EP1005367A2 - Vaccin contenant un antigene de bordetella pertussis - Google Patents

Vaccin contenant un antigene de bordetella pertussis

Info

Publication number
EP1005367A2
EP1005367A2 EP98930917A EP98930917A EP1005367A2 EP 1005367 A2 EP1005367 A2 EP 1005367A2 EP 98930917 A EP98930917 A EP 98930917A EP 98930917 A EP98930917 A EP 98930917A EP 1005367 A2 EP1005367 A2 EP 1005367A2
Authority
EP
European Patent Office
Prior art keywords
pertussis
conjugate
antigen
fimbria
fimbriae
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP98930917A
Other languages
German (de)
English (en)
Inventor
Graham Henry Farrar
David Hugh Jones
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Health Protection Agency
Original Assignee
Health Protection Agency
Microbiological Research Authority
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Health Protection Agency, Microbiological Research Authority filed Critical Health Protection Agency
Publication of EP1005367A2 publication Critical patent/EP1005367A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/385—Haptens or antigens, bound to carriers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/02—Bacterial antigens
    • A61K39/095—Neisseria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/02—Bacterial antigens
    • A61K39/099—Bordetella
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55505—Inorganic adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
    • A61K2039/6031—Proteins
    • A61K2039/6068—Other bacterial proteins, e.g. OMP
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/70—Multivalent vaccine
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention relates to vaccines containing Bordetella pertussis antigen, to conjugate vaccines, to methods of conjugating carrier and immunising components to form a vaccine conjugate and to use of a conjugate vaccine for vaccination of humans and animals, and also to oral vaccines against pertussis.
  • carbohydrate capsule which is an essential virulence component.
  • the carbohydrate capsules are potential vaccine components since antibodies directed against them are usually protective by virtue of their complement-mediated bactericidal activity.
  • Antibodies raised against the carbohydrate are specific for the particular serogroup from which the carbohydrate was obtained; there is one major pathogenic serogroup for Haemophilus influenzae, four major serogroups for Neisseria meningitidis and over 80 serogroups for a Streptococcus pneumoniae.
  • capsular vaccines are T-cell independent antigens and hence the immune response they raise is low (especially in infants), short-lived, unboostable and has an affinity which does not mature.
  • the antigens can be converted to T-cell dependency by conjugation to proteins which enhance the immune response, including providing a memory response.
  • Hib Haemophilus influenzae type b
  • Another difficulty relates to the practicalities of increasing the number and complexity of vaccines for paediatric immunisation.
  • Vaccine manufacturers have been successful in producing combinations of paediatric vaccines which can be delivered simultaneously from one syringe, thus simplifying immunisation programmes.
  • the prospect of re-introducing multiple injections with all of the corresponding problems of increasingly complex vaccination programmes is likely to occur unless suitable alternative delivery systems (e.g. to mucosal surfaces) are introduced.
  • conjugate vaccine for presentation of an immunogenic carbohydrate in a conjugate which can be used in parallel with or subsequently to existing toxoid based vaccines with amelioration or reduction of the problems and potential problems hitherto encountered.
  • a further object is to provide a carrier protein that is an alternative to the existing toxoid carriers, for manufacture of a conjugate vaccine.
  • a still further object is to provide vaccines that can be used for vaccination against more than one pathogen in a single vaccine formulation.
  • a first aspect of the invention provides a conjugate, for use in a vaccine, comprising an antigen conjugated to a carrier selected from (i) a fimbria of Bordetella pertussis, (ii) a pertussis toxin, (iii) a pertussis toxoid, and (iv) pertussis 69kD protein.
  • the antigen is suitably an antigenic component of a pathogenic bacteria or virus, in which context "antigen" is to be understood to encompass variants, derivatives and fragments of an antigenic component of a pathogenic bacteria or virus such that immunisation with the antigen results in protective immunity against that pathogenic organism.
  • Bordetella pertussis fimbriae can be purified from culture of Bordetella pertussis (for example, EP-A-0231083 describes purification of pertussis antigens), or can be produced by recombinant techniques, and consequently reference to a fimbria of Bordetella pertussis is to be understood as a reference to a fimbria whether derived by purification of natural fimbriae or by recombinant expression of DNA encoding fimbriae, and is also to be understood to encompass variants, derivatives and fragments of fimbriae which are nevertheless recognised as being variants, derivatives or fragments of Bordetella pertussis fimbriae, as immunisation with such variants, derivatives or fragments results in induction of antibodies that are protective against challenge by Bordetella pertussis.
  • fimbriae in the range 10 ⁇ g-50//g is a typical vaccinating dose.
  • Purification and characterisation of fimbriae isolated from B. ertussis is also described by Zhang et al in Infection and Immunity, May 1 985, pp 422-427, and by Robinson et al in Vaccine, vol. 7, August 1 989 pp 31 2 onwards.
  • the carrier is conjugated to the antigen using a C6 spacer, in which the fimbriae are first derivatised and then added to a solution of antigen. It is also an option for the antigen first to be derivatised and this can be of advantage when the antigen is liable to be damaged by the derivatisation conditions, which typically include variations in pH.
  • a bifunctional group is introduced so as to link the two together.
  • an animal is immunised with a vaccine comprising the immunogenic conjugate and is protected against challenge by the pathogenic organism from which the antigen component of the conjugate has been derived.
  • protection is acknowledged by survival against a challenge with a lethal dose of the pathogenic organism, or by extended life expectancy in response to challenge with such a lethal dose. Protection is also acknowledged by a patient being less affected, less ill, following challenge by a sub-lethal dose of pertussis.
  • the invention is of advantage in that it provides an alternative carrier molecule for preparation of immunogenic conjugates for presentation of an antigen in combination with a T-cell epitope.
  • the immune response to the immunogenic conjugate of the invention is enhanced compared with the immune response against isolated antigen, thus improving the efficiency compared with vaccination by antigen alone.
  • the invention also provides an alternative to the existing toxoid carriers, and therefore overcomes the problem of toxoid overload which can occur with extended and repeated uses of vaccines containing these toxoids.
  • a further advantage of using pertussis fimbriae as a component of the conjugate is that they do not require detoxification prior to incorporation into a vaccine.
  • Detoxification which is required for the diphtheria and tetanus toxins used in the art, can alter the immunological properties of the protein.
  • a still further advantage is that fimbriae from Bordetella pertussis also confer or enhance projective immunity against Bordetella pertussis, a paediatrically relevant pathogen, and thus a conjugate comprising fimbriae induces a dual immune response.
  • the existing paediatric immunisation programme includes immunisation with DTP vaccine, conferring protection against diphtheria, tetanus and pertussis in a single vaccine.
  • the invention opens the possibility of incorporating a fourth component, which fourth component could be, for example, antigen conferring immunity against Haemophilus influenzae, into this three-component vaccine, by incorporating a conjugate vaccine according to the invention which confers immunity against both pertussis and a fourth pathogenic organism.
  • Pertussis toxoid is a further alternative component of the conjugate of the invention and offers the potential to act as an antigen carrier without contributing to the risk of tetanus/diphtheria toxoid overload experienced with prior art carriers, pertussis toxoid also offers vaccination against both the antigen and pertussis itself.
  • Pertussis toxin another alternative carrier, is optionally denatured or otherwise treated so as to render it non-toxic prior to administration to a patient. This step may be carried out prior to conjugation to antigen or after conjugation. Alternatively, toxin is used in a conjugate vaccine at a low, non-toxic dose.
  • 69kD protein another alternative carrier, is optionally produced by purification from culture or by recombinant means, and reference to 69kD protein is understood to encompass variants, derivatives and fragments of the protein that retain the essential immunogenicity of the intact protein.
  • the conjugate of the invention comprises an antigen.
  • the source or nature of the antigen is not limited to any particular sub-group of antigens, and indeed it is possible that the antigen in isolation is not immunogenic, but only becomes immunogenic which incorporated into the conjugate of the invention.
  • Suitable antigens include carbohydrates, polysaccharides, monosaccharides, oligosaccharides, proteins, peptides, glycopeptides, lipopolysaccharides and similar and related molecules.
  • the antigen will be, or will be derived from, a component of a bacteria or virus which appears on an outer surface of the bacteria or virus, such as a component of the bacterial cell wall, or a component of a fimbria or cilia or flagella, or a component of the outer envelope of a virus, a specific example of which is the surface antigen of hepatitis B virus.
