGGCAAAGGCGGTTCCGACTTCGACCCCAAAGGCAAATCCGATGCCGAAGTA

ATGCGCTTCTGCCAAGCCTTTATGACCGAACTCTACCGCCACATCGGCGCGGACACCGAT

GTTCCGGCCGGCGACATCGGCGTAGGCGGGCGCGAAATCGGCTACCTGTTCGGACAATAC

AAAAAAAATCCGCAACGAGTTTTCTTCCGTCCTGACCGGCAAAGGTTTGGAATGGGGCGGC

AGCCTCATCCGTCCCGAAGCGACCGGCTACGGCTGCGTCTATTTCGCCCAAGCGATGCTG

CAAACCCGCAACGATAGTTTTGAAGGCAAACGCGTCCTGATTTCCGGCTCCGGCAATGTG

GCGCAATACGCCGCCGAAAAAGCCATCCAACTGGGTGCGAAAGTACTGACCGTTTCCGAC

TCCAACGGCTTCGTCCTCTTCCCCGACAGCGGTATGACCGAAGCGCAACTCGCCGCCTTG

ATCGAATTGAAAGAAGTCCGCCGCGAACGCGTTGCCACCTACGCCAAAGAGCAAGGTCTG

CAATACTTTGAAAAACAAAAACCGTGGGGCGTCGCCGCCGAAATCGCCCTGCCCTGCGCG

ACCCAGAACGAATTGGACGAAGAAGCCGCCAAAACCCTGTTGGCAAACGGCTGCTACGTC

GTTGCCGAAGGTGCGAATATGCCGTCGACTTTGGGCGCGGTCGAGCAATTTATCAAAGCC

GGCATCCTCTACGCCCCGGGAAAAGCCTCCAATGCCGGCGGCGTGGCAACTTCAGGTTTG

GAAATGAGCCAAAACGCCATCCGCCTGTCTTGGACTCGTGAAGAAGTCGACCAACGCCTG

TTCGGCATCATGCAAAGCATCCACGAATCCTGTCTGAAATACGGCAAAGTCGGCGACACA

GTAAACTACGTCAATGGTGCGAACATTGCCGGTTTCGTCAAAGTTGCCGATGCGATGCTG

GCGCAAGGCTTCTAA

The NMB1710 protein sequence

MTDLNTLFANLKQRNPNQEPFHQAVEEVFMSLDPFLAKNPKYTQQSLLERIVEPERVVMF

RVTWQDDKGQVQVNRGYRVQMSSAIGPYKGGLRFHPTVDLGVLKFLAFEQVFKNALTTLP

MGGGKGGSDFDPKGKSDAEVMRFCQAFMTELYRHIGADTDVPAGDIGVGGREIGYLFGQY

KKIRNEFSSVLTGKGLEWGGSLIRPEATGYGCVYFAQAMLQTRNDSFEGKRVLISGSGNV

AQYAAEKAIQLGAKVLTVSDSNGFVLFPDSGMTEAQLAALIELKEVRRERVATYAKEQGL

QYFEKQKPWGVAAEIALPCATQNELDEEAAKTLLANGCYVVAEGANMPSTLGAVEQFIKA

GILYAPGKASNAGGVATSGLEMSQNAIRLSWTREEVDQRLFGIMQSIHESCLKYGKVGDT

VNYVNGANIAGFVKVADAMLAQGF

NMB0062 Cori ester thymidine acyltransferase (rfbA-1) DNA sequence

ATGAAAGGCATCATACTGGCAGGCGGCAGCGGCACGCGCCTCTACCCCATCACGCGCGGC

GTATCCAAACAGCTCCTGCCCGTGTACGACAAACCGATGATTTATTACCCCTTGTCGGTT

TTGATGCTGGCGGGAATCCGCGATATTTTGGTGATTACCGCGCCTGAAGACAACGCCTCT

TTCAAACGCCTGCTTGGCGACGGCAGCGATTTCGGCATTTCCATCAGTTATGCCGTGCAA

CCCAGTCCGGACGGCTTGGCACAGGCATTTATCATCGGCGAAGAATTTATCGGCAACGAC

AATGTTTGCTTGGTTTTGGGCGACAATATTTTTTACGGTCAGTCGTTTACGCAAACATTG

AAACAGGCGGCAGCGCAAACGCACGGCGCAACCGTGTTTGCTTATCAGGTCAAAAACCCC

GAACGTTTCGGCGTGGTTGAATTTAACGAAAACTTCCGCGCCGTTTCCATCGAAGAAAAA

CCGCAACGGCCCAAATCCGATTGGGCGGTAACCGGCTTGTATTTCTACGACAACCGCGCC

