US20030180316A1 - Multivalent vaccine composition - Google Patents

Multivalent vaccine composition Download PDF

Info

Publication number
US20030180316A1
US20030180316A1 US10/312,090 US31209003A US2003180316A1 US 20030180316 A1 US20030180316 A1 US 20030180316A1 US 31209003 A US31209003 A US 31209003A US 2003180316 A1 US2003180316 A1 US 2003180316A1
Authority
US
United States
Prior art keywords
capsular polysaccharide
immunogenic composition
pneumoniae serotype
group
meningitidis
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.)
Abandoned
Application number
US10/312,090
Other languages
English (en)
Inventor
Dominique Boutriau
Carine Capiau
Pierre Desmons
Dominique Lemoine
Jan Poolman
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.)
GlaxoSmithKline Biologicals SA
Original Assignee
GlaxoSmithKline Biologicals SA
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27255788&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=US20030180316(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from GBGB0015999.6A external-priority patent/GB0015999D0/en
Priority claimed from GBGB0108364.1A external-priority patent/GB0108364D0/en
Priority claimed from GB0108363A external-priority patent/GB0108363D0/en
Application filed by GlaxoSmithKline Biologicals SA filed Critical GlaxoSmithKline Biologicals SA
Assigned to GLAXOSMITHKLINE BIOLOGICALS S.A. (FORMERLY SMITHKLINE BEECHAM BIOLOGICALS S.A.) reassignment GLAXOSMITHKLINE BIOLOGICALS S.A. (FORMERLY SMITHKLINE BEECHAM BIOLOGICALS S.A.) ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: DESMONS, PIERRE MICHEL, POOLMAN, JAN, BOUTRIAU, DOMINIQUE, LEMOINE, DOMINIQUE, CAPIAU, CARINE
Publication of US20030180316A1 publication Critical patent/US20030180316A1/en
Priority to US13/439,829 priority Critical patent/US9233151B2/en
Abandoned legal-status Critical Current