  • the antigen can be a component of or derived from Bordetella bronchiseptica , Clostndium tetani, Cytomegalovirus, Dengue virus, Epstein-Barr virus, Flavivirus, Hepatitis A, B, C, D or E virus, Herpes Simplex virus, Influenza virus, JEV, Measles virus, Mumps virus, Mycobacteria tuberculosis, Rotavirus, Rubella virus, TBE, Vibrio cholerae, Haemophilus Influenzae, Neisseria meningitidis, Streptococcus pneumoniae, Staphylococcus A, B.parapertussis, HIV, HPV, polio virus, Brucella, Y.pestis, Helicobacter pylori , B. burgdorfeii, malaria and RSV though the invention is not to be construed as limited just to this sub-group of antigens.
  • the antigenic conjugate comprises a carrier of the invention, such as a fimbria from Bordetella pertussis, conjugated to two different antigens.
  • the conjugate is thus of use in conferring or enhancing protective immunity against pertussis, and also against each of the two different pathogenic organisms from which the different antigens conjugated to the fimbria are obtained or derived.
  • An immunogenic conjugate of the invention thus optionally comprises a fimbria of Bordetella pertussis to which Meningococcal C polysaccharide and Hib capsular carbohydrate have both been conjugated. This embodiment of the invention can therefore be used to confer protective immunity against three pathogenic organisms.
  • An advantage of this embodiment of the invention is that multiple immunities can be conferred via a single vaccine component, avoiding the need to prepare mixtures of individual vaccines and reducing the need for repeated and complex vaccination schedules using vaccines conferring immunity against just a single organism.
  • This embodiment of the invention is made possible by the physical structure of fimbriae which are long, multimeric molecules containing multiple locations at which antigens can conveniently be coupled.
  • the conjugates of the invention are suitable for incorporation into microparticles for delivery via a large variety of routes including oral delivery.
  • the preparation of such microparticles is described in EP-A-02661 1 9, EP-A-0333523 and EP-A-0706792, the contents of which are incorporated herein by reference.
  • a further embodiment of the invention comprises a mixture of two immunogenic conjugates, each conjugate comprising a different pertussis fimbria type conjugated to the same or to a different antigen.
  • the invention also provides a method of preparing a conjugate of a carrier selected from (i) a fimbria of Bordetella pertussis, (ii) a pertussis toxin, (Hi) a pertussis toxoid and (iv) pertussis 69kD protein with an antigen, the method comprising the steps of combining a preparation of the carrier with an antigen preparation so as covalently to conjugate the antigen to the carrier and thereafter recovering the conjugate from the mixture.
  • Conjugation is based on primary amine groups in the carrier molecule and thus conjugation of the carrier to the antigen is possible wherever these amine groups are available on the surface of the carrier. Where two or more such groups are available so a conjugate of carrier plus two antigens is possible.
  • lyophilised fimbriae are dissolved in a solution of antigen, which solution is then maintained at reduced temperature for an extended period of time so as to allow conjugation of the antigen to the fimbriae.
  • an amount of fimbriae are dissolved in acidic buffer, stabilised, dialysed and then lyophilised.
  • the antigen is prepared by dissolving the antigen in a suitable buffer and then the lyophilised fimbriae are added to that buffer, the resulting mixture is dialysed for an extended period of time and then the mixture is lyophilised and immunogenic conjugate recovered.
  • the invention relates also to use of the immunogenic conjugate of the invention, and thus the invention also provides use of the conjugate of the invention in manufacture of a medicament for vaccination of humans or animals against a pathogenic organism from which the antigen is derived or obtained.
  • the invention also provides a method of vaccination of humans or animals comprising administration to the human or animal of an effective immunising amount of the conjugate of the invention.
  • Vaccines incorporating the immunogenic conjugate of the invention can be formulated according to techniques that are standard in this art, and the vaccines can comprise conventional pharmaceutically acceptable carriers and excipients with which the skilled person will be familiar.
  • the immunogenic conjugates of the present invention may be prepared according to any conventional techniques for the covalent conjugating of antigens to carrier molecules and the invention is not to be construed as limited to the specific methods of conjugation that have been described and which are exemplified below.
  • a second aspect of the invention provides a vaccine against pertussis, comprising an oral formulation of a fimbria of Bordetella pertussis in a pharmaceutically acceptable carrier.
  • the meaning and ambit of reference to fimbria is as for the first aspect of the invention.
  • the invention also provides a method of vaccinating against pertussis by administering fimbriae or fimbriae-antigen conjugate orally, and to use of fimbriae or fimbriae-antigen conjugate in manufacture of a medicament for oral vaccination against pertussis.
  • fimbriae or fimbriae-antigen conjugate are formulated with a particulate carrier, typically being adsorbed onto or conjugated to the outside of the particles.
  • a particulate carrier typically being adsorbed onto or conjugated to the outside of the particles.
  • Polymers such as PLG and mineral particles may be used.
  • Bordetella pertussis fimbriae are adsorbed onto particles of 10 microns or less in diameter.
  • a suspension of mineral particles of 10 microns or less in diameter is suitable. Following oral administration uptake of these particles onto which have been absorbed fimbriae or fimbriae-antigen conjugate may occur via the Peyer's patches in the intestine.
  • an oral vaccinating composition comprises a colloidal suspension of alum onto which has been adsorbed fimbriae according to the invention.
  • the oral vaccine can be substantially free of antigenic or immunizing components other than the fimbriae or fimbriae-antigen conjugate.
  • Alum is a very known vaccine adjuvant, and to date exclusively used by injection. The inventors have found that when alum plus fimbriae are given orally a good immune response is obtained. The antibody response produced is enough to give protection and that protection includes both a serum response and a mucosal response. It is known in the art that systemic injection of vaccine gives a good serum response, principally IgG. It has been found that oral vaccination according to the second aspect of the invention gives both an IgG response and also an IgA response. This is significant because IgA appears on mucosal surfaces, which are the entry point for most pathogens.
  • the stomach of the patient is pre-neutralised, so that acid activated proteases do not destroy the vaccine components.
  • the vaccine of the invention is formulated so as to comprise an effective amount of a compound to neutralize stomach acid.
  • a vaccinating composition is formulated using bicarbonate buffer, specifically of strength 0.1 M, having a pH in the range 8.2-8.5, though other acid- neutralising solutions would also be expected to be suitable for the compositions of the invention.
  • a further option is for an acid-neutralising pharmaceutical to be administered prior to administration of the vaccine formulation.
  • an animal is administered orally with a formulation of the invention, and optionally is subsequently administered a booster dose of a formulation of the invention, and is thereby protected against pertussis.
  • M cells in the gut take up paniculate material, as part of a continuous gut content testing process, and pass their contents to lymph nodes and finally on to macrophages where the immune response is based. It is thought that alum particles pass into the M cells and thus join the chain leading to an immune response; though the applicant does not wish to be bound by this theory.
  • An oral vaccine of an embodiment of the invention comprises a suspension of a carrier adapted for passage or other transport to antigen presenting cells and fimbriae.
  • alum is the carrier a formulation as currently used in the art for injection is suitable.
  • a flavouring or sweetening agent is an optional addition.
  • the vaccine of the second aspect of the invention may also include a preservative, or an excipient which assists in freeze-drying the vaccine for easy, room temperature storage.
  • Fig. 1 shows serum anti-polysaccharide antibody responses from mice immunised on day 0, 14 and 28 with phosphate-buffered saline (PBS), fimbriae (Fim) or fimbriae-polysaccharide conjugate (Fim Conj) and tested for specific anti- polysaccharide antibodies on day 42;
  • PBS phosphate-buffered saline
  • Fim fimbriae
  • Fim Conj fimbriae-polysaccharide conjugate
  • Fig. 2 shows the serum anti-fimbriae antibody responses from mice immunised with phosphate-buffered saline (PBS), fimbriae (Fim) or fimbriae- polysaccharide conjugate (Fim Conj) and tested on day 21 for specific anti-fimbriae antibodies;
  • PBS phosphate-buffered saline
  • Fim fimbriae
  • Fim Conj fimbriae- polysaccharide conjugate
  • Fig. 3 shows the percent protection of mice, immunised with phosphate- buffered saline (Naive), fimbriae (Fim) or fimbria-meningococcal C polysaccharide conjugate (Fim Conj) and subsequently challenged with 10 6 cfu dose of B. pertussis;
  • Fig. 4 shows the number of survivors per group of five mice following challenge with Neisseria meningitidis on day 35 following immunisation by phosphate-buffered saline ( 1 ), fimbriae (2), fimbriae-meningococcal C conjugate (3) or AC vaccine (4), Fig. 4a showing the results following challenge by 10 6 cfu of bacteria and Fig. 4b showing the results following challenge by 10 8 cfu of bacteria;