GTCGAGTTCGCCAAACAGCTCAAACCGTCCGCACGCGGCGAATTGGAAATTACCGACCTC

AACCGGATGTATTTGGAAGACGGCTCGCTCTCCGTTCAAATATTGGGACGCGGTTTCGCG

TGGCTGGACACCGGCACCCACGAGAGCCTGCACGAAGCCGCTTCATTCGTCCAAACCGTG

CAAAATATCCAAAACCTGCACATCGCCTGCCTCGAAGAAATCGCTTGGCGCAACGGTTGG

CTTTCCGATGAAAAACTGGAAGAATTGGCGCGCCCGATGGCGAAAAACCAATACGGCCAA

TATTTGCTGCGCCTGTTGAAAAAATAA

The NMB0062 protein sequence

MKGIILAGGSGTRLYPITRGVSKQLLPVYDKPMIYYPLSVLMLAGIRDILVITAPEDNAS

FKRLLGDGSDFGISISYAVQPSPDGLAQAFIIGEEFIGNDNVCLVLGDNIFYGQSFTQTL

KQAAAQTHGATVFAYQVKNPERFGVVEFNENFRAVS?IEEKPQRPKSDWAVTGLYFYDNRA

VEFAKQLKPSARGELEITDLNRMYLEDGSLSVQILGRGFAWLDTGTHESLHEAASFVQTV

QNIQNLHIACLEEIAWRNGWLSDEKLEELARPMAKNQYGQYLLRLLKK

NMB 1583 imidazoles glycerol-3-phosphate dehydratase (hisB) DNA sequence

ATGAATTTGACTAAAACACAACGCCAACTGCACAACTTTCTGACCCTCGCCCAAGAAGCA

GGTTCGCTGTCCAAGCTCGCCAAACTCTGCGGCTACCGTACCCCCGTCGCACTCTACAAA

CTCAAACAACGCCTTGAAAAGCAGGCAGAAGACCCAGATGCACGCGGCATCCGTCCCAGC

CTGATGGCAAAACTCGAAAAACACACCGGCAAACCCAAAGGCTGGCTCGACAGAAAACAC

CGCGAACGCACTGTCCCCGAAACCGCCGCAGAAAGCACCGGAACTGCCGAAACCCAAATT

GCCGAAACCGCATCTGCTGCCGGCTGCCGCAGCGTTACCGTCAACCGCAATACCTGCGAA

ACCCAAATCACCGTCTCCATCAACCTCGACGGCAGCGGCAAAAGCAGGCTGGATACCGGC

GTACCCTTCCTCGAACACATGATCGATCAAATCGCCCGCCACGGCATGATTGACATCGAC

ATCAGCTGCAAAGGCGACCTGCACATCGACGACCACCACACCGCCGAAGACATCGGCATC

ACACTCGGACAAGCAATCCGGCAGGCACTCGGCGACAAAAAAGGCATCCGCCGTTACGGA

CATTCCTACGTCCCGCTCGACGAAGCCCTCAGCCGCGTCGTCATCGACCTTTCCGGCCGC

CCCGGACTCGTGTACAACATCGAATTTACCCGCGCACTAATCGGACGTTTCGATGTCGAT

TTGTTTGAAGAATTTTTCCACGGCATCGTCAACCACAGTATGATGACCCTGCACATCGAC

AACCTCAGCGGCAAAAACGCCCACCATCAGGCGGAAACCGTATTCAAAGCCTTCGGGCGC

GCCCTGCGTATGGCAGTCGAACACGACCCGCGCATGGCAGGACAGACCCCCTCGACCAAA

GGCACGCTGACCGCATAA

The NMB1583 protein sequence

MNLTKTQRQLHNFLTLAQEAGSLSKLAKLCGYRTPVALYKLKQRLEKQAEDPDARGIRPS

LMAKLEKHTGKPKGWLDRKHRERTVPETAAESTGTAETQIAETASAAGCRSVTVNRNTCE

TQITVSINLDGSGKSRLDTGVPFLEHMIDQIARHGMIDIDISCKGDLHIDDHHTAEDIGI

TLGQAIRQALGDKKGIRRYGHSYVPLDEALSRVVIDLSGRPGLVYNIEFTRALIGRFDVD

LFEEFFHGIVNHSMMTLHIDNLSGKNAHHQAETVFKAFGRALRMAVEHDPRMAGQTPSTK

GTLTA

Following other antigen uses aforesaid basically method to identify and obtains:

The NMB1333 nucleotide sequence

ATGCGCTACAAACCCCTTCTGCTTGCCCTGATGCTCGTTTTTTCCACGCCCGCCGTTGCC

GCCCACGACGCGGCACACAACCGTTCCGCCGAAGTGAAAAAACAGACGAAGAACAAAAAA

GAACAGCCCGAAGCGGCGGAAGGCAAAAAAGAAAAAGGCAAAAATGGCGCAGTGAAAGAT

AAAAAAACAGGCGGCAAAGAGGCGGCAAAAGAGGGCAAAGAGTCCAAAAAAACCGCCAAA

AACCGCAAAGAAGCAGAGAAGGAGGCGACATCCAGGCAGTCTGCGCGCAAAGGACGCGAA

GGGGATAAGAAATCGAAGGCGGAACACAAAAAGGCACATGGCAAGCCCGTGTCCGGATCC

AAAGAAAAAAACGCAAAAACACAGCCTGAAAACAAACAAGGCAAAAAAGAGGCAAAAGGA

CAGGGCAATCCGCGCAAGGGCGGCAAGGCGGAAAAAGACACTGTTTCTGCAAATAAAAAA

GTCCGTTCCGACAAGAACGGCAAAGCAGTGAAACAGGACAAAAAATACAGGGAAGAGAAA

AATGCCAAAACCGATTCCGACGAATTGAAAGCCGCCGTTGCCGCTGCCACCAATGATGTC

GAAAACAAAAAAGCCCTGCTCAAACAAAGCGAAGGAATGCTGCTTCATGTCAGCAATTCC

CTCAAACAGCTTCAGGAAGAGCGTATCCGCCAAGAGCGTATCCGTCAGGCGCGCGGCAAC

CTTGCTTCCGTCAACCGCAAACAGCGCGAGGCTTGGGACAAGTTCCAAAAACTCAATACC

GAGCTGAACCGTTTGAAAACGGAAGTCGCCGCTACGAAAGCGCAGATTTCCCGTTTCGTA

TCGGGGAACTATAAAAACAGCCAGCCGAATGCGGTTGCCCTGTTCCTGAAAAACGCCGAA

CCGGGTCAGAAAAACCGCTTTTTGCGTTATACGCGTTATGTAAACGCCTCCAATCGGGAA

GTTGTCAAGGATTTGGAAAAACAGCAGAAGGCTTTGGCGGTACAAGAGCAGAAAATCAAC

AATGAGCTTGCCCGTTTGAAGAAAATTCAGGCAAACGTGCAATCTCTGCTGAAAAAACAG

GGTGTAACCGATGCGGCGGAACAGACGGAAAGCCGCAGACAGAATGCCAAAATCGCCAAA

GATGCCCGAAAACTGCTGGAACAGAAAGGGAACGAGCAGCAGCTGAACAAGCTCTTGAGC

AATTTGGAGAAGAAAAAGGCCGAACACCGCATTCAGGATGCGGAAGCAAAAAGAAAATTG

GCTGAAGCCAGACTGGCGGCAGCCGAAAAAGCCAGAAAAGAAGCGGCGCAGCAGAAGGCT

GAAGCACGACGTGCGGAAATGTCCAACCTGACCGCCGAAGACAGGAACATCCAAGCGCCT

TCGGTTATGGGTATCGGCAGTGCCGACGGTTTCAGCCGCATGCAAGGACGTTTGAAAAAA

CCGGTTGACGGTGTGCCGACCGGACTTTTCGGGCAGAACCGGAGCGGCGGCGATATTTGG

AAAGGCGTGTTCTATTCCACTGCACCGGCAACGGTTGAAAGCATTGCGCCGGGAACGGTA

AGCTATGCGGACGAGTTGGACGGCTACGGCAAAGTGGTCGTGGTCGATCACGGCGAGAAC

TACATCAGCATCTATGCCGGTTTGAGCGAAATTTCCGTCGGCAAGGGTTATATGGTCGCG

GCAGGAAGCAAAATCGGCTCGAGCGGGTCGCTGCCGGACGGGGAAGAGGGGCTTTACCTG

CAAATACGTTATCAAGGTCAGGTATTGAACCCTTCGAGCTGGATACGTTGA

The NMB1333 aminoacid sequence

MRYKPLLLALMLVFSTPAVAAHDAAHNRSAEVKKQTKNKKEQPEAAEGKKEKGKNGAVKD

KKTGGKEAAKEGKESKKTAKNRKEAEKEATSRQSARKGREGDKKSKAEHKKAHGKPVSGS

KEKNAKTQPENKQGKKEAKGQGNPRKGGKAEKDTVSANKKVRS?DKNGKAVKQDKKYREEK

NAKTDSDELKAAVAAATNDVENKKALLKQSEGMLLHVSNSLKQLQEERIRQERIRQARGN

LASVNRKQREAWDKFQKLNTELNRLKTEVAATKAQISRFVSGNYKNSQPNAVALFLKNAE

PGQKNRFLRYTRYVNASNREVVKDLEKQQKALAVQEQKINNELARLKKIQANVQSLLKKQ

GVTDAAEQTESRRQNAKIAKDARKLLEQKGNEQQLNKLLSNLEKKKAEHRIQDAEAKRKL

AEARLAAAEKARKEAAQQKAEARRAEMSNLTAEDRNIQAPSVMGIGSADGFSRMQGRLKK