Links

Images

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
    • A61K39/0016—Combination vaccines based on diphtheria-tetanus-pertussis
    • A61K39/0018—Combination vaccines based on acellular diphtheria-tetanus-pertussis
    • 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
    • A61K39/09—Lactobacillales, e.g. aerococcus, enterococcus, lactobacillus, lactococcus, streptococcus
    • A61K39/092—Streptococcus
    • 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
    • A61K39/102—Pasteurellales, e.g. Actinobacillus, Pasteurella; Haemophilus
    • 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
    • A61K39/12—Viral antigens
    • 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
    • A61K39/12—Viral antigens
    • A61K39/125—Picornaviridae, e.g. calicivirus
    • A61K39/13—Poliovirus
    • 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
    • A61K39/12—Viral antigens
    • A61K39/29—Hepatitis virus
    • 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
    • A61K39/12—Viral antigens
    • A61K39/29—Hepatitis virus
    • A61K39/292—Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • 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
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • 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
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • 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
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525—Virus
    • A61K2039/5252—Virus inactivated (killed)
    • 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
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • 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
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55583—Polysaccharides
    • 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
    • A61K2039/6037—Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2730/00—Reverse transcribing DNA viruses
    • C12N2730/00011—Details
    • C12N2730/10011—Hepadnaviridae
    • C12N2730/10111—Orthohepadnavirus, e.g. hepatitis B virus
    • C12N2730/10134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/32011—Picornaviridae
    • C12N2770/32611—Poliovirus
    • C12N2770/32634—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • 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 new combination vaccine formulations.
  • Combination vaccines which provide protection against multiple pathogens
  • the well-documented phenomenon of antigenic competition (or interference) complicates the development of multi-component vaccines.
  • Antigenic interference refers to the observation that administering multiple antigens often results in a diminished response to certain antigens relative to the immune response observed when such antigens are administered individually.
  • Combination vaccines are known which can prevent Bordetella pertussis, Clostridium tetani, Corynebacterium diphtheriae , and optionally Hepatitis B virus and/or Haemophilus influenzae type b (see, for instance, WO 93/24148 and WO 97/00697).
  • the present invention concerns the manufacture of the most ambitious multi-valent vaccines to date, the administration of which can prevent or treat infection by Bordetella pertussis, Clostridium tetani, Corynebacterium diphtheriae , Hepatitis B virus, Haemophilus influenzae and N. meningitidis , and preferably also Hepatitis A virus and/or Polio virus, wherein the components of the vaccine do not significantly interfere with the immunological performance of any one component of the vaccine.
  • the present invention provides a multi-valent immunogenic composition for conferring protection in a host against disease caused by Bordetella pertussis, Clostridium tetani, Corynebacterium diphtheriae , Hepatitis B virus, Haemophilus influenzae and N. meningitidis comprising:
  • Hepatitis B surface antigen HepB
  • a carrier protein selected from the group N. meningitidis type A (MenA) and N. meningitidis type C (MenC).
  • TT tetanus toxoid
  • TT is preferably produced by purification of the toxin from a culture of Clostridium tetani followed by chemical detoxification, but is alternatively made by purification of a recombinant, or genetically detoxified analogue of the toxin (for example, as described in EP 209281).
  • Tetanus toxoid also encompasses immunogenic fragments of the fill-length protein (for instance Fragment C—see EP 478602).
  • DT diphtheria toxoid
  • DT is preferably produced by purification of the toxin from a culture of Corynebacterium diphtheriae followed by chemical detoxification, but is alternatively made by purification of a recombinant, or genetically detoxified analogue of the toxin (for example, CRM197, or other mutants as described in U.S. Pat. Nos. 4,709,017, 5,843,711, 5,601,827, and 5,917,017).
  • Acellular pertussis components are well known in the art. Examples include pertussis toxoid (PT), filamentous haemagluttinin (FHA), pertactin (PRN) and agglutinogens 2 and 3. These antigens are partially or highly purified. Preferably 2 or more acellular pertussis components are used in the vaccine. More preferably 2, 3, 4 or all 5 of the above example acellular pertussis components are incorporated in the vaccine. Most preferably PT, FHA and PRN are included. PT may be produced by a variety of manners, for instance by purification of the toxin from a culture of B. pertussis followed by chemical detoxification, or alternatively by purification of a genetically detoxified analogue of PT (for example, as described in U.S. Pat. No. 5,085,862).
  • the bacterial capsular polysaccharide conjugates may comprise any carrier peptide, polypeptide or protein comprising at least one T-helper epitope.
  • the carrier protein(s) used is selected from the group comprising: tetanus toxoid, diphtheria toxoid, CRM197, recombinant diphtheria toxin (as described in any of U.S. Pat. No. 4,709,017, WO 93/25210, WO 95/33481, or WO 00/48638), pneumolysin (preferably chemically detoxified, or a detoxified mutant) from S. pneumoniae , OMPC from N. meningitidis , and protein D (PD) from H.
  • the polysaccharide antigens contained therein are conjugated to more than one carrier.
  • (n ⁇ 1) of the polysaccharides could be carried (separately) on one type of carrier, and 1 on a different carrier, or (n ⁇ 2) on one, and 2 on two different carriers, etc.
  • 1, 2 or all four could be conjugated to different carriers).
  • Protein D is advantageously used as a carrier in the compositions of the invention as it may be used for various (2, 3, 4 or more) polysaccharides in a composition without a marked carrier suppression effect. Most preferably Hib is present as a TT conjugate, and MenA, MenC, MenY and MenW are either TT or PD conjugates. Protein D is also a useful carrier as it provides a further antigen which can provide protection against H influenzae.
  • the polysaccharide may be linked to the carrier protein by any known method (for example, by Likhite, U.S. Pat. No. 4,372,945 and by Armor et al., U.S. Pat. No. 4,474,757).
  • CDAP conjugation is carried out (WO 95/08348).
  • the cyanylating reagent 1-cyano-dimethylaminopyridinium tetrafluoroborate (CDAP) is preferably used for the synthesis of polysaccharide-protein conjugates.
  • the cyanilation reaction can be performed under relatively mild conditions, which avoids hydrolysis of the alkaline sensitive polysaceharides. This synthesis allows direct coupling to a carrier protein.
  • the above immunogenic composition may further comprise one, two, three, four, five, six or seven components selected from the following list: N. meningitidis type Y polysaccharide [MenY] (preferably conjugated), N. meningitidis type W polysaccharide [MenW] (preferably conjugated), the Vi polysaccharide of Salmonella typhi, N. meningitidis (preferably serotype B) outer membrane vesicles, one or more N.
  • N. meningitidis type Y polysaccharide [MenY] preferably conjugated
  • N. meningitidis type W polysaccharide [MenW] preferably conjugated
  • the Vi polysaccharide of Salmonella typhi preferably serotype B
  • N. meningitidis preferably serotype B
  • meningitidis preferably serotype B
  • outer membrane surface-exposed proteins
  • killed attenuated Hepatitis A virus (HepA—preferably the product known as ‘HavrixTM’ [SmithKline Beecham Biologicals]
  • IPV inactivated polio virus
  • types 1, 2 and 3 as is standard in the vaccine art, most preferably the Salk polio vaccine
  • the immunogenic compositions of the invention are preferably formulated as a vaccine for in vivo administration to the host in such a way that the individual components of the composition are formulated such that the immunogenicity of individual components is not substantially impaired by other individual components of the composition.
  • substantially impaired it is meant that upon immunisation, an antibody titre against each component is obtained which is more than 60%, preferably more than 70%, more preferably more than 80%, still more preferably more than 90%, and most preferably more than 95-100% of the titre obtained when the antigen is administered in isolation.
  • the immunogenic compositions of the invention are preferably formulated as a vaccine for in vivo administration to the host, such that they confer an antibody titre superior to the criterion for seroprotection for each antigenic component for an acceptable percentage of human subjects. This is an important test in the assessment of a vaccine's efficacy throughout the population. Antigens with an associated antibody titre above which a host is considered to be seroconverted against the antigen are well known, and such titres are published by organisations such as WHO. Preferably more than 80% of a statistically significant sample of subjects is seroconverted, more preferably more than 90%, still more preferably more than 93% and most preferably 96-100%.
  • the immunogenic composition of the invention are preferably adjuvanted.
  • Suitable adjuvants include an aluminium salt such as aluminium hydroxide gel (alum) or aluminium phosphate, but may also be a salt of calcium, iron or zinc, or may be an insoluble suspension of acylated tyrosine, or acylated sugars, cationically or anionically derivatised polysaccharides, or polyphosphazenes.
  • the adjuvant may also be selected to be a preferential inducer of a TH1 type of response to aid the cell mediated branch of the immune response.
  • Th1-type cytokines tend to favour the induction of cell mediated immune responses to a given antigen, whilst high levels of Th2-type cytokines tend to favour the induction of humoral immune responses to the antigen.
  • Suitable adjuvant systems which promote a predominantly Th1 response include, Monophosphoryl lipid A or a derivative thereof, particularly 3-de-O-acylated monophosphoryl lipid A, and a combination of monophosphoryl lipid A, preferably 3-de-O-acylated monophosphoryl lipid A (3D-MPL) together with an aluminium salt.
  • An enhanced system involves the combination of a monophosphoryl lipid A and a saponin derivative, particularly the combination of QS21 and 3D-MPL as disclosed in WO 94/00153, or a less reactogenic composition where the QS21 is quenched with cholesterol as disclosed in WO 96/33739.
  • a particularly potent adjuvant formulation involving QS21, 3D-MPL and tocopherol in an oil in water emulsion is described in WO 95/17210.
  • the vaccine may additionally comprise a saponin, more preferably QS21.
  • the formulation may also comprises an oil in water emulsion and tocopherol (WO 95/17210).
  • Unmethylated CpG containing oligonucleotides (WO 96/02555) are also preferential inducers of a TH1 response and are suitable for use in the present invention.
  • Aluminium salts are preferred adjuvants in the above immunogenic compositions.
  • HepB should preferably be adsorbed onto aluminium phosphate before admixing with the other components.
  • the polysaccharide conjugates may be unadjuvanted.
  • the present invention also provides a method for producing a vaccine formulation comprising the step of mixing the components of the vaccine together with a pharmaceutically acceptable excipient.
  • a particularly preferred DTPw composition of the invention comprises: TT, DT, Pw, HepB (preferably adsorbed onto aluminium phosphate), Hib (preferably conjugated onto TT and/or unadsorbed), MenA (preferably conjugated onto protein D), and MenC (preferably conjugated onto protein D).
  • the vaccine may be supplied in 2 containers, the first containing DTPw-HepB in a liquid form, and a second containing Hib-MenA-MenC in a lyophilised form. The contents of the containers may be mixed extemporaneously before administering to a host in a single injection.
  • an immunogenic composition or vaccine as herein described for use in a medicament.
  • a method of immunising a human host against disease caused by Bordetella pertussis, Clostridium tetani, Corynebacterium diphtheriae , Hepatitis B virus, Haemophilus influenzae and N. meningitidis which method comprises administering to the host an immunoprotective dose of the immunogenic composition of the invention is also provided.
  • the vaccine preparations of the present invention may be used to protect or treat a mammal susceptible to infection, by means of administering said vaccine via systemic or mucosal route.
  • These administrations may include injection via the intramuscular, intraperitoneal, intradermal or subcutaneous routes; or via mucosal administration to the oral/alimentary, respiratory, genitourinary tracts.
  • each vaccine dose is selected as an amount which induces an immunoprotective response without significant, adverse side effects in typical vaccines. Such amount will vary depending upon which specific immunogen is employed and how it is presented. Generally, it is expected that each dose will comprise 0.1-100 ⁇ g of polysaccharide, preferably 0.1-50 ⁇ g, preferably 0.1-10 ⁇ g, of which 1 to 5 ⁇ g is the most preferable range.
  • the content of protein antigens in the vaccine will typically be in the range 1-100 ⁇ g, preferably 5-50 ⁇ g, most typically in the range 5 -25 ⁇ g.
  • subjects may receive one or several booster immunisations adequately spaced.
  • Vaccine preparation is generally described in Vaccine Design (“The subunit and adjuvant approach” (eds Powell M. F. & Newman M. J.) (1995) Plenum Press New York). Encapsulation within liposomes is described by Fullerton, U.S. Pat. No. 4,235,877.
  • the inventors have also found that for vaccines comprising TT, DT, Pw and Hib, surprisingly a substantially lower dose of Hib can be used in the combination vaccine (compared with the standard dose of 10 ⁇ g per 0.5 mL dose) to obtain at least equivalent antibody titres against the H. influenzae type b capsular polysaccharide antigen. This is contrary to what would have been expected.
  • a multi-valent immunogenic composition comprising killed whole-cell Bordetella pertussis (Pw), tetanus toxoid (TT), diphtheria toxoid (DT), and a conjugate of a carrier protein and the capsular polysaccharide of H. influenzae type B (Hib—preferably conjugated to TT, DT or CRM197), wherein the amount of conjugate per 0.5 mL dose of bulk vaccine is 1-8 ⁇ g, and the immunogenicity of the conjugate is equivalent or improved over such compositions comprising larger amounts of conjugate.
  • Hepatitis B surface antigen may also be included.
  • the amount of conjugate per 0.5 mL dose of bulk vaccine is less than 10 ⁇ g (of polysaccharide in the conjugate), more preferably 1-7 or 2-6 ⁇ g, and most preferably about 2.5, 3, 4 or 5 ⁇ g.
  • the Hib conjugate is not adsorbed onto aluminium adjuvant salt before being mixed with the DTPw vaccine.