  • Fig. 5 shows the numbers of mice surviving following challenge by 10 6 cfu meningitidis in control groups (1 ) and groups immunised with fimbriae (2), fimbriae- polysaccharide conjugate (3) and commercial ACVax (trade mark) vaccine (4);
  • Fig . 6 shows in vitro bactericidal titres following immunisation, legend as for Fig. 5;
  • Fig. 7 shows graphs of anti-fimbrial responses in external secretions elicited by oral alum-adjuvanted fimbriae: 7a-stools, 7b-vaginal washes, 7c-saliva;
  • Fig. 8 shows graphs of average protection elicited by orally administered alum-adjuvanted fimbriae
  • Fig. 9 shows graphs of anti-fimbrial responses in serum elicited by intraperitoneal or oral alum-adjuvanted fimbriae.
  • the method is essentially as described by Gotschlich, E. (1 975) . Purification of the group-specific polysaccharide. Monogr. Allergy 9, 245-258. Polysaccharide is purified from strain L91 543 (C2a P1 .2R, obtained from Manchester Public Health Laboratory) .
  • Bacteria are grown overnight on blood agar plates and inoculated into 100ml Frantz medium in 250ml conical flasks and incubated with shaking for 7h. Conical flasks containing 750ml Frantz medium are then inoculated with 10ml of the seed culture and incubated overnight with shaking at 37°C.
  • Centrifuge pots are filled to 1 L with culture and allowed to stand for 1 h at room temperature.
  • the bacteria and precipitated polysaccharide are then harvested by centrifugation (RC3B centrifuge, 5000rpm, 30min) and the supernatant is discarded.
  • pellets are resuspended in approx. 200ml H 2 O, homogenised to prepare a smooth suspension and an equal volume of 2M CaCI 2 added. This is stirred for 1 h to release the polysaccharide from the CTB complex.
  • the ethanol concentration is raised to 80% (v/v) to precipitate the polysaccharide.
  • the precipitate is then recovered by centrifugation (25,000g, 10min).
  • the precipitate is washed x4 with absolute ethanol to remove the CTB and the pellet resuspended in PBS ready for phenol extraction to remove contaminating protein.
  • a 90%(w/v) phenol solution is prepared by dissolving 90g phenol by adding 10ml boiling H 2 O and melting in a water bath at 56°.
  • the mixture is centrifuged in a bench centrifuge at 4100rpm for about 15min.
  • the phenol layer is re-extracted with PBS and incubated for 15min at room temperature. Centrifuge as above, remove the top aqueous layer and pool with the previous extract.
  • the aqueous extract is dialysed against 0.1M CaCI 2 , overnight to remove any remaining phenol.
  • the dialysed polysaccharide is centrifuged at 100,000g for 5h to pellet the lipooligosaccharide.
  • the precipitate is recovered by centrifugation and washed with absolute ethanol.
  • Stage 1 derivatisation of protein with adipic acid dihydrazide (ADH)
  • Stage 2 activation of polysaccharide and conjugation to derivatised protein.
  • the fimbriae it is not essential for the fimbriae to be derivatised, and instead the polysaccharide can be derivatised and this can sometimes minimise the exposure of more labile proteins to inclement conditions, such as low pH followed by high pH.
  • mice (6-8 weeks old) are immunised with polysaccharide conjugate vaccine on days 0, 1 4, 28 and then challenged with serogroup C N. meningitidis on day 35.
  • the challenge dose (0.5ml) is given by intra-peritoneal injection and contains 10 6 - 10 8 bacteria and iron dextran (2mg).
  • a further intra-peritoneal injection of 2mg iron dextran is also given at 24h following challenge.
  • the number of surviving mice in each group is recorded for 72h post infection.
  • Neisseria meningitidis serogroup C bactericidal assay The method used for Neisseria meningitidis serogroup C bactericidal assay is essentially the same as detailed in the Centers for Disease Control and Prevention protocol (Neisseria meningitidis serogroup A/C serum bactericidal assay, Maslanka et al., 1 995 CDC Atlanta, USA) with the following exceptions:
  • meningitidis strain G ⁇ is used for measurement of serogroup C bactericidal antibody.
  • agar "tilt" method only is used for enumeration of bacteria, 10 /I from each well of a 96 well assay plate is applied to BHI + 1 % horse serum plates.
  • Figs 1 and 2 show no specific anti-polysaccharide responses in mice immunised with phosphate-buffered saline or with fimbriae alone, and significant anti-polysaccharide responses in mice immunised with a conjugate with fimbriae and polysaccharide, though no IgA antibodies were observed.
  • Fig 2 shows the presence of specific anti-fimbriae antibodies in mice immunised both with fimbriae alone and also in mice immunised with the conjugate of fimbriae and polysaccharide.
  • Fig. 1 shows no specific anti-polysaccharide responses in mice immunised with phosphate-buffered saline or with fimbriae alone, and significant anti-polysaccharide responses in mice immunised with a conjugate with fimbriae and polysaccharide, though no IgA antibodies were observed.
  • Fig 2 shows the presence of specific anti-fimbriae antibodies in mice immunised both with
  • FIG. 3 shows there was effective protection against challenge by Bordetella pertussis following immunisation with pertussis fimbriae alone or fimbriae-polysaccharide conjugate.
  • Fig. 4 shows the number of survivors in a group of five mice immunised with phosphate-buffered saline, fimbriae, fimbriae-meningococcal C polysaccharide or a known vaccine.
  • Fig. 4a shows that 24 hours post-challenge the group immunised with the fimbriae-polysaccharide conjugate all survived, whereas only two survived from the groups immunised with phosphate-buffered saline or with fimbriae alone.
  • Fig. 4 shows that 24 hours post-challenge the group immunised with the fimbriae-polysaccharide conjugate all survived, whereas only two survived from the groups immunised with phosphate-buffered saline or with fi
  • mice were immunised with PBS (injected i/p), Fimbriae ( 10 ⁇ g injected i/p). Fimbriae-polysaccharide conjugate (10 ⁇ g protein + 10 ⁇ g polysaccharide injected i/p) or with a commercial meningococcal vaccine (ACVax, 1 0 ⁇ g polysaccharide injected i/m) . Animals were immunised on days 0, 14 & 28. Animals were challenged with a lethal dose of 1 0 6 cfu's of N. meningitidis on day 35. Bactericidal assays were performed as below on pre-challenge sera.
  • mice immunised with PBS or fimbriae were dead. 1 /5 mice given the commercial meningococcal vaccine survived at 48h while 3/5 mice immunised with the fimbriae-polysaccharide experimental conjugate vaccine survived (figure 5) .
  • the results of the bactericidal assay show that immunisation of mice with the experimental conjugate vaccine elicited in vitro bactericidal titres of 51 2 compared with 1 28 elicited by the commercial vaccine (figure 6) .
  • Formulations of fimbriae were prepared as follows. For oral administration, three volumes of fimbriae is diluted with one volume of commercially available alum adjuvant. A volume equivalent to 1 0 ⁇ g of fimbriae (20-100 ⁇ l) is diluted with four volumes of 0.1 M bicarbonate buffer (to a maximum volume of 500 ⁇ l), which has a pH of 8.2-8.5 and is designed to be acid-neutralising for oral administration, and suitable for administration by oral gavage. For I. P. administration, three volumes of antigen is diluted with one volume of commercially available adjuvant and a volume equivalent to 10 ⁇ g of fimbriae is injected. Formulations containing fimbriae - polysaccharide conjugate were similarly prepared.
  • Alum formulations as described in Example 3 were used in combination with pertussis fimbriae and administered to mice via i/p or oral routes, and when orally there was prior neutralising of gut acid. The results are illustrated in Fig.s 7, 8 and 9.
  • Fig. 7 shows that antibodies against fimbriae were found to include antibodies of IgG, IgM and IgA classes in stools (Fig. 7a), vaginal washes (Fig. 7b) and saliva (fig. 7c) .
  • Fig. 8 shows that immunisation (using 10 ⁇ g of fimbriae) via oral administration of fimbriae resulted in protection from challenge by B. pertussis, and comparable protection to that provided by i/p administration of fimbriae.
  • Anti- fimbrial responses in serum are shown in Fig. 9; though reduced in amount, serum response following oral administration was nevertheless significant.
  • microparticle pellet Resuspend in 25 ml of water as above, transfer to a vessel suitable for freeze drying, shell freeze and lyophilise for 48 h.
  • a vessel suitable for freeze drying, shell freeze and lyophilise for 48 h.
  • microparticles of about 2-5 ⁇ m diameter, for oral administration or incorporation into other vaccinating compositions.
  • the method is also suitable for encapsulation of fimbriae-antigen conjugate.
  • the invention provides an additional and alternative carrier to known toxoid antigen carriers and is of use in preparing novel conjugate vaccines for a wide range of immunisation applications.
  • Oral administration of fimbriae provides protective immunity against pertussis, and is of application to production of oral vaccines.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Immunology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne un conjugué de vaccination qui comprend un antigène conjugué à un support sélectionné entre la fimbria de Bordetella pertussis, la toxine de la coqueluche, l'anatoxine de coqueluche et la protéine 69kD de la coqueluche. Le conjugué peut aussi renfermer un second antigène, différent du premier. Une composition orale de vaccination comprend une fimbria de Bordetella pertussis ou un conjugué fimbria-antigène.
EP98930917A 1997-06-20 1998-06-22 Vaccin contenant un antigene de bordetella pertussis Withdrawn EP1005367A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB9713156.9A GB9713156D0 (en) 1997-06-20 1997-06-20 Vaccines
GB9713156 1997-06-20
PCT/GB1998/001819 WO1998058668A2 (fr) 1997-06-20 1998-06-22 VACCIN CONTENANT UN ANTIGENE DE $i(BORDETELLA PERTUSSIS)