PVDGVPTGLFGQNRSGGDIWKGVFYSTAPATVESIAPGTVSYADELDGYGKVVVVDHGEN

YISIYAGLSEISVGKGYMVAAGSKIGSSGSLPDGEEGLYLQIRYQGQVLNPSSWIR

The NMB0377 nucleotide sequence

ATGGCGTTTTGCACCAGTTTGGGAGTGATGATGGAAACACAGCTTTACATCGGCATCATG

TCGGGAACCAGCATGGACGGGGCGGATGCCGTACTGATACGGATGGACGGCGGCAAATGG

CTGGGCGCGGAAGGGCACGCCTTTACCCCCTACCCCGGCAGGTTACGCCGCCAATTGCTG

GATTTGCAGGACACAGGCGCAGACGAACTGCACCGCAGCAGGATTTTGTCGCAAGAACTC

AGCCGCCTATATGCGCAAACCGCCGCCGAACTGCTGTGCAGTCAAAACCTCGCACCGTCC

GACATTACCGCCCTCGGCTGCCACGGGCAAACCGTCCGACACGCGCCGGAACACGGTTAC

AGCATACAGCTTGCCGATTTGCCGCTGCTGGCGGAACGGACGCGGATTTTTACCGTCGGC

GACTTCCGCAGCCGCGACCTTGCGGCCGGCGGACAAGGCGCGCCACTCGTCCCCGCCTTT

CACGAAGCCCTGTTCCGCGACAACAGGGAAACACGCGCGGTACTGAACATCGGCGGGATT

GCCAACATCAGCGTACTCCCCCCCGACGCACCCGCCTTCGGCTTCGACACAGGGCCGGGC

AATATGCTGATGGACGCGTGGACGCAGGCACACTGGCAGCTTCCTTACGACAAAAACGGT

GCAAAGGCGGCACAAGGCAACATATTGCCGCAACTGCTCGACAGGCTGCTCGCCCACCCG

TATTTCGCACAACCCCACCCTAAAAGCACGGGGCGCGAACTGTTTGCCCTAAATTGGCTC

GAAACCTACCTTGACGGCGGCGAAAACCGATACGACGTATTGCGGACGCTTTCCCGTTTT

ACCGCGCAAACCGTTTGCGACGCCGTCTCACACGCAGCGGCAGATGCCCGTCAAATGTAC

ATTTGCGGCGGCGGCATCCGCAATCCTGTTTTAATGGCGGATTTGGCAGAATGTTTCGGC

ACACGCGTTTCCCTGCACAGCACCGCCGACCTGAACCTCGATCCGCAATGGGTGGAAGCC

GCCGCATTTGCGTGGTTGGCGGCGTGTTGGATTAATCGCATTCCCGGTAGTCCGCACAAA

GCAACCGGCGCATCCAAACCGTGTATTCTGGGCGCGGGATATTATTATTGA

The NMB0377 aminoacid sequence

MAFCTSLGVMMETQLYIGIMSGTSMDGADAVLIRMDGGKWLGAEGHAFTPYPGRLRRQLL

DLQDTGADELHRSRILSQELSRLYAQTAAELLCSQNLAPSDITALGCHGQTVRHAPEHGY

SIQLADLPLLAERTRIFTVGDFRSRDLAAGGQGAPLVPAFHEALFRDNRETRAVLNIGGI

ANISVLPPDAPAFGFDTGPGNMLMDAWTQAHWQLPYDKNGAKAAQGNILPQLLDRLLAHP

YFAQPHPKSTGRELFALNWLETYLDGGENRYDVLRTLSRFTAQTVCDAVSHAAADARQMY

ICGGGIRNPVLMADLAECFGTRVSLHSTADLNLDPQWVEAAAFAWLAACWINRIPGSPHK

ATGASKPCILGAGYYY

The NMB0264 nucleotide sequence

ATGTTGAACAAAATATTTTCCTGGTTCGAGTCCCGAATCGACCCTTATCCCGAAGCCGCC

CCGAAAACGCCAGAAAAAGGCTTGTGGCGGTTTGTCTGGAGCAGCATGGCCGGCGTGCGG

AAATGGATAGCCGCCCTGGCTGCGCTGACCGCCGGCATCGGCATTATGGAAGCCCTGGTT

TTTCAATTTATGGGCAAAATCGTGGAGTGGCTCGGCAAATACGCGCCCGCCGAACTGTTT

GCCGAAAAAAGTTGGGAACTGGCGGCAATGGCGGCGATGATGGTATTTTCGGTTGCGTGG

GCGTTTGCCGCGTCCAACGTGCGCCTGCAAACCCTTCAGGGCGTGTTCCCCATGCGCCTG

CGCTGGAACTTCCACCGCCTGATGCTGAACCAAAGCCTCGGTTTTTATCAGGACGAATTT

GCCGGACGCGTGTCCGCCAAAGTCATGCAGACCGCGCTGGCGTTGCGCGACGCGGTGATG

ACGGTTGCCGATATGGTCGTTTATGTGTCGGTGTATTTCATTACCTCCGGCGTGATTCTC