  • combination vaccines comprising a Hib conjugate elicits significantly higher anti-Hib antibody titres in a host (compared with a monovalent, unadsorbed Hib conjugate vaccine) if the Hib conjugate is administered in a vaccine additionally comprising 1, but particularly 2 or more additional bacterial polysaccharides and the Hib polysaccharide (and preferably all the polysaccharides) of the vaccine are not adsorbed onto an adjuvant (particularly aluminium salts).
  • a further, independent, aspect of the invention therefore is the provision of a multi-valent immunogenic composition
  • a multi-valent immunogenic composition comprising a conjugate of a carrier protein and the capsular polysaccharide of H. influenzae type B (Hib), wherein said composition additionally comprises 1, but particularly 2 or more further bacterial polysaccharides (preferably more than 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13) capable of conferring protection to a host against infection by the bacteria from which they are derived, and wherein the Hib polysaccharide (and preferably none of said polysaccharides) in the composition are adsorbed onto an aluminium adjuvant salt. Most preferably there is no aluminium adjuvant salt present in the composition.
  • an antigen not being ‘adsorbed onto an aluminium adjuvant salt’ it is meant that an express or dedicated adsorption step for the antigen on fresh aluminium adjuvant salt is not involved in the process of formulating the composition.
  • Hib may be conjugated to any carrier which can provide at least one T-helper epitope (examples of which are described above), and preferably tetanus toxoid.
  • the further bacterial polysaccharides are also conjugated to a carrier protein (examples of which are described above).
  • the capsular polysaccharide of H. influenzae type B and the further polysaccharides are not conjugated to the same carrier (Hib and none of the further polysaccharides share the same carrier), particularly where the carrier is CRM197.
  • at least one of the polysaccharides of the composition is conjugated onto protein D, however this is not essential for the performance of the invention—indeed neither the Hib nor any of the further polysaccharides need be conjugated onto protein D.
  • Hib and further bacterial polysaccharides (and conjugates thereof) are the only antigens present in the composition.
  • the further bacterial polysaccharides are selected from a group consisting of: N. meningitidis serogroup A capsular polysaccharide (MenA), N. meningitidis serogroup C capsular polysaccharide (MenC), N. meningitidis serogroup Y capsular polysaccharide (MenY), N.
  • meningitidis serogroup W capsular polysaccharide MenW
  • Group B Streptococcus group I capsular polysaccharide Group B Streptococcus group II capsular polysaccharide
  • Group B Streptococcus group III capsular polysaccharide Group B Streptococcus group IV capsular polysaccharide
  • Group B Streptococcus group V capsular polysaccharide Staphylococcus aureus type 5 capsular polysaccharide
  • Staphylococcus aureus type 8 capsular polysaccharide Vi polysaccharide from Salmonella typhi, N. meningitidis LPS, M. catarrhalis LPS, and H.
  • LPS lipo-polysaccharide
  • lipo-oligosaccharide lipo-polysaccharide where the lipid A portion has been detoxified by any of a number of known methods (see for example WO 97/18837 or WO 98/33923), or any molecule comprising the O-polysaccharide derived from said LPS.
  • N. meningitidis LPS it is meant one or more of the 12 known immunotypes (L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11 or L12).
  • the amount of PS in each of the above conjugates may be 5 or 10 ⁇ g each per 0.5 mL human dose.
  • the above compositions may also include N. meningitidis serotype B outer membrane vesicles, or one or more N. meningitidis serotype B outer membrane (surface-exposed) proteins, or one or more N. meningitidis LPS (as defined above) to make a global meningitis vaccine.
  • MenA, MenC and MenY are either TT or PD conjugates.
  • the further bacterial polysaccharides may also be selected from any of the capsular pneumococcal polysaccharides (preferably more than 7, more preferably 11 or more, and most preferably 13 or more) such as from serotype: 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F or 33F.
  • the pneumococcal polysaccharides are conjugated (most preferably PD conjugates).
  • pneumococcal polysaccharides derived from at least four serotypes may be selected from the above list. More preferably polysaccharides from more than 7 serotypes are included in the composition, for instance at least 11 serotypes.
  • the composition in one embodiment includes 11 capsular polysaccharides derived from serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (preferably conjugated).
  • polysaccharide antigens preferably conjugated
  • further polysaccharide antigens for example 23 valent (such as serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and 33F), are also contemplated by the invention.
  • serotypes 8 and 12F are advantageously included to form a 13/15 valent vaccine.
  • serotypes 6A and 19A are advantageously included to form a 13 valent vaccine.
  • the pneumococcal polysaccharides may or may not be adsorbed onto aluminium adjuvant salts.
  • GMC post-primary geometric mean concentrations
  • Another indication that no detrimental effect has occurred is if the % of subjects with antibody concentrations of no less than 0.5 ⁇ g/ml differs by no more than 10% (preferably less than 9, 7, 5, 3 or 1%) when comparing 1 month post-primary administrations of the vaccine of the invention versus the vaccine without Hib conjugate.
  • Hib and further bacterial ‘polysaccharides’ the preferred embodiment
  • the invention may be extended to Hib and further bacterial ‘oligosaccharides’ (which naturally have a low number of repeat units, or which are polysaccharides reduced in size for manageability, but are still capable of inducing a protective immune response in a host) which are well known in the vaccine art.
  • the multi-valent immunogenic composition of this aspect of the invention is formulated as a vaccine for in vivo administration to the host wherein the individual components of the composition are formulated such that the immunogenicity of individual components is not impaired by other individual components of the composition (see above definition).
  • the individual components of the composition are formulated such that the immunogenicity of individual components is not impaired by other individual components of the composition (see above definition).
  • no (significantly) detrimental effect occurs to the further bacterial polysaccharides (in terms of protective efficacy) in the combination as compared to their administration in isolation.
  • the multi-valent immunogenic composition of this aspect of the invention is formulated as a vaccine for in vivo administration to the host, which confers an antibody titre superior to the criterion for seroprotection for each antigenic component for an acceptable percentage of human subjects (see above definition).
  • compositions of this aspect of the invention are preferably formulated in a vaccine.
  • the use of the of the multi-valent immunogenic composition of this aspect of the invention in the manufacture of a medicament for the treatment or prevention of diseases caused by infection by Haemophilus influenzae (and preferably also those organisms from which the further bacterial polysaccharides are derived) is also envisioned, as is a method of immunising a human host against disease caused by Haemophilus influenzae (and preferably also those organisms from which the further bacterial polysaccharides are derived), which method comprises administering to the host an immunoprotective dose of the multi-valent immunogenic composition of this aspect of the invention.
  • a process for making the multi-valent immunogenic composition of this aspect of the invention comprising the step of mixing together the individual components. If the further bacterial polysaccharides are to be adsorbed onto an aluminium adjuvant salt, this should be done before Hib is added to the formulation. Preferably an excess of aluminium adjuvant salt should not be used. Most preferably the Hib should be added to the aluminium adjuvanted further polysaccharide extemporanoeusly to the composition being administered to a host.
  • MenAC-Hib N. meningitidis type A capsular polysaccharide conjugated onto protein D (using the CDAP technique), N. meningitidis type C capsular polysaccharide conjugated onto protein D and H. influenzae type b capsular polysaccharide conjugated onto TT were mixed together in an amount of 5 ⁇ g of each polysaccharide in each conjugate per 0.5 mL human dose. The pH was adjusted to 6.1, and was lyophilised in the presence of sucrose.
  • MenC-Hib N. meningitidis type C capsular polysaccharide conjugated onto protein D (using the CDAP technique) and H. influenzae type b capsular polysaccharide conjugated onto TT were mixed together in an amount of 5 ⁇ g of polysaccharide in each conjugate per 0.5 mL human dose. The pH was adjusted to 6.1, and was lyophilised in the presence of sucrose.
  • N. meningitidis type A capsular polysaccharide conjugated onto protein D (using the CDAP techniques), N. meningitidis type C capsular polysaccharide conjugated onto protein D and H. influenzae type b capsular polysaccharide conjugated onto TT were each adsorbed separately in saline onto aluminium phosphate (5 ⁇ g of each conjugate onto 100 ⁇ g, 100 ⁇ g and 60 ⁇ g Al 3+ , respectively, per dose).
  • the adsorbed vaccines were mixed together at a pH of 6.1 and were lyophilised in the presence of sucrose.
  • Study MenAC-Hib 001 evaluates the immunogenicity, reactogenicity and safety induced by MenC-Hib and MenAC-Hib (adsorbed and unadsorbed) made by the above example given as a three-dose primary vaccination in infants.
  • the study was a phase II, randomized study and included five study groups.
  • the formulations that were evaluated were a lyophilized plain and adsorbed formulation of Men AC-Hib and a plain formulation of MenC-Hib. These three formulations were administered to the three first study groups of infants at 3, 4 and 5 months of age; Tritanrix-HepBTM was given concomitantly (as a separate injection) to these three groups.
  • Men AC-Hib The plain formulation of Men AC-Hib was also reconstituted within a liquid diphtheria, tetanus, whole-cell pertussis, hepatitis B combined vaccine (Tritanrix-HepBTM) and administered as a single injection to the fourth study group of infants at 3, 4 and 5 months of age.
  • the fifth group (control) was administered Tritanrix-HepTM-Hib vaccine at 3, 4, 5 months of age.
  • the study was open, but the two first groups receiving the two different formulations of MenAC-Hib were double-blind, as well as the two last groups receiving the Tritanrix-HepBTM-MenAC-Hib and the Tritanrix-HepBTM-Hib vaccines.
  • each formulation that was evaluated induced a good immune response against each antigen (antibodies against meningococcal groups A and C, Poly-Ribosyl-Phosphate (the capsular polysaccharide of H. influenzae type b), Diphtheria toxoid, Tetanus toxoid, Bordetella pertussis and hepatitis B were measured).
  • antigen antigen against meningococcal groups A and C
  • Poly-Ribosyl-Phosphate the capsular polysaccharide of H. influenzae type b
  • Diphtheria toxoid the capsular polysaccharide of H. influenzae type b
  • Tetanus toxoid the capsular polysaccharide of H. influenzae type b
  • Bordetella pertussis Bordetella pertussis and hepatitis B were measured.
  • Each vaccine formulation was well tolerated.
  • This test is an ELISA test that measures IgG content against meningococcal polysaccharide A.
  • FIG. 3 shows the RCC graphs of the data. There is no interference of the MenA polysaccharide antigen to induce at least the same quantity of antibodies when present in a DTPw-HepB/MenAC-Hib vaccine.
  • This test is a bactericidal test that measures the bactericidal antibodies against meningococcus serogroup A. There is no interference of the MenA polysaccharide antigen to induce at least the same quantity of antibodies when present in a DTPw-HepB/MenAC-Hib vaccine.
  • This test is an ELISA test that measures IgG content against meningococcal polysaccharide C.
  • FIG. 4 shows a RCC graph of the data.
  • SBA-MenC is a bactericidal test that measures the bactericidal activity of the serum against meningococcus C. It is a measure of functional antibodies.
  • FIG. 5 shows a RCC graph of the data. There is no interference on the MenC polysaccharide antigen to induce the same quantity of functional antibodies when it is present in a DTPw-HepB/MenAC-Hib vaccine.
  • This test is a bactericidal test that measures the bactericidal antibodies against meningococcus serogroup A. It is a measure of functional antibodies. There is no interference on the MenC polysaccharide antigen to induce the same quantity of functional antibodies when it is present in a DTPw-HepB/MenAC-Hib vaccine. Seroconversion rates of antibodies to diphtheria, tetanus, B.
  • GMT Geometric Mean Titre
  • D T BP HepB MenAC-Hib 2.02 2.18 74.9 357.5 [1.62-2.51] [1.69-2.82] [61.9-90.8] [236.2- 541.2] DTPw-HepB/ 1.69 2.42 71.6 380.2 MenAC-Hib [1.36-2.09] [1.96-3.00] [59.7-85.9] [265.1- 545.2] DTPw-HepB/ 1.26 2.08 69.0 379.1 Hiberix [1.03-1.53] [1.67-2.59] [58.2-81.8] [265.0- 542.2]
  • the pneumococcal vaccine had previously been adsorbed onto 0.5 mg Al 3+ (as AlPO 4 ).
  • Example 4 The vaccine of Example 4 and a control vaccine were administered in a three-dose (3, 4, 5 months of age) schedule to German infants.
  • the immune response results were as follows.
  • Anti pneumococcal IgG antibodies GMC ( ⁇ g/ml) (By Elisa) PS Anti- Group A Group D body Timing N S + [%] GMC N S + [%] GMC Anti-1 PIII 30 100 1.23 33 100 0.99 Anti-3 PIII 30 100 2.04 33 97.0 1.20 Anti-4 PIII 30 100 0.98 33 100 1.03 Anti-5 PIII 30 100 1.33 33 100 1.34 Anti-6B PIII 30 100 0.54 33 100 0.62 Anti-7F PIII 30 100 1.60 33 100 1.33 Anti-9V PIII 30 100 1.61 33 100 1.21 Anti-14 PIII 30 100 2.27 33 100 2.32 Anti-18C PIII 30 100 1.06 33 100 1.04 Anti-19F PIII 30 100 2.05 33 100 1.92 Anti-23F PIII 30 96.7 0.75 33 100 0.76
  • Hiberix (unadsorbed Hib-TT conjugate) has a GMC after a similar administration schedule of about 6 ⁇ g/ml.
  • Group 1 DTPw-HepB extemporaneously mixed with a full dose of Hib-TT (PRP 10 ⁇ g; TT 10-20 ⁇ g; lactose 12.6 ⁇ g; aluminium [as salts] 0.15 mg);
  • Group 2 DTPw-HepB extemporaneously mixed with a half dose of Hib-TT (PRP 5 ⁇ g; TT 10-20 ⁇ g; lactose 10 ⁇ g; aluminium [as salts] 0.0755 mg);
  • Group 3 DTPw-HepB extemporaneously mixed with a quarter dose of Hib-TT (PRP 2.5 ⁇ g; TT 5-10 ⁇ g; lactose 10 ⁇ g; aluminium [as salts] 0.036 mg);
  • Group 4 DTPw-HepB concomitantly administered (in different limbs) with a fill dose of Hib-TT.
  • GTTs Geometric Mean Titers
  • the low dose formulation surprisingly has the highest GMT values. This effect should be even greater if the Hib-TT vaccine is unadsorbed.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Virology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Communicable Diseases (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Oncology (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pulmonology (AREA)
  • Biotechnology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
US10/312,090 2000-06-29 2001-06-27 Multivalent vaccine composition Abandoned US20030180316A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US13/439,829 US9233151B2 (en) 2000-06-29 2012-04-04 Vaccine composition