Publications (1)

Publication Number Publication Date
EP1005367A2 true EP1005367A2 (fr) 2000-06-07

Family

ID=10814739

Family Applications (1)

Application Number Title Priority Date Filing Date
EP98930917A Withdrawn EP1005367A2 (fr) 1997-06-20 1998-06-22 Vaccin contenant un antigene de bordetella pertussis

Country Status (6)

Country Link
EP (1) EP1005367A2 (fr)
JP (1) JP2002508761A (fr)
AU (1) AU731216B2 (fr)
CA (1) CA2294348A1 (fr)
GB (1) GB9713156D0 (fr)
WO (1) WO1998058668A2 (fr)

Families Citing this family (195)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2283012T3 (es) 1996-01-04 2007-10-16 Novartis Vaccines And Diagnostics, Inc. Bacterioferritina de helicobacter pylori.
ATE452651T1 (de) * 1998-09-01 2010-01-15 Merrion Res Iii Ltd Orale impfstoff-zusammensetzung
DE69930753D1 (de) * 1998-09-01 2006-05-18 Elan Corp Plc Dublin Verfahren zur induktion der zellulären immunantwort und parenterale impfstoff-zusammensetzungen dazu
US7087236B1 (en) 1998-09-01 2006-08-08 Merrion Research I Limited Method for inducing a cell-mediated immune response and improved parenteral vaccine formulations thereof
GB0018031D0 (en) * 2000-07-21 2000-09-13 Microbiological Res Authority Improvements relating to vaccines containing bordetella pertussis antigen
MXPA03003690A (es) 2000-10-27 2004-05-05 Chiron Spa Acidos nucleicos y proteinas de los grupos a y b de estreptococos.
US7082569B2 (en) 2001-01-17 2006-07-25 Outlooksoft Corporation Systems and methods providing dynamic spreadsheet functionality
GB0107658D0 (en) 2001-03-27 2001-05-16 Chiron Spa Streptococcus pneumoniae
GB0107661D0 (en) 2001-03-27 2001-05-16 Chiron Spa Staphylococcus aureus
GB0115176D0 (en) 2001-06-20 2001-08-15 Chiron Spa Capular polysaccharide solubilisation and combination vaccines
GB0118249D0 (en) 2001-07-26 2001-09-19 Chiron Spa Histidine vaccines
GB0121591D0 (en) 2001-09-06 2001-10-24 Chiron Spa Hybrid and tandem expression of neisserial proteins
ES2312649T3 (es) 2001-12-12 2009-03-01 Novartis Vaccines And Diagnostics S.R.L. Inmunizacion frente a chlamydia trachomatis.
US7501134B2 (en) 2002-02-20 2009-03-10 Novartis Vaccines And Diagnostics, Inc. Microparticles with adsorbed polypeptide-containing molecules
NZ536859A (en) * 2002-05-14 2007-11-30 Chiron Srl Mucosal combination vaccines for bacterial meningitis
GB0302218D0 (en) 2003-01-30 2003-03-05 Chiron Sri Vaccine formulation & Mucosal delivery
MXPA04011249A (es) 2002-05-14 2005-06-06 Chiron Srl Vacunas mucosales con adyuvante de quitosano y antigenos meningococicos.
GB0220194D0 (en) 2002-08-30 2002-10-09 Chiron Spa Improved vesicles
WO2004032958A1 (fr) 2002-10-11 2004-04-22 Chiron Srl Vaccins polypeptidiques offrant une large protection contre des lignees de meningocoques hypervirulentes
ES2649048T3 (es) 2002-11-01 2018-01-09 Glaxosmithkline Biologicals S.A. Procedimiento de secado
EP2279746B1 (fr) 2002-11-15 2013-10-02 Novartis Vaccines and Diagnostics S.r.l. Proteines de surface de neisseria meningitidis
GB0227346D0 (en) 2002-11-22 2002-12-31 Chiron Spa 741
JP2006520746A (ja) 2002-12-27 2006-09-14 カイロン コーポレイション リン脂質を含む免疫原性組成物
WO2004067030A2 (fr) 2003-01-30 2004-08-12 Chiron Srl Vaccins injectables contre les multiples serogroupes du meningocoque
CA2520124A1 (fr) 2003-03-28 2004-10-14 Chiron Corporation Utilisation de composes de benzazole pour l' immunostimulation
PL1631264T5 (pl) 2003-06-02 2018-09-28 Glaxosmithkline Biologicals Sa Kompozycje immunogenne oparte na biodegradowalnych mikrocząstkach zawierających toksoid błonicy i tężca
ATE506963T1 (de) 2003-10-02 2011-05-15 Novartis Vaccines & Diagnostic Kombinationsimpfstoffe gegen meningitis
GB0323103D0 (en) 2003-10-02 2003-11-05 Chiron Srl De-acetylated saccharides
GB0406013D0 (en) 2004-03-17 2004-04-21 Chiron Srl Analysis of saccharide vaccines without interference
GB0408978D0 (en) 2004-04-22 2004-05-26 Chiron Srl Meningococcal fermentation for preparing conjugate vaccines
GB0409745D0 (en) 2004-04-30 2004-06-09 Chiron Srl Compositions including unconjugated carrier proteins
GB0410866D0 (en) 2004-05-14 2004-06-16 Chiron Srl Haemophilius influenzae
GB0411387D0 (en) 2004-05-21 2004-06-23 Chiron Srl Analysis of saccharide length
GB0413868D0 (en) 2004-06-21 2004-07-21 Chiron Srl Dimensional anlaysis of saccharide conjugates
WO2006115509A2 (fr) 2004-06-24 2006-11-02 Novartis Vaccines And Diagnostics Inc. Immuno-potentialisateurs a petites molecules et analyses visant a detecter leur presence
WO2006002422A2 (fr) 2004-06-24 2006-01-05 Novartis Vaccines And Diagnostics Inc. Composes utilises pour l'immunopotentialisation
EP2612679A1 (fr) 2004-07-29 2013-07-10 Novartis Vaccines and Diagnostics, Inc. Compositions immunogènes pour une bactérie à gram positif telle que streptococcus agalactiae
GB0424092D0 (en) 2004-10-29 2004-12-01 Chiron Srl Immunogenic bacterial vesicles with outer membrane proteins
GB0502095D0 (en) 2005-02-01 2005-03-09 Chiron Srl Conjugation of streptococcal capsular saccharides
GB0502096D0 (en) 2005-02-01 2005-03-09 Chiron Srl Purification of streptococcal capsular polysaccharide
SI2351772T1 (sl) 2005-02-18 2016-11-30 Glaxosmithkline Biologicals Sa Proteini in nukleinske kisline iz Escherichia coli povezane z meningitisom/sepso
CN101203529A (zh) 2005-02-18 2008-06-18 诺华疫苗和诊断公司 来自脑膜炎/脓毒症相关性大肠杆菌的蛋白质和核酸
WO2006113528A2 (fr) 2005-04-18 2006-10-26 Novartis Vaccines And Diagnostics Inc. Procede pour exprimer un antigene de surface de virus de l'hepatite b afin de preparer un vaccin
KR101408113B1 (ko) 2005-06-27 2014-06-16 글락소스미스클라인 바이오로지칼즈 에스.에이. 백신 제조 방법