GCCTCGCTCGACTCATGGCTGCTGCTGCCCTTTATCGGCTGGATTGTCGGTTTCGCTTCG

GTGATGCGCCTGCTGATTCCCAAATTGGGGCAAACCGCCGCATGGCAGGCGGATGCCCGC

TCGCTGATGACCGGCCGCATTACCGATGCCTATTCCAATATCGCCACCGTCAAACTCTTC

TCCCACGGCGCGCGTGAAGCCGCCTATGCCAAGCAGTCGATGGAAGAATTTATGGTTACG

GTGCGCGCCCAAATGCGGCTGGCGACGCTGCTGCATTCGTGCAGCTTCATCGTCAACACC

TCCCTGACCCTCTCCACCGCCGCACTGGGCATCTGGCTCTGGCACAACGGGCAGGTCGGC

GTGGGCGCGGTTGCTACAGCCACCGCCATGGCGTTGCGCGTCAACGGTTTGTCGCAATAC

ATTATGTGGGAATCCGCGCGGCTGTTTGAAAACATCGGCACCGTCGGCGACGGCATGGCA

ACCCTGTCCAAACCGCACACCATCCTCGACAAGCCCCGGGCACTGCCGCTGAACGTGCCG

CAAGGCGCAATCAAATTTGAACACGTCGATTTCTCCTACGAAGCGGGCAAACCGCTGCTC

AACGGCTTCAACCTCACCATCCGCCCGGGCGAAAAAGTCGGCTTGATCGGACGCAGCGGC

GCGGGCAAATCCACCATCGTCAACCTGCTTTTGCGCTTCTACGAACCGCAAAGCGGCACG

GTTTCGATCGACGGGCAGGACATAAGCGGCGTTACCCAAGAATCTTTACGCGCCCAAATC

GGTTTGGTCACGCAAGATACCTCGCTGCTGCACCGTTCCGTGCGCGACAACATTATTTAC

GGCCGCCCCGACGCGACCGATGCCGAAATGGTTTCTGCCGCCGAACGCGCCGAAGCCGCC

GGCTTCATCCCCGACCTTTCCGATGCCAAAGGGCGGCGCGGCTACGACGCACACGTCGGC

GAACGCGGCGTGAAACTCTCCGGCGGGCAACGCCAGCGCATCGCCATCGCCCGCGTGATG

CTCAAAGACGCACCGATTCTTCTTTTGGACGAAGCCACCAGCGCGCTCGATTCCGAAGTC

GAAGCCGCCATCCAAGAAAGCCTCGACAAAATGATGGACGGCAAAACCGTCATCGCCATC

GCCCACCGCCTCTCCACCATCGCCGCAATGGACAGGCTCGTCGTCCTCGACAAAGGCCGC

ATCATCGAAGAAGGCACACACGCCGAACTCCTCGAAAAACGCGGGCTTTACGCCAAACTC

TGGGCGCACCAGAGCGGCGGCTTCCTCAACGAACACGTCGAGTGGCAGCACGACTGA

The NMB0264 aminoacid sequence

MLNKIFSWFESRIDPYPEAAPKTPEKGLWRFVWSSMAGVRKWIAALAALTAGIGIMEALV

FQFMGKIVEWLGKYAPAELFAEKSWELAAMAAMMVFSVAWAFAASNVRLQTLQGVFPMRL

RWNFHRLMLNQSLGFYQDEFAGRVSAKVMQTALALRDAVMTVADMVVYVSVYFITSGVIL

ASLDSWLLLPFIGWIVGFASVMRLLIPKLGQTAAWQADARSLMTGRITDAYSNIATVKLF

SHGAREAAYAKQSMEEFMVTVRAQMRLATLLHSCSFIVNTSLTLSTAALGIWLWHNGQVG

VGAVATATAMALRVNGLSQYIMWESARLFENIGTVGDGMATLSKPHTILDKPRALPLNVP

QGAIKFEHVDFSYEAGKPLLNGFNLTIRPGEKVGLIGRSGAGKSTIVNLLLRFYEPQSGT

VSIDGQDISGVTQESLRAQIGLVTQDTSLLHRSVRDNIIYGRPDATDAEMVSAAERAEAA

GFIPDLSDAKGRRGYDAHVGERGVKLSGGQRQRIAIARVMLKDAPILLLDEATSALDSEV

EAAIQESLDKMMDGKTVIAIAHRLSTIAAMDRLVVLDKGRIIEEGTHAELLEKRGLYAKL

WAHQSGGFLNEHVEWQHD

The NMB1036 nucleotide sequence

ATGACAGCACAAACCCTCTACGACAAACTTTGGAACAGCCACGTCGTCCGCGAAGAAGAA

GACGGCACCGTCCTGCTCTACATCGACCGCCATTTGGTGCACGAAGTTACCAGCCCTCAG

GCATTTGAAGGCTTGAAAATGGCGGGGCGCAAGCTGTGGCGCATCGACAGCGTCGTCTCC

ACCGCCGACCACAACACCCCGACCGGCGATTGGGACAAAGGCATCCAAGACCCGATTTCC

AAGCTGCAAGTCGATACTTTGGACAAAAACATTAAAGAGTTTGGCGCACTCGCCTATTTT