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
GBGB0015999.6A GB0015999D0 (en) 2000-06-29 2000-06-29 Novel compounds
GB0015999.6 2000-06-29
GB0108363.3 2001-04-03
GB0108364.1 2001-04-03
GBGB0108364.1A GB0108364D0 (en) 2001-04-03 2001-04-03 Vaccine composition
GB0108363A GB0108363D0 (en) 2001-04-03 2001-04-03 Vaccine composition

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US13/439,829 Division US9233151B2 (en) 2000-06-29 2012-04-04 Vaccine composition

Publications (1)

Publication Number Publication Date
US20030180316A1 true US20030180316A1 (en) 2003-09-25

Family

ID=27255788

Family Applications (2)

Application Number Title Priority Date Filing Date
US10/312,090 Abandoned US20030180316A1 (en) 2000-06-29 2001-06-27 Multivalent vaccine composition
US13/439,829 Expired - Fee Related US9233151B2 (en) 2000-06-29 2012-04-04 Vaccine composition

Family Applications After (1)

Application Number Title Priority Date Filing Date
US13/439,829 Expired - Fee Related US9233151B2 (en) 2000-06-29 2012-04-04 Vaccine composition

Country Status (35)

Country Link
US (2) US20030180316A1 (fr)
EP (4) EP1296715B2 (fr)
JP (2) JP4870895B2 (fr)
KR (3) KR100837917B1 (fr)
CN (2) CN101708333B (fr)
AP (1) AP1695A (fr)
AT (1) ATE534402T1 (fr)
AU (2) AU2001281895C1 (fr)
BG (2) BG66238B1 (fr)
BR (2) BRPI0112057B8 (fr)
CA (2) CA2783274C (fr)
CY (2) CY1112280T1 (fr)
CZ (1) CZ20024224A3 (fr)
DK (2) DK1946769T3 (fr)
DZ (1) DZ3399A1 (fr)
EA (2) EA006313B1 (fr)
EG (1) EG24742A (fr)
ES (2) ES2375704T5 (fr)
HK (1) HK1055244A1 (fr)
HU (3) HU227893B1 (fr)
IL (2) IL153506A0 (fr)
MA (1) MA25824A1 (fr)
MX (1) MXPA03000198A (fr)
MY (1) MY133981A (fr)
NO (1) NO332495B1 (fr)
NZ (1) NZ523319A (fr)
OA (1) OA12302A (fr)
PE (1) PE20020126A1 (fr)
PL (2) PL210015B1 (fr)
PT (2) PT1946769E (fr)
SI (2) SI1946769T1 (fr)
SK (1) SK288007B6 (fr)
UA (2) UA76952C2 (fr)
UY (1) UY26801A1 (fr)
WO (1) WO2002000249A2 (fr)

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005089794A3 (fr) * 2004-03-15 2006-03-09 Chiron Srl Vaccins de combinaison a faible dose de conjugue h.influenza type b
US20060127414A1 (en) * 2002-11-01 2006-06-15 Glaxosmithkline Biologicals S.A. Immunogenic Composition
US20070184071A1 (en) * 2005-04-08 2007-08-09 Wyeth Multivalent pneumococcal polysaccharide-protein conjugate composition
US20070231340A1 (en) * 2005-04-08 2007-10-04 Wyeth Multivalent pneumococcal polysaccharide-protein conjugate composition
US20080193476A1 (en) * 2005-06-27 2008-08-14 Ralph Leon Biemans Immunogenic Composition
US20090130137A1 (en) * 2005-04-08 2009-05-21 Wyeth Multivalent pneumococcal polysaccharide-protein conjugate composition
US20090214586A1 (en) * 2005-03-17 2009-08-27 Mario Contorni Combination Vaccines With Whole Cell Pertussis Antigen
US20090318382A1 (en) * 2006-06-30 2009-12-24 Institut Pasteur Use of bacterial polysaccharides for biofilm inhibition
US20100034847A1 (en) * 2005-09-01 2010-02-11 Astrid Borkowski Multiple vaccination including Serogroup C Meningococcus
US20100034850A1 (en) * 2006-09-07 2010-02-11 Herve De Hemptinne Vaccine
US20110071279A1 (en) * 2005-04-08 2011-03-24 Wyeth Multivalent pneumococcal polysaccharide-protein conjugate composition
US20110182942A1 (en) * 2008-05-30 2011-07-28 Wendell David Zollinger Meningococcal multivalent native outer membrane vesicle vaccine, methods of making and use thereof
US20110195086A1 (en) * 2010-02-09 2011-08-11 Caulfield Michael J 15-valent pneumococcal polysaccharide-protein conjugate vaccine composition
US8808707B1 (en) 2006-05-08 2014-08-19 Wyeth Llc Pneumococcal dosing regimen
US20180099039A1 (en) * 2014-01-21 2018-04-12 Pfizer Inc. Immunogenic Compositions Comprising Conjugated Capsular Saccharide Antigens and Uses Thereof
CN111821432A (zh) * 2020-08-05 2020-10-27 北京智飞绿竹生物制药有限公司 一种多价肺炎球菌结合疫苗
US11116828B2 (en) 2017-12-06 2021-09-14 Merck Sharp & Dohme Corp. Compositions comprising Streptococcus pneumoniae polysaccharide-protein conjugates and methods of use thereof
US11642406B2 (en) 2018-12-19 2023-05-09 Merck Sharp & Dohme Llc Compositions comprising Streptococcus pneumoniae polysaccharide-protein conjugates and methods of use thereof