BRPI0615420A2 (pt) 2005-09-01 2011-05-17 Novartis Vaccines & Diagnostic vacinação múltipla que inclui meningococo do sorogrupo c
GB0522765D0 (en) 2005-11-08 2005-12-14 Chiron Srl Combination vaccine manufacture
WO2007081447A2 (fr) 2005-11-22 2007-07-19 Novartis Vaccines And Diagnostics, Inc. Antigènes de norovirus et de sapovirus
GB0524066D0 (en) 2005-11-25 2006-01-04 Chiron Srl 741 ii
GB0607088D0 (en) 2006-04-07 2006-05-17 Glaxosmithkline Biolog Sa Vaccine
CA2808919C (fr) 2005-12-22 2016-04-19 Glaxosmithkline Biologicals S.A. Vaccin comportant des conjugues polysaccharides capsulaires streptococcus pneumoniae
NZ572054A (en) 2006-03-22 2011-12-22 Novartis Ag Regimens for immunisation with meningococcal conjugates
GB0605757D0 (en) 2006-03-22 2006-05-03 Chiron Srl Separation of conjugated and unconjugated components
ES2536426T3 (es) 2006-03-23 2015-05-25 Novartis Ag Compuestos de imidazoquinoxalina como inmunomoduladores
US20110206692A1 (en) 2006-06-09 2011-08-25 Novartis Ag Conformers of bacterial adhesins
GB0612854D0 (en) 2006-06-28 2006-08-09 Novartis Ag Saccharide analysis
JP2010500399A (ja) 2006-08-16 2010-01-07 ノバルティス アーゲー 尿路病原性大腸菌由来の免疫原
AU2007293673B2 (en) 2006-09-07 2013-06-27 Glaxosmithkline Biologicals S.A. Vaccine
GB0700136D0 (en) 2007-01-04 2007-02-14 Glaxosmithkline Biolog Sa Process for manufacturing vaccines
GB0700562D0 (en) 2007-01-11 2007-02-21 Novartis Vaccines & Diagnostic Modified Saccharides
EP2142211A1 (fr) 2007-05-02 2010-01-13 GlaxoSmithKline Biologicals S.A. Vaccin
EP2687228B1 (fr) 2007-06-26 2017-07-19 GlaxoSmithKline Biologicals S.A. Vaccin contenant des conjugues de polysaccharide capsulaire de streptococcus pneumoniae
GB0713880D0 (en) 2007-07-17 2007-08-29 Novartis Ag Conjugate purification
GB0714963D0 (en) 2007-08-01 2007-09-12 Novartis Ag Compositions comprising antigens
KR101621837B1 (ko) 2007-09-12 2016-05-17 노파르티스 아게 Ｇａｓ57 돌연변이 항원 및 ｇａｓ57 항체
JP5701058B2 (ja) 2007-10-19 2015-04-15 ノバルティス アーゲー 髄膜炎菌ワクチン処方物
GB0818453D0 (en) 2008-10-08 2008-11-12 Novartis Ag Fermentation processes for cultivating streptococci and purification processes for obtaining cps therefrom
CN104292312A (zh) 2007-12-21 2015-01-21 诺华股份有限公司 链球菌溶血素o的突变形式
NZ587382A (en) 2008-02-21 2012-01-12 Novartis Ag Meningococcal fhbp polypeptides
ES2586308T3 (es) 2008-10-27 2016-10-13 Glaxosmithkline Biologicals Sa Procedimiento de purificación de un hidrato de carbono de Streptococcus del grupo A
GB0822633D0 (en) 2008-12-11 2009-01-21 Novartis Ag Formulation
GB0822634D0 (en) 2008-12-11 2009-01-21 Novartis Ag Meningitis vaccines
US8585505B2 (en) 2008-12-15 2013-11-19 Tetris Online, Inc. Inter-game interactive hybrid asynchronous computer game infrastructure
AU2009329193A1 (en) 2008-12-17 2011-07-14 Novartis Ag Meningococcal vaccines including hemoglobin receptor
AU2010203223B9 (en) 2009-01-05 2015-10-08 Epitogenesis Inc. Adjuvant compositions and methods of use
AU2010204139A1 (en) 2009-01-12 2011-08-11 Novartis Ag Cna_B domain antigens in vaccines against gram positive bacteria
NZ595234A (en) 2009-03-24 2013-12-20 Novartis Ag Adjuvanting meningococcal factor h binding protein
CA2756533A1 (fr) 2009-03-24 2010-09-30 Novartis Ag Combinaisons de proteine liant le facteur h de meningocoque et de conjugues de saccharide de pneumocoque
PL2510947T3 (pl) 2009-04-14 2016-09-30 Kompozycje do immunizacji przeciwko Staphylococcus aureus
WO2010125480A1 (fr) 2009-04-30 2010-11-04 Coley Pharmaceutical Group, Inc. Vaccin anti-pneumococcique et ses utilisations
WO2010132833A1 (fr) 2009-05-14 2010-11-18 The Regents Of The University Of Michigan Compositions vaccinales contre streptococcus et méthodes d'utilisation associées
WO2011024072A2 (fr) 2009-08-27 2011-03-03 Novartis Ag Polypeptides hybrides contenant des séquences fhbp à méningocoques
ES2670576T3 (es) 2009-09-03 2018-05-31 Pfizer Vaccines Llc Vacuna de PCSK9
CN102695523A (zh) 2009-09-10 2012-09-26 诺华有限公司 针对呼吸道疾病的组合疫苗
CA2779798C (fr) 2009-09-30 2019-03-19 Novartis Ag Conjugaison de polysaccharides capsulaires de staphylococcus aureus de type 5 et de type 8
AU2010302344A1 (en) 2009-09-30 2012-04-26 Novartis Ag Expression of meningococcal fhbp polypeptides
BR112012010531A2 (pt) 2009-10-27 2019-09-24 Novartis Ag "polipeptídeos de modificação meningocócica fhbp"
JP5914344B2 (ja) 2009-10-30 2016-05-11 ノバルティス アーゲー Ｓｔａｐｈｙｌｏｃｏｃｃｕｓａｕｒｅｕｓ５型および８型の莢膜糖の精製
GB0919690D0 (en) 2009-11-10 2009-12-23 Guy S And St Thomas S Nhs Foun compositions for immunising against staphylococcus aureus
GB201003333D0 (en) 2010-02-26 2010-04-14 Novartis Ag Immunogenic proteins and compositions
GB201003922D0 (en) 2010-03-09 2010-04-21 Glaxosmithkline Biolog Sa Conjugation process
GB201005625D0 (en) 2010-04-01 2010-05-19 Novartis Ag Immunogenic proteins and compositions
EP2585106A1 (fr) 2010-06-25 2013-05-01 Novartis AG Associations de protéines de liaison du facteur h méningococcique
GB201101665D0 (en) 2011-01-31 2011-03-16 Novartis Ag Immunogenic compositions
WO2012072769A1 (fr) 2010-12-01 2012-06-07 Novartis Ag Epitopes rrgb de pneumocoque et combinaisons de variantes
EP2655389A2 (fr) 2010-12-24 2013-10-30 Novartis AG Composés
EP2667852B1 (fr) 2011-01-27 2016-11-09 GlaxoSmithKline Biologicals SA Nanoémulsions d'adjuvant à inhibiteurs de cristallisation
EP2680885B8 (fr) 2011-03-02 2018-07-25 GlaxoSmithKline Biologicals SA Vaccins combinés comprenant des doses inférieures d'antigène et/ou d'adjuvant
WO2012131504A1 (fr) 2011-03-02 2012-10-04 Pfizer Inc. Vaccin à base de pcsk9
GB201103836D0 (en) 2011-03-07 2011-04-20 Glaxosmithkline Biolog Sa Conjugation process