CCGTTTATGGACAAAGGTCAGGGCATCGTACACGTTATGGGCCCCGAACAAGGCGCGACC

CTGCCCGGTATGACCGTCGTCTGCGGCGACTCGCACACTTCCACCCACGGCGCATTCGGC

GCACTGGCGCACGGCATCGGCACTTCCGAAGTCGAGCACACCATGGCGACCCAATGTATT

ACCGCGAAAAAATCCAAATCCATGCTGATTTCCGTTGACGGCAAATTAAAAGCGGGCGTT

ACCGCCAAAGACGTGGCGCTCTACATCATCGGGCAAATCGGCACGGCAGGCGGTACAGGC

TACGCCATCGAGTTTGGCGGCGAAGCCATCCGCAGCCTTTCTATGGAAAGCCGCATGACT

TTATGCAATATGGCGATTGAGGCAGGCGCGCGCTCAGGCATGGTTGCCGTCGACCAAACC

ACCATCGACTACGTAAAAGATAAACCCTTCGCACCCGAAGGCGAAGCGTGGGACAAAGCC

GTCGAGTACTGGCGTACGCTGGTGTCTGACGAAGGTGCGGTATTCGACAAAGAATACCGT

TTCAACGCCGAAGACATCGAACCGCAAGTCACTTGGGGTACCTCGCCTGAAATGGTTTTA

GACATCAGCAGCAAAGTGCCGAATCCTGCCGAAGAAACCGATCCGGTCAAACGCAGCGGT

ATGGAACGCGCCCTTGAATACATGGGCTTGGAAGCCGGTACGCCATTAAACGAAATCCCC

GTCGACATCGTATTCATCGGCTCTTGCACCAACAGCCGCATCGAAGACTTGCGCGAAGCC

GCCGCCATCGCCAAAGACCGCAAAAAAGCCGCCAACGTACAGCGCGTGTTAATCGTCCCC

GGCTCCGGTTTGGTTAAAGAACAAGCCGAAAAAGAAGGCTTGGACAAAATTTTCATCGAA

GCCGGTTTTGAATGGCGCGAACCGGGCTGTTCGATGTGTCTCGCCATGAACGCCGACCGC

CTGACCCCGGGGCAACGCTGCGCCTCCACCTCCAACCGTAACTTTGAAGGCCGTCAAGGC

AACGGCGGACGTACCCACCTCGTCAGCCCCGCTATGGCAGCAGCCGCCGCCGTTACCGGC

CGCTTTACCGACATCCGCATGATGGCGTAA

The NMB1036 aminoacid sequence

MTAQTLYDKLWNSHVVREEEDGTVLLYIDRHLVHEVTSPQAFEGLKMAGRKLWRIDSVVS

TADHNTPTGDWDKGIQDPISKLQVDTLDKNIKEFGALAYFPFMDKGQGIVHVMGPEQGAT

LPGMTVVCGDSHTSTHGAFGALAHGIGTSEVEHTMATQCITAKKSKSMLISVDGKLKAGV

TAKDVALYIIGQIGTAGGTGYAIEFGGEAIRSLSMESRMTLCNMAIEAGARSGMVAVDQT

TIDYVKDKPFAPEGEAWDKAVEYWRTLVSDEGAVFDKEYRFNAEDIEPQVTWGTSPEMVL

DISSKVPNPAEETDPVKRSGMERALEYMGLEAGTPLNEIPVDIVFIGSCTNSRIEDLREA

AAIAKDRKKAANVQRVLIVPGSGLVKEQAEKEGLDKIFIEAGFEWREPGCSMCLAMNADR

LTPGQRCASTSNRNFEGRQGNGGRTHLVSPAMAAAAAVTGRFTDIRMMA

The NMB1176 nucleotide sequence

ATGAAAGACAAGCACGATTCTTCCGCCATGCGGCTGGACAAATGGCTTTGGGCGGCACGT

TTTTTCAAGACCCGTTCCCTTGCGCAAAAGCACATCGAACTGGGTAGGGTTCAAGTAAAC

GGCTCGAAGGTCAAAAACAGTAAAACCATAGACATCGGCGATATTATCGACCTGACGCTC

AATTCCCTTCCCTATAAAATCAAGGTTAAAGGTTTGAACCACCAACGCCGCCCGGCATCC

GAGGCGCGGCTTCTGTATGAAGAGGACGCGAAAACGGCAACATTGAGGGAAGAGCGCAAA

CAGCTCGACCAATTCAGCCGCATCACTTCCGCCTATCCCGACGGCAGACCGACCAAGCGC

GACCGCCGCCAACTGGACAGGCTGAAAAAAGGAGACTGGTAA

The NMB1176 aminoacid sequence

MKDKHDSSAMRLDKWLWAARFFKTRSLAQKHIELGRVQVNGSKVKNSKTIDIGDIIDLTL

NSLPYKIKVKGLNHQRRPASEARLLYEEDAKTATLREERKQLDQFSRITSAYPDGRPTKR

DRRQLDRLKKGDW

The NMB1359 nucleotide sequence

ATGAACCACACCGTTACCCTGCCCGACCAAACCACCTTTGCCGCCAACGACGGCGAAACC