Families Citing this family (75)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4540795B2 (ja) * 2000-03-10 2010-09-08 一般財団法人阪大微生物病研究会 生ワクチンの細胞性免疫活性を不活化ワクチンにも起こさせる方法、及びこれより得られる混合ワクチン
GB0108364D0 (en) * 2001-04-03 2001-05-23 Glaxosmithkline Biolog Sa Vaccine composition
CZ20024224A3 (cs) 2000-06-29 2003-05-14 Glaxosmithkline Biologicals S. A. Farmaceutický prostředek
HU230490B1 (hu) 2001-01-23 2016-08-29 Sanofi Pasteur Inc. Multivalens, meningokokkusz-eredetű poliszaccharid és fehérje konjugátumát tartalmazó vakcina
AU2007200116A1 (en) * 2001-04-03 2007-02-01 Glaxosmithkline Biologicals S.A. Vaccine composition
WO2002099035A2 (fr) 2001-05-31 2002-12-12 Chiron Corporation Particules de replicon d'alphavirus chimerique
GB0115176D0 (en) 2001-06-20 2001-08-15 Chiron Spa Capular polysaccharide solubilisation and combination vaccines
GB0302218D0 (en) 2003-01-30 2003-03-05 Chiron Sri Vaccine formulation & Mucosal delivery
BR0310042A (pt) * 2002-05-14 2005-04-05 Chiron Srl Vacinas de combinação mucosal para meningite bacteriana
DE60328481D1 (de) 2002-05-14 2009-09-03 Novartis Vaccines & Diagnostic Schleimhautapplizierter impfstoff, der das adjuvanz chitosan und menigokokkenantigene enthält
HUE031886T2 (en) 2002-10-11 2017-08-28 Glaxosmithkline Biologicals Sa Polypeptide vaccines for extensive protection against hypervirulent meningococcal lines
GB0227346D0 (en) 2002-11-22 2002-12-31 Chiron Spa 741
JP2006516609A (ja) * 2003-01-30 2006-07-06 カイロン ソチエタ ア レスポンサビリタ リミタータ 粘膜髄膜炎菌性ワクチン
CA2514328C (fr) * 2003-01-30 2020-01-14 Chiron Srl Vaccins injectables contre les multiples serogroupes du meningocoque
JP2007516219A (ja) 2003-05-07 2007-06-21 アヴェンティス パストゥール インコーポレイテッド 髄膜炎菌ワクチン接種に対する免疫原性の増強の方法
GB0313916D0 (en) 2003-06-16 2003-07-23 Glaxosmithkline Biolog Sa Vaccine composition
WO2005000345A2 (fr) * 2003-06-23 2005-01-06 Aventis Pasteur, Inc. Procede d'immunisation contre la bacterie neisseria meningitidis serogroupes a et c
GB0323103D0 (en) 2003-10-02 2003-11-05 Chiron Srl De-acetylated saccharides
EP1670506B1 (fr) * 2003-10-02 2012-11-21 Novartis AG Vaccins liquides contre de multiples serogroupes meningococciques
CU23404A1 (es) * 2003-11-19 2009-08-04 Ct Ingenieria Genetica Biotech Polisacáridos capsulares de neisseria meningitidis como inmunopotenciadores mucosales y formulaciones resultantes
GB0500787D0 (en) 2005-01-14 2005-02-23 Chiron Srl Integration of meningococcal conjugate vaccination
GB0409745D0 (en) 2004-04-30 2004-06-09 Chiron Srl Compositions including unconjugated carrier proteins
EP1740217B1 (fr) 2004-04-30 2011-06-15 Novartis Vaccines and Diagnostics S.r.l. Integration d'une vaccination conjuguee antimeningococcique
GB0502096D0 (en) 2005-02-01 2005-03-09 Chiron Srl Purification of streptococcal capsular polysaccharide
US8119146B2 (en) 2005-04-18 2012-02-21 Angelica Medina-Selby Expressing hepatitis B virus surface antigen for vaccine preparation
GB0513069D0 (en) * 2005-06-27 2005-08-03 Glaxosmithkline Biolog Sa Immunogenic composition
CN1709505B (zh) * 2005-07-13 2010-06-16 北京绿竹生物制药有限公司 多价细菌荚膜多糖-蛋白质结合物联合疫苗
WO2007047749A1 (fr) 2005-10-18 2007-04-26 Novartis Vaccines And Diagnostics Inc. Immunisations mucosiques et systemiques avec particules de replicon d’alphavirus
GB0522765D0 (en) 2005-11-08 2005-12-14 Chiron Srl Combination vaccine manufacture
GB0524066D0 (en) 2005-11-25 2006-01-04 Chiron Srl 741 ii
GB0607088D0 (en) * 2006-04-07 2006-05-17 Glaxosmithkline Biolog Sa Vaccine
EP3020411A1 (fr) * 2005-12-22 2016-05-18 GlaxoSmithKline Biologicals s.a. Vaccin
EA200801368A1 (ru) * 2005-12-23 2008-12-30 Глаксосмитклайн Байолоджикалс С.А. Конъюгатные вакцины
UA92782C2 (ru) * 2006-01-17 2010-12-10 Арне Форсгрен Новый поверхностный белок haemophilus influenzae (белок е; ре)
AU2007229449A1 (en) 2006-03-22 2007-10-04 Novartis Ag Regimens for immunisation with meningococcal conjugates
TW200806315A (en) * 2006-04-26 2008-02-01 Wyeth Corp Novel formulations which stabilize and inhibit precipitation of immunogenic compositions
EA201490303A1 (ru) 2007-05-02 2014-05-30 Глаксосмитклайн Байолоджикалс С.А. Вакцина
CA2688268A1 (fr) 2007-06-04 2008-12-11 Novartis Ag Formulation de vaccins contre la meningite
PT2167121E (pt) 2007-06-26 2015-12-02 Glaxosmithkline Biolog Sa Vacina compreendendo conjugados de polissacáridos capsulares de streptococcus pneumoniae
GB0818453D0 (en) 2008-10-08 2008-11-12 Novartis Ag Fermentation processes for cultivating streptococci and purification processes for obtaining cps therefrom
PE20100365A1 (es) * 2008-10-24 2010-05-21 Panacea Biotec Ltd Novedosas vacunas de combinacion con tos ferina de celulas enteras y metodo para su elaboracion
GB0822634D0 (en) 2008-12-11 2009-01-21 Novartis Ag Meningitis vaccines
GB0822633D0 (en) 2008-12-11 2009-01-21 Novartis Ag Formulation
EP3170508B1 (fr) * 2010-06-04 2019-11-13 Wyeth LLC Formulations vaccinales
SI2651436T1 (sl) 2010-12-14 2016-07-29 Glaxosmithkline Biologicals S.A. Mikrobakterijski antigenski sestavek
US10092640B2 (en) 2011-01-05 2018-10-09 Bharat Biotech International Limited Combination heptavalent vaccine
GB201105981D0 (en) 2011-04-08 2011-05-18 Glaxosmithkline Biolog Sa Novel process
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
GB2495341B (en) 2011-11-11 2013-09-18 Novartis Ag Fermentation methods and their products
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
CN104302315B (zh) * 2012-01-30 2018-02-06 印度血清研究所私人有限公司 免疫原性组合物及其制备方法
WO2013132043A1 (fr) * 2012-03-08 2013-09-12 Novartis Ag Vaccins combinés comprenant des agonistes du tlr4
US20140037680A1 (en) 2012-08-06 2014-02-06 Glaxosmithkline Biologicals, S.A. Novel method
JP2015525794A (ja) 2012-08-06 2015-09-07 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 乳児においてｒｓｖ及び百日咳菌に対する免疫応答を惹起するための方法
RU2015111987A (ru) 2012-10-12 2016-12-10 Глаксосмитклайн Байолоджикалс Са Несшитые бесклеточные коклюшные антигены для применения в комбинированных вакцинах
WO2014060383A1 (fr) * 2012-10-17 2014-04-24 Glaxosmithkline Biologicals S.A. Composition immunogène comprenant un ou plusieurs conjugués saccharides capsulaires de streptococcus pneumoniae et un constituant protéique comprenant la protéine e et/ou pila d'haemophilus influenzae
KR20140075201A (ko) * 2012-12-11 2014-06-19 에스케이케미칼주식회사 다가 폐렴구균 다당류-단백질 접합체 조성물
US8916173B2 (en) 2013-03-08 2014-12-23 Crucell Holland B.V. Acellular pertussis vaccine
EP3019513B1 (fr) * 2013-07-07 2018-01-17 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Vaccins synthétiques contre le streptococcus pneumoniae type 1
CN105555304A (zh) 2013-08-05 2016-05-04 葛兰素史密丝克莱恩生物有限公司 联合免疫原性组合物
US9815886B2 (en) 2014-10-28 2017-11-14 Adma Biologics, Inc. Compositions and methods for the treatment of immunodeficiency
RU2626532C2 (ru) * 2015-01-16 2017-07-28 Федеральное государственное унитарное предприятие "Научно-производственное объединение по медицинским иммунобиологическим препаратам "Микроген" Министерства здравоохранения Российской Федерации Комбинированная вакцина для профилактики коклюша, дифтерии, столбняка, гепатита в и инфекции, вызываемой haemophilus influenzae тип в
RU2723045C2 (ru) * 2015-02-19 2020-06-08 Пфайзер Инк. Композиции neisseria meningitidis и способы их получения
TWI789357B (zh) 2016-08-05 2023-01-11 南韓商Ｓｋ生物科技股份有限公司 多價肺炎球菌多醣-蛋白質共軛物組成物(二)
CA3031797A1 (fr) 2016-08-05 2018-02-08 Sanofi Pasteur, Inc. Composition d'un conjugue polysaccharide-proteine pneumococcique multivalent
EP4309670A3 (fr) 2016-09-02 2024-07-17 Sanofi Pasteur, Inc. Vaccin contre neisseria meningitidis
US10259865B2 (en) 2017-03-15 2019-04-16 Adma Biologics, Inc. Anti-pneumococcal hyperimmune globulin for the treatment and prevention of pneumococcal infection
JP6950099B2 (ja) 2018-02-05 2021-10-13 サノフィ パスツール インコーポレイティッド 多価肺炎球菌多糖体−タンパク質複合体組成物
BR112020014978A2 (pt) 2018-02-05 2020-12-22 Sanofi Pasteur, Inc. Composição de conjugado polissacarídeo-proteína pneumocócico multivalente
BR112020021296A2 (pt) 2018-04-18 2021-01-26 Sk Bioscience Co., Ltd. polissacarídeo capsular de streptococcus pneumoniae e conjugado imunogênico do mesmo
US11896656B2 (en) * 2018-04-30 2024-02-13 Merck Sharp & Dohme Llc Methods for providing a homogenous solution of lyophilized mutant diptheria toxin in dimethylsulfoxide
KR20200005458A (ko) 2018-07-06 2020-01-15 주식회사 유바이오로직스 다가 폐렴구균 다당체-단백질 접합체를 포함하는 면역원성 조성물, 및 이를 포함하는 약학 조성물
US20210401960A1 (en) * 2018-11-10 2021-12-30 Bharat Biotech International Limited Multivalent glycoconjugates immunogenic compositions
CA3141460A1 (fr) 2019-05-20 2020-11-26 Soligenix, Inc. Compositions et procedes de fabrication de vaccins anti-filovirus trivalents