WO2012129483A1 (fr) 2011-03-24 2012-09-27 Novartis Ag Nanoémulsions adjuvantes avec des phospholipides
EP2511295A1 (fr) 2011-04-15 2012-10-17 Institut National De La Sante Et De La Recherche Medicale Compositions pour la prévention et/ou le traitement d'une infection par un virus VIH-1
BR112013032410A2 (pt) 2011-06-24 2017-01-17 Epitogenesis Inc composições farmacêuticas compreendendo uma combinação de veículos, vitaminas, taninos e flavonoides de seleção como imunomoduladores específicos de antígeno
WO2013009564A1 (fr) 2011-07-08 2013-01-17 Novartis Ag Procédé de ligature de la tyrosine
GB201114923D0 (en) 2011-08-30 2011-10-12 Novartis Ag Immunogenic proteins and compositions
WO2013038375A2 (fr) 2011-09-14 2013-03-21 Novartis Ag Procédés de production de glycoconjugués de saccharide-protéine
AU2012335208B2 (en) 2011-11-07 2017-08-31 Glaxosmithkline Biologicals S.A. Carrier molecule comprising a spr0096 and a spr2021 antigen
DE102011122891B4 (de) 2011-11-11 2014-12-24 Novartis Ag Fermentationsmedium, das frei von tierischen Bestandteilen ist, zur Herstellung von Diphtherie-Toxoiden zur Verwendung bei der Impfung von Menschen
EP2592137A1 (fr) 2011-11-11 2013-05-15 Novartis AG Support de fermentation sans composants dérivés d'animaux pour la production des toxoïdes diphtériques adaptées à l'utilisation du vaccin humain
DE102011118371B4 (de) 2011-11-11 2014-02-13 Novartis Ag Zur Impfung von Menschen geeignete Zusammensetzung, die ein Diphtherie-Toxoid umfasst, sowie Verfahren zu deren Herstellung
GB2495341B (en) 2011-11-11 2013-09-18 Novartis Ag Fermentation methods and their products
SG11201402375VA (en) 2011-12-08 2014-10-30 Novartis Ag Clostridium difficile toxin-based vaccine
GB201121301D0 (en) 2011-12-12 2012-01-25 Novartis Ag Method
US10596246B2 (en) 2011-12-29 2020-03-24 Glaxosmithkline Biological Sa Adjuvanted combinations of meningococcal factor H binding proteins
AU2013224026A1 (en) 2012-02-24 2014-08-21 Novartis Ag Pilus proteins and compositions
JP2015510872A (ja) 2012-03-07 2015-04-13 ノバルティス アーゲー Ｓｔｒｅｐｔｏｃｏｃｃｕｓｐｎｅｕｍｏｎｉａｅ抗原の増強された製剤
CN104159603A (zh) 2012-03-08 2014-11-19 诺华股份有限公司 带有tlr4激动剂的联合疫苗
SA115360586B1 (ar) 2012-03-09 2017-04-12 فايزر انك تركيبات لعلاج الالتهاب السحائي البكتيري وطرق لتحضيرها
RU2727476C2 (ru) 2012-04-26 2020-07-21 Новартис Аг Антигены и антигенные композиции
US10279026B2 (en) 2012-04-26 2019-05-07 Glaxosmithkline Biologicals Sa Antigens and antigen combinations
JP2015518845A (ja) 2012-05-22 2015-07-06 ノバルティス アーゲー 髄膜炎菌血清群ｘコンジュゲート
RU2015106930A (ru) 2012-09-06 2016-10-20 Новартис Аг Комбинированные вакцины с менингококком серогруппы в и к/д/с
US9855324B2 (en) 2012-10-03 2018-01-02 Glaxosmithkline Biologicals Sa Immunogenic compositions
BR112015008040A2 (pt) 2012-10-12 2017-07-04 Glaxosmithkline Biologicals Sa composição de vacina, vacina de combinação, e, processos para preparar um componente ap e para a fabricação de uma composição de vacina
ES2826555T3 (es) 2012-11-30 2021-05-18 Glaxosmithkline Biologicals Sa Antígenos de Pseudomonas y combinación de antígenos
CN105188747A (zh) 2013-02-01 2015-12-23 葛兰素史密斯克莱生物公司 包含toll样受体激动剂的免疫组合物的皮内递送
DK2863943T3 (en) * 2013-03-08 2016-11-07 Janssen Vaccines & Prevention Bv acellular pertussis vaccines
CA2923129C (fr) 2013-09-08 2020-06-09 Pfizer Inc. Compositions utilisables contre neisseria meningitidis et procedes associes
US11708411B2 (en) 2013-12-20 2023-07-25 Wake Forest University Health Sciences Methods and compositions for increasing protective antibody levels induced by pneumococcal polysaccharide vaccines
PL3096785T3 (pl) 2014-01-21 2021-03-08 Pfizer Inc. Kompozycje immunogenne zawierające skoniugowane antygeny sacharydów otoczkowych i ich zastosowania
RU2710393C2 (ru) 2014-01-21 2019-12-26 Пфайзер Инк. Способ получения иммуногенного конъюгата капсульный полисахарид Streptococcus pneumoniae-белок-носитель
PL3583947T3 (pl) 2014-01-21 2024-04-02 Pfizer Inc. Polisacharydy otoczkowe streptococcus pneumoniae i ich koniugaty
US11160855B2 (en) 2014-01-21 2021-11-02 Pfizer Inc. Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof
EP3443983B1 (fr) 2014-02-14 2022-07-20 Pfizer Inc. Conjugués immunogènes de glycoprotéine
BR112016019735A2 (pt) 2014-02-28 2017-10-17 Glaxosmithkline Biologicals Sa fhbp, polipeptídeo, plasmídeo ou outro ácido nucleico, célula hospedeira, vesículas de membrana, e, composição imunogênica
EP3034516A1 (fr) 2014-12-19 2016-06-22 Novartis AG Purification de polysaccharides capsulaires de streptocoques
EP3244917B1 (fr) 2015-01-15 2023-04-19 Pfizer Inc. Compositions immunogènes destinées à être utilisées dans des vaccins antipneumococciques
WO2016184963A1 (fr) 2015-05-19 2016-11-24 Innavirvax Traitement de patients souffrant d'une infection par le vih
WO2016184962A1 (fr) 2015-05-19 2016-11-24 Innavirvax Traitement de patients souffrant d'une infection par le vih
EP3109255A1 (fr) 2015-06-26 2016-12-28 Institut National De La Recherche Agronomique Composition immunogène
MY192183A (en) 2015-07-21 2022-08-05 Pfizer Immunogenic compositions comprising conjugated capsular saccharide antigens, kits comprising the same and uses thereof
GB201518684D0 (en) 2015-10-21 2015-12-02 Glaxosmithkline Biolog Sa Vaccine
JP6884145B2 (ja) 2015-11-20 2021-06-09 ファイザー・インク 肺炎連鎖球菌ワクチンにおいて用いるための免疫原性組成物
MX2018006785A (es) 2015-12-04 2018-11-09 Dana Farber Cancer Inst Inc Vacunacion con el dominio alfa 3 de mica/b para el tratamiento del cancer.
EP3439704A1 (fr) 2016-04-05 2019-02-13 GSK Vaccines S.r.l. Compositions immunogènes
JP7104027B2 (ja) 2016-09-02 2022-07-20 グラクソスミスクライン バイオロジカルズ ソシエテ アノニム 淋菌に対するワクチン
EP3522915A2 (fr) 2016-10-07 2019-08-14 Enterome S.A. Composés immunogéniques pour la thérapie du cancer
EP3522916A2 (fr) 2016-10-07 2019-08-14 Enterome S.A. Composés immunogéniques pour la thérapie du cancer
US20210108002A1 (en) 2016-12-06 2021-04-15 Glaxosmithkline Biologicals Sa Purification Process For Capsular Polysaccharide
CN110198735A (zh) 2017-01-20 2019-09-03 辉瑞公司 用于肺炎球菌疫苗中的免疫原性组合物
US20200222550A1 (en) 2017-01-31 2020-07-16 Merck Sharp & Dohme Corp. Methods for production of capsular polysaccharide protein conjugates from streptococcus pneumoniae serotype 19f
CN110234658B (zh) 2017-01-31 2024-03-12 辉瑞大药厂 脑膜炎奈瑟菌组合物及其使用方法
CN111093650B (zh) 2017-09-07 2024-03-01 默沙东有限责任公司 肺炎球菌多糖及其在免疫原性多糖-载体蛋白缀合物中的用途
GEP20227420B (en) 2017-12-06 2022-10-10 Merck Sharp & Dohme Llc Compositions comprising streptococcus pneumoniae polysaccharide-protein conjugates and methods of use thereof
US20210106652A1 (en) 2018-04-11 2021-04-15 Enterome S.A. Immunogenic Compounds For Treatment Of Fibrosis, Autoimmune Diseases And Inflammation
EP3773689B1 (fr) 2018-04-11 2022-11-09 Enterome S.A. Peptides antigéniques pour la prévention et le traitement du cancer
JP7446279B2 (ja) 2018-07-19 2024-03-08 グラクソスミスクライン バイオロジカルズ ソシエテ アノニム 乾燥多糖を調製するための方法
EP3607967A1 (fr) 2018-08-09 2020-02-12 GlaxoSmithKline Biologicals S.A. Polypeptides modifiés du méningocoque fhbp
US11260119B2 (en) 2018-08-24 2022-03-01 Pfizer Inc. Escherichia coli compositions and methods thereof
JP2022512345A (ja) 2018-12-12 2022-02-03 ファイザー・インク 免疫原性多重ヘテロ抗原多糖－タンパク質コンジュゲートおよびその使用
JOP20210148A1 (ar) 2018-12-19 2023-01-30 Merck Sharp & Dohme تركيبات تشتمل على متقارنات بولي سكاريد-بروتين للمكورات العقدية الرئوية وطرق استخدامها
WO2020165711A1 (fr) 2019-02-11 2020-08-20 Pfizer Inc. COMPOSITIONS DE NEISSERIA MENINGITIDIS<i /> ET PROCÉDÉS ASSOCIÉES
JP7239509B6 (ja) 2019-02-22 2023-03-28 ファイザー・インク 細菌多糖類を精製するための方法
CA3136278A1 (fr) 2019-04-10 2020-10-15 Pfizer Inc. Compositions immunogenes comprenant des antigenes saccharidiques capsulaires conjugues, kits les comprenant et leurs utilisations
CA3139257A1 (fr) 2019-05-10 2020-11-19 Glaxosmithkline Biologicals Sa Production de conjugues
KR20220042378A (ko) 2019-07-31 2022-04-05 사노피 파스퇴르 인코포레이티드 다가 폐렴구균 다당류-단백질 접합체 조성물 및 그 사용 방법
EP4034157A1 (fr) 2019-09-27 2022-08-03 Pfizer Inc. Compositions de neisseria meningitidis et méthodes associées
BR112022007203A2 (pt) 2019-10-16 2022-07-05 Enterome S A Compostos imunogênicos para tratamento de câncer adrenal
KR20220092572A (ko) 2019-11-01 2022-07-01 화이자 인코포레이티드 에스케리키아 콜라이 조성물 및 그 방법
BR112022009100A2 (pt) 2019-11-15 2022-07-26 Enterome S A Peptídeos antigênicos para prevenção e tratamento de malignidade de células b
CA3161857A1 (fr) 2019-11-22 2021-05-27 Glaxosmithkline Biologicals Sa Dosage et administration d'un vaccin a base de glycoconjugue de saccharide bacterien
CA3171864A1 (fr) 2020-02-21 2021-08-26 Pfizer Inc. Purification de saccharides
CN115605498A (zh) 2020-02-23 2023-01-13 辉瑞公司（Us） 大肠杆菌组合物及其方法
US20230250142A1 (en) 2020-06-12 2023-08-10 Glaxosmithkline Biologicals Sa Dock tag system
GB202013262D0 (en) 2020-08-25 2020-10-07 Glaxosmithkline Biologicals Sa Vaccine Composition
EP4232593A1 (fr) 2020-10-22 2023-08-30 Pfizer Inc. Procédés de purification de polysaccharides bactériens
MX2023004912A (es) 2020-10-27 2023-05-16 Pfizer Composiciones de escherichia coli y metodos de las mismas.
KR20230097160A (ko) 2020-11-04 2023-06-30 화이자 인코포레이티드 폐렴구균 백신에 사용하기 위한 면역원성 조성물
US20220202923A1 (en) 2020-12-23 2022-06-30 Pfizer Inc. E. coli fimh mutants and uses thereof
TW202245835A (zh) 2021-02-04 2022-12-01 美商默沙東有限責任公司 用於肺炎球菌結合物疫苗之奈米乳化液佐劑組合物
EP4070814A1 (fr) 2021-04-07 2022-10-12 Lama France Polypeptides sars-cov-2 et leurs utilisations
WO2022234416A1 (fr) 2021-05-03 2022-11-10 Pfizer Inc. Vaccination contre des infections à pneumocoque et à covid-19
CA3218544A1 (fr) 2021-05-03 2022-11-10 Pfizer Inc. Vaccination contre des infections bacteriennes et a betacoronavirus
TW202306969A (zh) 2021-05-28 2023-02-16 美商輝瑞大藥廠 包含結合之莢膜醣抗原的免疫原組合物及其用途
BR112023023671A2 (pt) 2021-05-28 2024-02-06 Pfizer Composições imunogênicas compreendendo antígenos de sacarídeo capsular conjugados e usos dos mesmos
WO2023135515A1 (fr) 2022-01-13 2023-07-20 Pfizer Inc. Compositions immunogènes à base d'antigènes saccharidiques capsulaires conjugués et leurs utilisations
WO2023161817A1 (fr) 2022-02-25 2023-08-31 Pfizer Inc. Procédés d'incorporation de groupes azido dans des polysaccharides capsulaires bactériens
WO2023187127A1 (fr) 2022-03-31 2023-10-05 Enterome S.A. Peptides antigéniques pour la prévention et le traitement du cancer
WO2023218322A1 (fr) 2022-05-11 2023-11-16 Pfizer Inc. Procédé de production de formulations de vaccin avec des conservateurs
GB202208089D0 (en) 2022-06-01 2022-07-13 Glaxosmithkline Biologicals Sa Immunogenic composition
GB202208093D0 (en) 2022-06-01 2022-07-13 Glaxosmithkline Biologicals Sa Immunogenic composition
WO2024064579A1 (fr) * 2022-09-20 2024-03-28 Ohio State Innovation Foundation Protéines immunogènes provenant de bordetella pertussis
WO2024084397A1 (fr) 2022-10-19 2024-04-25 Pfizer Inc. Vaccination contre infections à pneumocoques et à covid-19
WO2024110827A1 (fr) 2022-11-21 2024-05-30 Pfizer Inc. Procédés de préparation d'antigènes saccharidiques capsulaires conjugués et leurs utilisations
WO2024110839A2 (fr) 2022-11-22 2024-05-30 Pfizer Inc. Compositions immunogènes comprenant des antigènes saccharidiques capsulaires conjugués et leurs utilisations
WO2024116096A1 (fr) 2022-12-01 2024-06-06 Pfizer Inc. Formulations de vaccin pneumococcique conjugué

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0399001B1 (fr) * 1988-02-01 1994-07-27 Praxis Biologics, Inc. Epitopes de cellules t a titre de molecules porteuses pour vaccins conjugues
US5101014A (en) * 1989-02-10 1992-03-31 United States Of America Process for the purification of a 69,000 da outer membrane protein of Bordetella pertussis
IT1248735B (it) * 1990-06-21 1995-01-26 Sclavo Spa Vaccini acellulari contro la pertosse
JP2631035B2 (ja) * 1991-03-12 1997-07-16 アメリカ合衆国 多糖類−タンパク質複合体
PT658118E (pt) * 1992-08-31 2002-05-31 Baxter Healthcare Sa Vacinas contra neisseria meningitidis do grupo c

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9858668A2 *

Also Published As

Publication number Publication date
CA2294348A1 (fr) 1998-12-30
AU731216B2 (en) 2001-03-29
JP2002508761A (ja) 2002-03-19
WO1998058668A2 (fr) 1998-12-30
WO1998058668A3 (fr) 1999-04-15
AU8119498A (en) 1999-01-04
GB9713156D0 (en) 1997-08-27

Similar Documents

Publication Publication Date Title
AU731216B2 (en) Vaccines containing bordetella pertussis antigen
US9168313B2 (en) Vaccine
JP4696260B2 (ja) キトサンアジュンバントおよび髄膜炎菌抗原を用いる粘膜ワクチン
RU2378008C2 (ru) Комбинированные вакцины против бактериального менингита для введения через слизистую оболочку
JP6266631B2 (ja) 免疫原性組成物
JP2004501873A5 (fr)
JP2010209122A (ja) キトサンアジュンバントおよび髄膜炎菌抗原を用いる粘膜ワクチン
CA2090673A1 (fr) Compositons de vaccin ameliorees
JP2022515098A (ja) ストレプトコッカス・ニューモニエ多糖－タンパク質コンジュゲートを含む組成物およびその使用方法
JPH04230634A (ja) 複合ワクチンのキヤリヤー分子としての、百日咳菌の繊維状赤血球凝集素
EP2313116A1 (fr) Compositions de conjugués polysaccharide-polypeptide bactériens améliorées
WO2002007764A1 (fr) Ameliorations portant sur des vaccins contenant un antigene contre bordetella pertussis
Eskola Use of conjugate vaccines to prevent meningitis caused by Haemophilus influenzae type b or Streptococcus pneumoniae
US20150079129A1 (en) Vaccine
Pozsgay Bacterial polysaccharide-protein conjugate
Makela et al. Vaccines Against Bacterial Infections of Children
MXPA01009455A (en) Vaccine
MXPA06015159A (es) Composiciones de vacuna libres de adyuvante que contienen porinas de salmonella enterica serovar typhi.

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19991215

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

17Q First examination report despatched

Effective date: 20030704

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: HEALTH PROTECTION AGENCY

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20050311