GTTTTGACCGCTGCCGCCCGTCAAAACCTCAACCTGCCCCATTCCTGCAAAAGCGGTGTC

TGCGGACAATGCAAAGCCGAACTGGTCAGCGGCGATATTCAAATGGGCGGACACTCGGAA

CAGGCTTTATCCGAAGCAGAAAAAGCGCAAGGCAAGATTTTGATGTGCTGCACCACTGCG

CAAAGCGATATCAACATCAACATCCCCGGCTACAAAGCCGATGCCCTACCCGTCCGCACC

CTGCCCGCACGCATCGAAAGTATTATTTTCAAACACGATGTCGCCCTCCTGAAACTTGCC

CTGCCCAAAGCCCCGCCGTTTGCCTTCTACGCCGGGCAATACATTGATTTACTGCTGCCG

GGCAACGTCAGCCGCAGCTACTCCATCGCCAATTTACCCGACCAAGAAGGCATTTTGGAA

CTGCACATCCGCAGGCACGAAAACGGTGTCTGCTCGGAAATGATTTTCGGCAGCGAACCC

AAAGTCAAAGAAAAAGGCATCGTCCGCGTTAAAGGCCCGCTCGGTTCGTTTACCTTGCAG

GAAGACAGCGGCAAACCCGTCATCCTGCTGGCAACCGGCACAGGCTACGCCCCCATCCGC

AGCATCCTGCTCGACCTTATCCGCCAAGGCAGCAACCGCGCCGTCCATTTCTACTGGGGC

GCGCGTCATCAGGATGATTTGTATGCCCTCGAAGAAGCACAAGGGTTGGCATGCCGTCTG

AAAAACGCCTGCTTCACCCCCGTATTGTCCCGCCCCGGAGAGGGCTGGCAGGGAAGAAAT

GGTCACGTACAAGACATCGCGGCACAAGACCACCCCGACCTGTCGGAATACGAAGTATTT

GCCTGCGGTTCTCCGGCCATGACCGAACAAACAAAGAATCTGTTTGTGCAACAGCATAAG

CTGCCGGAAAACTTGTTTTTCTCCGACGCATTCACGCCGTCCGCATCATAA

The NMB1359 aminoacid sequence

MNHTVTLPDQTTFAANDGETVLTAAARQNLNLPHSCKSGVCGQCKAELVSGDIQMGGHSE

QALSEAEKAQGKILMCCTTAQSDININIPGYKADALPVRTLPARIESIIFKHDVALLKLA

LPKAPPFAFYAGQYIDLLLPGNVSRSYSIANLPDQEGILELHIRRHENGVCSEMIFGSEP

KVKEKGIVRVKGPLGSFTLQEDSGKPVILLATGTGYAPIRSILLDLIRQGSNRAVHFYWG

ARHQDDLYALEEAQGLACRLKNACFTPVLSRPGEGWQGRNGHVQDIAAQDHPDLSEYEVF

ACGSPAMTEQTKNLFVQQHKLPENLFFSDAFTPSAS

The NMB1138 nucleotide sequence

ATGAAAGACAAGCACGATTCTTCCGCCATGCGGCTGGACAAATGGCTTTGGGCGGCACGT

TTTTTCAAGACCCGTTCCCTTGCGCAAAAGCACATCGAACTGGGTAGGGTTCAAGTAAAC

GGCTCGAAGGTCAAAAACAGTAAAACCATAGACATCGGCGATATTATCGACCTGACGCTC

AATTCCCTTCCCTATAAAATCAAGGTTAAAGGTTTGAACCACCAACGCCGCCCGGCATCC

GAGGCGCGGCTTCTGTATGAAGAGGACGCGAAAACGGCAACATTGAGGGAAGAGCGCAAA

CAGCTCGACCAATTCAGCCGCATCACTTCCGCCTATCCCGACGGCAGACCGACCAAGCGC

GACCGCCGCCAACTGGACAGGCTGAAAAAAGGAGACTGGTAA

The NMB1138 aminoacid sequence

MKDKHDSSAMRLDKWLWAARFFKTRSLAQKHIELGRVQVNGSKVKNSKTIDIGDIIDLTL

NSLPYKIKVKGLNHQRRPASEARLLYEEDAKTATLREERKQLDQFSRITSAYPDGRPTKR

DRRQLDRLKKGDW

Sequence table

Sequence numbering (SEQ ID No) sequence

1 NMB0341?DNA

2 NMB0341 albumen

3 NMB1583?DNA

4 NMB1583 albumen

5 NMB1345?DNA

6 NMB1345 albumen

7 NMB0738?DNA

8 NMB0738 albumen

9 NMB0792?DNA

10 NMB0792 albumen

11 NMB0279?DNA

12 NMB0279 albumen

13 NMB2050?DNA

14 NMB2050 albumen

15 NMB1335?DNA

16 NMB1335 albumen

17 NMB2035?DNA

18 NMB2035 albumen

19 NMB1351?DNA

20 NMB1351 albumen

21 NMB1574?DNA

22 NMB1574 albumen

23 NMB1298?DNA

24 NMB1298 albumen

25 NMB1856?DNA

26 NMB1856 albumen

27 NMB0119?DNA

28 NMB0119 albumen

29 NMB1705?DNA

30 NMB1705 albumen

31 NMB2065?DNA

32 NMB2065 albumen

33 NMB0339?DNA

34 NMB0339 albumen

35 NMB0401?DNA

36 NMB0401 albumen

37 NMB1467?DNA

38 NMB1467 albumen

39 NMB2056?DNA

40 NMB2056 albumen

41 NMB0808?DNA

42 NMB0808 albumen

43 NMB0774?DNA

44 NMB0774 albumen

45 NMA0078?DNA

46 NMA0078 albumen

47 NMB0337?DNA

48 NMB0337 albumen

49 NMB0191?DNA

50 NMB0191 albumen

51 NMB1710?DNA

52 NMB1710 albumen

53 NMB0062?DNA

54 NMB0062 albumen

55 NMB1333?DNA

56 NMB1333 albumen

57 NMB0377?DNA

58 NMB0377 albumen

59 NMB0264?DNA

60 NMB0264 albumen

61 NMB1036?DNA

62 NMB1036 albumen

63 NMB1176?DNA

64 NMB1176 albumen

65 NMB1359?DNA

66 NMB1359 albumen

67 NMB1138?DNA

68 NMB1138 albumen

Claims (9)

1. comprise and be selected from SEQ ID No 2,4,6,8,10,12,14,16, the polypeptide of arbitrary aminoacid sequence in 18,20,22,24,26,28,30,32,34,36,38,40,42,44,46,48,50,52,54,56,58,60,62,64,66,68; Or the fusions of its fragment or variant or this type of fragment or variant.

2. coding is according to the polynucleotide of the polypeptide of claim 1.

3. be used for medicine according to the polypeptide of claim 1 or according to the polynucleotide of claim 2.

4. be used for vaccine according to the polypeptide of claim 1 or according to the polynucleotide of claim 2.

5. be used to prepare the method according to the polypeptide of claim 1, this method is included in to be expressed the polynucleotide of claim 2 and separates described polypeptide in the host cell.

6. be used to prepare method, comprise the described polypeptide of chemosynthesis according to the polypeptide of claim 1.

7. to the method for individual vaccination with the opposing Neisseria meningitidis, this method comprises to be used according to the polypeptide of claim 1 or according to the polynucleotide of claim 2 individuality.

8. according to the polypeptide of claim 1 or according to the purposes of polynucleotide in the preparation vaccine of claim 2, it is individual with the opposing Neisseria meningitidis that this vaccine is used for inoculation.

9. Pharmaceutical composition comprises according to the polypeptide of claim 1 or according to the polynucleotide and the pharmaceutically acceptable carrier of claim 2.