Citations (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4057685A (en) * 1972-02-02 1977-11-08 Abbott Laboratories Chemically modified endotoxin immunizing agent
US4235877A (en) * 1979-06-27 1980-11-25 Merck & Co., Inc. Liposome particle containing viral or bacterial antigenic subunit
US4365170A (en) * 1979-09-21 1982-12-21 Hitachi, Ltd. Semiconductor switch
US4459286A (en) * 1983-01-31 1984-07-10 Merck & Co., Inc. Coupled H. influenzae type B vaccine
US4650740A (en) * 1983-09-13 1987-03-17 Fuji Photo Film Co., Ltd. Heat-sensitive recording material
US4673574A (en) * 1981-08-31 1987-06-16 Anderson Porter W Immunogenic conjugates
US4709017A (en) * 1985-06-07 1987-11-24 President And Fellows Of Harvard College Modified toxic vaccines
US4808700A (en) * 1984-07-09 1989-02-28 Praxis Biologics, Inc. Immunogenic conjugates of non-toxic E. coli LT-B enterotoxin subunit and capsular polymers
US5651971A (en) * 1993-09-22 1997-07-29 Henry M. Jackson Foundation For The Advancement Of Military Medicine Producing immunogenic constructs using soluble carbohydrates activated via organic cyanylating reagents
US5843711A (en) * 1992-05-06 1998-12-01 The Regents Of The University Of California Diphtheria toxin receptor-binding region
US5849301A (en) * 1993-09-22 1998-12-15 Henry M. Jackson Foundation For The Advancement Of Military Medicine Producing immunogenic constructs using soluable carbohydrates activated via organic cyanylating reagents
US5869058A (en) * 1994-05-25 1999-02-09 Yeda Research And Development Co. Ltd. Peptides used as carriers in immunogenic constructs suitable for development of synthetic vaccines
US5917017A (en) * 1994-06-08 1999-06-29 President And Fellows Of Harvard College Diphtheria toxin vaccines bearing a mutated R domain
US5965714A (en) * 1997-10-02 1999-10-12 Connaught Laboratories, Inc. Method for the covalent attachment of polysaccharides to protein molecules
US6146902A (en) * 1998-12-29 2000-11-14 Aventis Pasteur, Inc. Purification of polysaccharide-protein conjugate vaccines by ultrafiltration with ammonium sulfate solutions
US6251401B1 (en) * 1994-11-02 2001-06-26 Chiron S.P.A. Combined meningitis vaccine
US6455673B1 (en) * 1994-06-08 2002-09-24 President And Fellows Of Harvard College Multi-mutant diphtheria toxin vaccines
US20030099672A1 (en) * 2000-03-17 2003-05-29 Dominique Schultz Pneumococcus polysaccharide conjugates for use as vaccine against tetanus an diphtheria
US20040096461A1 (en) * 2002-07-30 2004-05-20 Baxter Healthcare Corporation Chimeric multivalent polysaccharide conjugate vaccines
US20040202668A1 (en) * 2001-04-03 2004-10-14 Dominique Boutriau Vaccine composition
US20080199490A1 (en) * 2005-06-27 2008-08-21 Glaxosmithkline Biologicals S.A. Immunogenic Composition
US20080260773A1 (en) * 2004-12-24 2008-10-23 Giuseppe Del Giudice Saccharide Conjugate Vaccines
US20080305127A1 (en) * 2005-12-23 2008-12-11 Glaxosmithkline Biologicals S.A. Conjugate Vaccines
US20090010959A1 (en) * 2005-12-22 2009-01-08 Ralph Leon Biemans Pneumococcal Polysaccharide Conjugate Vaccine
US20090043077A1 (en) * 2005-02-01 2009-02-12 Francesco Berti Conjugation of streptococcal capsular saccharides
US20090162394A1 (en) * 2006-04-07 2009-06-25 Ralph Leon Biemans Vaccine
US20090311285A1 (en) * 2007-01-04 2009-12-17 Glaxosmith Kline Biologicals S.A. A Corporation Vaccine
US20100060945A1 (en) * 2007-03-14 2010-03-11 Konica Minolta Business Technologies, Inc. Information embedding method, its program and information embedding device
US20100074918A1 (en) * 2007-05-02 2010-03-25 Jan Poolman Vaccine
US20100104593A1 (en) * 2005-01-14 2010-04-29 Chiron Srl Meningococcal conjugate vaccination
US20100143399A1 (en) * 2007-01-04 2010-06-10 Glaxosmithkline Biologicals Process for manufacturing vaccines
US20100183662A1 (en) * 2007-06-26 2010-07-22 Ralph Leon Biemans Vaccine comprising streptococcus pneumoniae capsular polysaccharide conjugates
US20100203137A1 (en) * 2007-06-04 2010-08-12 Mario Contorni Formulation of meningitis vaccines

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4372945A (en) 1979-11-13 1983-02-08 Likhite Vilas V Antigen compounds
IL61904A (en) 1981-01-13 1985-07-31 Yeda Res & Dev Synthetic vaccine against influenza virus infections comprising a synthetic peptide and process for producing same
GB8516442D0 (en) 1985-06-28 1985-07-31 Wellcome Found Cloned antigen
GB8727489D0 (en) 1987-11-24 1987-12-23 Connaught Lab Detoxification of pertussis toxin
GB8914122D0 (en) 1989-06-20 1989-08-09 Wellcome Found Polypeptide expression
SE466259B (sv) 1990-05-31 1992-01-20 Arne Forsgren Protein d - ett igd-bindande protein fraan haemophilus influenzae, samt anvaendning av detta foer analys, vacciner och uppreningsaendamaal
CA2059692C (fr) * 1991-01-28 2004-11-16 Peter J. Kniskern Vaccin conjugue de polysaccharide contre les pneumocoques
UA40596C2 (uk) 1992-05-23 2001-08-15 Смітклайн Бічем Байолоджікалс С.А. Композиція вакцини та спосіб її одержання
ATE188508T1 (de) 1992-06-18 2000-01-15 Harvard College Impfstoffe gegen diphtherietoxin
NZ253137A (en) 1992-06-25 1996-08-27 Smithkline Beecham Biolog Vaccine comprising antigen and/or antigenic composition, qs21 (quillaja saponaria molina extract) and 3 de-o-acylated monophosphoryl lipid a.
DE69323264D1 (de) * 1992-10-27 1999-03-11 American Cyanamid Co Pädiatrische Kombinationsvakzine mit verbesserter Immunogenizität jeder Vakzine komponente
GB9326253D0 (en) 1993-12-23 1994-02-23 Smithkline Beecham Biolog Vaccines
DK0772619T4 (da) 1994-07-15 2011-02-21 Univ Iowa Res Found Immunmodulatoriske oligonukleotider
UA56132C2 (uk) 1995-04-25 2003-05-15 Смітклайн Бічем Байолоджікалс С.А. Композиція вакцини (варіанти), спосіб стабілізації qs21 відносно гідролізу (варіанти), спосіб приготування композиції вакцини
DK1082965T3 (da) * 1995-06-23 2009-07-27 Glaxosmithkline Biolog Sa Et vaccinepræparat der omfatter et polysaccharidkonjugatantigen adsorberet på aluminiumphosphat
US5997881A (en) 1995-11-22 1999-12-07 University Of Maryland, Baltimore Method of making non-pyrogenic lipopolysaccharide or A
WO1998033923A1 (fr) 1997-01-30 1998-08-06 Imperial College Of Science, Technology & Medicine GENES MUTANTS msbB ou $i(htrB)
DE69735191T2 (de) * 1997-09-15 2006-10-05 Sanofi Pasteur Msd Verfahren zur Herstellung multivalenter Impfstoffe
US7018637B2 (en) * 1998-02-23 2006-03-28 Aventis Pasteur, Inc Multi-oligosaccharide glycoconjugate bacterial meningitis vaccines
GB9806456D0 (en) * 1998-03-25 1998-05-27 Smithkline Beecham Biolog Vaccine composition
GB9925559D0 (en) * 1999-10-28 1999-12-29 Smithkline Beecham Biolog Novel method
CZ20024224A3 (cs) 2000-06-29 2003-05-14 Glaxosmithkline Biologicals S. A. Farmaceutický prostředek
GB0405787D0 (en) * 2004-03-15 2004-04-21 Chiron Srl Low dose vaccines

Patent Citations (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4057685A (en) * 1972-02-02 1977-11-08 Abbott Laboratories Chemically modified endotoxin immunizing agent
US4235877A (en) * 1979-06-27 1980-11-25 Merck & Co., Inc. Liposome particle containing viral or bacterial antigenic subunit
US4365170A (en) * 1979-09-21 1982-12-21 Hitachi, Ltd. Semiconductor switch
US4673574A (en) * 1981-08-31 1987-06-16 Anderson Porter W Immunogenic conjugates
US4459286A (en) * 1983-01-31 1984-07-10 Merck & Co., Inc. Coupled H. influenzae type B vaccine
US4650740A (en) * 1983-09-13 1987-03-17 Fuji Photo Film Co., Ltd. Heat-sensitive recording material
US4808700A (en) * 1984-07-09 1989-02-28 Praxis Biologics, Inc. Immunogenic conjugates of non-toxic E. coli LT-B enterotoxin subunit and capsular polymers
US4709017A (en) * 1985-06-07 1987-11-24 President And Fellows Of Harvard College Modified toxic vaccines
US5843711A (en) * 1992-05-06 1998-12-01 The Regents Of The University Of California Diphtheria toxin receptor-binding region
US5651971A (en) * 1993-09-22 1997-07-29 Henry M. Jackson Foundation For The Advancement Of Military Medicine Producing immunogenic constructs using soluble carbohydrates activated via organic cyanylating reagents
US5849301A (en) * 1993-09-22 1998-12-15 Henry M. Jackson Foundation For The Advancement Of Military Medicine Producing immunogenic constructs using soluable carbohydrates activated via organic cyanylating reagents
US5869058A (en) * 1994-05-25 1999-02-09 Yeda Research And Development Co. Ltd. Peptides used as carriers in immunogenic constructs suitable for development of synthetic vaccines
US5917017A (en) * 1994-06-08 1999-06-29 President And Fellows Of Harvard College Diphtheria toxin vaccines bearing a mutated R domain
US6455673B1 (en) * 1994-06-08 2002-09-24 President And Fellows Of Harvard College Multi-mutant diphtheria toxin vaccines
US6251401B1 (en) * 1994-11-02 2001-06-26 Chiron S.P.A. Combined meningitis vaccine
US5965714A (en) * 1997-10-02 1999-10-12 Connaught Laboratories, Inc. Method for the covalent attachment of polysaccharides to protein molecules
US6146902A (en) * 1998-12-29 2000-11-14 Aventis Pasteur, Inc. Purification of polysaccharide-protein conjugate vaccines by ultrafiltration with ammonium sulfate solutions
US20030099672A1 (en) * 2000-03-17 2003-05-29 Dominique Schultz Pneumococcus polysaccharide conjugates for use as vaccine against tetanus an diphtheria
US20040202668A1 (en) * 2001-04-03 2004-10-14 Dominique Boutriau Vaccine composition
US20040096461A1 (en) * 2002-07-30 2004-05-20 Baxter Healthcare Corporation Chimeric multivalent polysaccharide conjugate vaccines
US20080260773A1 (en) * 2004-12-24 2008-10-23 Giuseppe Del Giudice Saccharide Conjugate Vaccines
US20100104593A1 (en) * 2005-01-14 2010-04-29 Chiron Srl Meningococcal conjugate vaccination
US20090043077A1 (en) * 2005-02-01 2009-02-12 Francesco Berti Conjugation of streptococcal capsular saccharides
US20090136541A1 (en) * 2005-06-27 2009-05-28 Ralph Leon Biemans Immunogenic composition
US20080199490A1 (en) * 2005-06-27 2008-08-21 Glaxosmithkline Biologicals S.A. Immunogenic Composition
US20090252759A1 (en) * 2005-06-27 2009-10-08 Ralph Leon Biemans Immunogenic composition
US20100215686A1 (en) * 2005-06-27 2010-08-26 Ralph Leon Biemans Process for Manufacturing Vaccines
US20090010959A1 (en) * 2005-12-22 2009-01-08 Ralph Leon Biemans Pneumococcal Polysaccharide Conjugate Vaccine
US20090017059A1 (en) * 2005-12-22 2009-01-15 Glaxosmithkline Biologicals S.A. Vaccine Comprising Streptococcus Pneumoniae Capsular Polysaccharide Conjugates
US20090017072A1 (en) * 2005-12-22 2009-01-15 Glaxosmithkline Biologicals S.A. Vaccine
US20080305127A1 (en) * 2005-12-23 2008-12-11 Glaxosmithkline Biologicals S.A. Conjugate Vaccines
US20090162394A1 (en) * 2006-04-07 2009-06-25 Ralph Leon Biemans Vaccine
US20100143399A1 (en) * 2007-01-04 2010-06-10 Glaxosmithkline Biologicals Process for manufacturing vaccines
US20090311285A1 (en) * 2007-01-04 2009-12-17 Glaxosmith Kline Biologicals S.A. A Corporation Vaccine
US20100060945A1 (en) * 2007-03-14 2010-03-11 Konica Minolta Business Technologies, Inc. Information embedding method, its program and information embedding device
US20100074918A1 (en) * 2007-05-02 2010-03-25 Jan Poolman Vaccine
US20100203137A1 (en) * 2007-06-04 2010-08-12 Mario Contorni Formulation of meningitis vaccines
US20100183662A1 (en) * 2007-06-26 2010-07-22 Ralph Leon Biemans Vaccine comprising streptococcus pneumoniae capsular polysaccharide conjugates
US20100209450A1 (en) * 2007-06-26 2010-08-19 Ralph Leon Biemans Vaccine comprising streptococcus pneumoniae capsular polysaccharide conjugates

Cited By (72)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8409587B2 (en) * 2002-11-01 2013-04-02 Glaxosmithkline Biologicals S.A. Immunogenic composition
US20060127414A1 (en) * 2002-11-01 2006-06-15 Glaxosmithkline Biologicals S.A. Immunogenic Composition
WO2005089794A3 (fr) * 2004-03-15 2006-03-09 Chiron Srl Vaccins de combinaison a faible dose de conjugue h.influenza type b
US20090208526A1 (en) * 2004-03-15 2009-08-20 Mario Contorni Combination vaccines with low dose of hib conjugate
US9259460B2 (en) 2004-03-15 2016-02-16 Glaxosmithkline Biologicals Sa Combination vaccines with low dose of Hib conjugate
US20090214586A1 (en) * 2005-03-17 2009-08-27 Mario Contorni Combination Vaccines With Whole Cell Pertussis Antigen
US8883166B2 (en) * 2005-03-17 2014-11-11 Novartis Ag Combination vaccines with whole cell pertussis antigen
US8895024B2 (en) 2005-04-08 2014-11-25 Wyeth Llc Multivalent pneumococcal polysaccharide-protein conjugate composition
US7709001B2 (en) 2005-04-08 2010-05-04 Wyeth Llc Multivalent pneumococcal polysaccharide-protein conjugate composition
US9480736B2 (en) 2005-04-08 2016-11-01 Wyeth Llc Multivalent pneumococcal polysaccharide-protein conjugate composition
US9981045B2 (en) 2005-04-08 2018-05-29 Wyeth Llc Multivalent pneumococcal polysaccharide-protein conjugate composition
US8895724B2 (en) 2005-04-08 2014-11-25 Wyeth Llc Multivalent pneumococcal polysaccharide-protein conjugate composition
US11969474B2 (en) 2005-04-08 2024-04-30 Wyeth Llc Multivalent pneumococcal polysaccharide-protein conjugate composition
US20070231340A1 (en) * 2005-04-08 2007-10-04 Wyeth Multivalent pneumococcal polysaccharide-protein conjugate composition
US11191830B2 (en) 2005-04-08 2021-12-07 Wyeth Llc Process for preparing pneumococcal polysaccharide-protein conjugates
US10780160B2 (en) 2005-04-08 2020-09-22 Wyeth Llc Process for preparing pneumococcal polysaccharide-protein conjugates
US8603484B2 (en) 2005-04-08 2013-12-10 Wyeth Llc Multivalent pneumococcal polysaccharide-protein conjugate composition
US20100316666A1 (en) * 2005-04-08 2010-12-16 Wyeth Multivalent Pneumococcal Polysaccharide-Protein Conjugate Composition
US20110071279A1 (en) * 2005-04-08 2011-03-24 Wyeth Multivalent pneumococcal polysaccharide-protein conjugate composition
US7955605B2 (en) * 2005-04-08 2011-06-07 Wyeth Llc Multivalent pneumococcal polysaccharide-protein conjugate composition
US20070184071A1 (en) * 2005-04-08 2007-08-09 Wyeth Multivalent pneumococcal polysaccharide-protein conjugate composition
US10716848B2 (en) 2005-04-08 2020-07-21 Wyeth Llc Process for preparing pneumococcal polysaccharide-protein conjugates
US20110201791A1 (en) * 2005-04-08 2011-08-18 Wyeth Llc Multivalent pneumococcal polysaccharide-protein conjugate composition
US20090130137A1 (en) * 2005-04-08 2009-05-21 Wyeth Multivalent pneumococcal polysaccharide-protein conjugate composition
US9399060B2 (en) 2005-04-08 2016-07-26 Wyeth Llc Multivalent pneumococcal polysaccharide-protein conjugate composition
US8808708B2 (en) 2005-04-08 2014-08-19 Wyeth Llc Multivalent pneumococcal polysaccharide-protein conjugate composition
US9981035B2 (en) 2005-04-08 2018-05-29 Wyeth Llc Process for preparing pneumococcal polysaccharide-protein conjugates
US10245317B2 (en) 2005-06-27 2019-04-02 Glaxosmithkline Biologicals S.A. Immunogenic composition
US8431136B2 (en) 2005-06-27 2013-04-30 Glaxosmithkline Biologicals S.A. Immunogenic composition
US10166287B2 (en) 2005-06-27 2019-01-01 Glaxosmithkline Biologicals S.A. Immunogenic composition
US20080193476A1 (en) * 2005-06-27 2008-08-14 Ralph Leon Biemans Immunogenic Composition
US8398983B2 (en) 2005-06-27 2013-03-19 Glaxosmithkline Biologicals, S.A. Immunogenic composition
US9358279B2 (en) 2005-06-27 2016-06-07 Glaxosmithkline Biologicals S.A. Immunogenic composition
US20080199490A1 (en) * 2005-06-27 2008-08-21 Glaxosmithkline Biologicals S.A. Immunogenic Composition
US8883163B2 (en) 2005-06-27 2014-11-11 Glaxosmithkline Biologicals S.A. Immunogenic composition
US20200000911A1 (en) * 2005-06-27 2020-01-02 Glaxosmithkline Biologicals S.A. Immunogenic composition
US11241495B2 (en) 2005-06-27 2022-02-08 Glaxosmithkline Biologicals S.A. Immunogenic composition
US20090252759A1 (en) * 2005-06-27 2009-10-08 Ralph Leon Biemans Immunogenic composition
US20090136541A1 (en) * 2005-06-27 2009-05-28 Ralph Leon Biemans Immunogenic composition
US9931397B2 (en) 2005-06-27 2018-04-03 Glaxosmithkline Biologicals S.A. Immunogenic composition
US9789179B2 (en) 2005-06-27 2017-10-17 Glaxosmithkline Biologicals S.A. Immunogenic composition
US9486515B2 (en) 2005-06-27 2016-11-08 Glaxosmithkline Biologicals S.A. Immunogenic composition
US20090041802A1 (en) * 2005-06-27 2009-02-12 Ralph Leon Biemans Immunogenic composition
US8361477B2 (en) 2005-09-01 2013-01-29 Novartis Vaccines And Diagnostics Gmbh Multiple vaccination including serogroup C Meningococcus
US20100034847A1 (en) * 2005-09-01 2010-02-11 Astrid Borkowski Multiple vaccination including Serogroup C Meningococcus
US8007807B2 (en) * 2005-09-01 2011-08-30 Novartis Vaccines And Diagnostics Gmbh Multiple vaccination including serogroup C meningococcus
US8444992B2 (en) 2005-09-01 2013-05-21 Novartis Vaccines And Diagnostics Gmbh Multiple vaccination including serogroup C meningococcus
US8784826B2 (en) 2005-09-01 2014-07-22 Novartis Ag Multiple vaccination including serogroup C meningococcus
US10406220B2 (en) 2006-05-08 2019-09-10 Wyeth Llc Pneumococcal dosing regimen
US9669084B2 (en) 2006-05-08 2017-06-06 Wyeth Llc Pneumococcal dosing regimen
US11167020B2 (en) 2006-05-08 2021-11-09 Wyeth Llc Pneumococcal dosing regimen
US8808707B1 (en) 2006-05-08 2014-08-19 Wyeth Llc Pneumococcal dosing regimen
US9603977B2 (en) 2006-06-30 2017-03-28 Institut Pasteur Use of bacterial polysaccharides for biofilm inhibition
US9603979B2 (en) 2006-06-30 2017-03-28 Institut Pasteur Use of bacterial polysaccharides for biofilm inhibition
US20090318382A1 (en) * 2006-06-30 2009-12-24 Institut Pasteur Use of bacterial polysaccharides for biofilm inhibition
US8956625B2 (en) * 2006-09-07 2015-02-17 Glaxosmithkline Biologicals, S.A. Inactivated polio vaccines
US8945582B2 (en) 2006-09-07 2015-02-03 Glaxosmithkline Biologicals S.A. Vaccine
US20100040647A1 (en) * 2006-09-07 2010-02-18 Glaxosmithkline Biologicals S.A. Vaccine
US20100034850A1 (en) * 2006-09-07 2010-02-11 Herve De Hemptinne Vaccine
US20110182942A1 (en) * 2008-05-30 2011-07-28 Wendell David Zollinger Meningococcal multivalent native outer membrane vesicle vaccine, methods of making and use thereof
US9387239B2 (en) 2008-05-30 2016-07-12 U.S. Army Medical Research And Materiel Command Meningococcal multivalent native outer membrane vesicle vaccine, methods of making and use thereof
US20110195086A1 (en) * 2010-02-09 2011-08-11 Caulfield Michael J 15-valent pneumococcal polysaccharide-protein conjugate vaccine composition
US8192746B2 (en) * 2010-02-09 2012-06-05 Merck Sharp & Dohme Corp. 15-valent pneumococcal polysaccharide-protein conjugate vaccine composition
US11160855B2 (en) * 2014-01-21 2021-11-02 Pfizer Inc. Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof
US11872274B2 (en) 2014-01-21 2024-01-16 Pfizer Inc. Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof
US20180099039A1 (en) * 2014-01-21 2018-04-12 Pfizer Inc. Immunogenic Compositions Comprising Conjugated Capsular Saccharide Antigens and Uses Thereof
US11116828B2 (en) 2017-12-06 2021-09-14 Merck Sharp & Dohme Corp. Compositions comprising Streptococcus pneumoniae polysaccharide-protein conjugates and methods of use thereof
US11850278B2 (en) 2017-12-06 2023-12-26 Merck Sharp & Dohme Llc Compositions comprising Streptococcus pneumoniae polysaccharide-protein conjugates and methods of use thereof
US12097250B2 (en) 2017-12-06 2024-09-24 Merck Sharp & Dohme Llc Compositions comprising Streptococcus pneumoniae polysaccharide-protein conjugates and methods of use thereof
US11642406B2 (en) 2018-12-19 2023-05-09 Merck Sharp & Dohme Llc Compositions comprising Streptococcus pneumoniae polysaccharide-protein conjugates and methods of use thereof
US12016914B2 (en) 2018-12-19 2024-06-25 Merck Sharp & Dohme Llc Compositions comprising Streptococcus pneumoniae polysaccharide-protein conjugates and methods of use thereof
CN111821432A (zh) * 2020-08-05 2020-10-27 北京智飞绿竹生物制药有限公司 一种多价肺炎球菌结合疫苗

Also Published As

Publication number Publication date
SI1946769T1 (sl) 2012-07-31
AU8189501A (en) 2002-01-08
KR20070091698A (ko) 2007-09-11
EP1296715A2 (fr) 2003-04-02
EA011480B1 (ru) 2009-04-28
AU2001281895B2 (en) 2005-04-28
HU1000594D0 (en) 2010-12-28
EA006313B1 (ru) 2005-10-27
SI1296715T1 (sl) 2012-03-30
CN1449293B (zh) 2012-08-22
CA2412497C (fr) 2012-10-02
CA2783274C (fr) 2018-08-07
JP2010163453A (ja) 2010-07-29
NZ523319A (en) 2006-01-27
WO2002000249A3 (fr) 2002-06-13
NO332495B1 (no) 2012-10-01
KR100898845B1 (ko) 2009-05-21
EA200501070A1 (ru) 2006-02-24
KR100837917B1 (ko) 2008-06-13
DZ3399A1 (fr) 2002-01-03
WO2002000249A2 (fr) 2002-01-03
JP2004501873A (ja) 2004-01-22
NO20026175D0 (no) 2002-12-20
EP1946769A3 (fr) 2008-07-30
DK1296715T3 (da) 2012-02-13
SK288007B6 (sk) 2012-10-02
BRPI0112057B1 (pt) 2016-10-04
BR122012003821B8 (pt) 2021-05-25
SI1296715T2 (sl) 2016-03-31
BG66238B1 (bg) 2012-08-31
SK18432002A3 (sk) 2003-08-05
BG110518A (bg) 2010-04-30
AP2002002700A0 (en) 2002-12-31
OA12302A (en) 2003-10-24
PE20020126A1 (es) 2002-04-27
MY133981A (en) 2007-11-30
BRPI0112057B8 (pt) 2021-05-25
JP5346308B2 (ja) 2013-11-20
CA2783274A1 (fr) 2002-01-03
CZ20024224A3 (cs) 2003-05-14
EP1296715B1 (fr) 2011-11-23
UA85853C2 (uk) 2009-03-10
EP2277541A1 (fr) 2011-01-26
MXPA03000198A (es) 2004-09-13
HK1055244A1 (en) 2004-01-02
DK1296715T4 (en) 2016-03-07
PL393584A1 (pl) 2011-05-23
KR20080052700A (ko) 2008-06-11
AU2001281895C1 (en) 2005-10-27
EP1946769A2 (fr) 2008-07-23
NO20026175L (no) 2003-02-26
HU227893B1 (en) 2012-05-29
HU227613B1 (en) 2011-09-28
BG66249B1 (en) 2012-09-28
US20120207780A1 (en) 2012-08-16
DK1946769T3 (da) 2012-07-16
UA76952C2 (uk) 2006-10-16
CY1112915T1 (el) 2016-04-13
BR0112057A (pt) 2003-06-17
CN101708333B (zh) 2014-03-26
EA200201240A1 (ru) 2003-06-26
PT1296715E (pt) 2012-01-19
IL153506A (en) 2009-06-15
IL153506A0 (en) 2003-07-06
ES2375704T3 (es) 2012-03-05
HUP0301413A1 (hu) 2003-08-28
EP2279748A1 (fr) 2011-02-02
CY1112280T1 (el) 2015-12-09
EP1296715B2 (fr) 2015-12-23
MA25824A1 (fr) 2003-07-01
EG24742A (en) 2010-07-14
CN101708333A (zh) 2010-05-19
PL210015B1 (pl) 2011-11-30
KR20030024714A (ko) 2003-03-26
CN1449293A (zh) 2003-10-15
ATE534402T1 (de) 2011-12-15
HU1000593D0 (en) 2010-12-28
BR122012003821B1 (pt) 2020-09-01
ES2385100T3 (es) 2012-07-18
EP1946769B1 (fr) 2012-05-30
CA2412497A1 (fr) 2002-01-03
US9233151B2 (en) 2016-01-12
ES2375704T5 (es) 2016-03-03
PL360265A1 (en) 2004-09-06
UY26801A1 (es) 2002-01-31
JP4870895B2 (ja) 2012-02-08
BG107422A (bg) 2003-09-30
AP1695A (en) 2006-12-17
PT1946769E (pt) 2012-06-27
HU228384B1 (en) 2013-03-28
HUP0301413A3 (en) 2010-01-28

Similar Documents

Publication Publication Date Title
US9233151B2 (en) Vaccine composition
EP1946771B1 (fr) Composition vaccinale
AU2001281895A1 (en) Vaccine Composition
AU2010235979A1 (en) Vaccine composition
ZA200300755B (en) Multivalent vaccine composition.
AU2005203302A1 (en) Vaccine composition
AU2002310903A1 (en) Vaccine composition

Legal Events

Date Code Title Description
AS Assignment

Owner name: GLAXOSMITHKLINE BIOLOGICALS S.A. (FORMERLY SMITHKL

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BOUTRIAU, DOMINIQUE;CAPIAU, CARINE;DESMONS, PIERRE MICHEL;AND OTHERS;REEL/FRAME:013518/0345;SIGNING DATES FROM 20030217 TO 20030227

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION