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WO2007113598A2 - Compositions vaccinales - Google Patents

Compositions vaccinales Download PDF

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Publication number
WO2007113598A2
WO2007113598A2 PCT/GB2007/050181 GB2007050181W WO2007113598A2 WO 2007113598 A2 WO2007113598 A2 WO 2007113598A2 GB 2007050181 W GB2007050181 W GB 2007050181W WO 2007113598 A2 WO2007113598 A2 WO 2007113598A2
Authority
WO
WIPO (PCT)
Prior art keywords
6bpp
peptide
seq
binding fragment
conjugate
Prior art date
Application number
PCT/GB2007/050181
Other languages
English (en)
Other versions
WO2007113598A3 (fr
Inventor
Peter Andrew
Claire Mary Smith
Carla Lopasso
Helen Baxendale
David Goldblatt
Franco Felici
Original Assignee
University Of Leicester
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 University Of Leicester filed Critical University Of Leicester
Publication of WO2007113598A2 publication Critical patent/WO2007113598A2/fr
Publication of WO2007113598A3 publication Critical patent/WO2007113598A3/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1267—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
    • C07K16/1275—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Streptococcus (G)
    • 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
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/195—Assays involving biological materials from specific organisms or of a specific nature from bacteria
    • G01N2333/315—Assays involving biological materials from specific organisms or of a specific nature from bacteria from Streptococcus (G), e.g. Enterococci

Definitions

  • This invention relates to peptide mimetics of carbohydrate antigens and conjugates thereof, compositions comprising such mimetic peptides or conjugates, and their use to provide protection against pneumococcal infection, in particular infection caused by Streptococcus pneumoniae (S. pneumoniae) serotype 6B.
  • the invention further relates to mimetic peptides, or conjugates thereof, for use as medicaments, and in the manufacture of medicaments for the treatment of pneumococcal infection.
  • the invention also relates to methods for prophylactic or therapeutic treatment of pneumococcal infection, involving administration of a mimetic peptide or a conjugate thereof, or of a composition comprising a mimetic peptide or conjugate thereof.
  • This invention further relates to vaccine compositions comprising antibody, in particular monoclonal antibody (mAb), raised against serotype 6B S. pneumoniae or comprising a S. pneumoniae serotype 6B pneumococcal polysaccharide (6BPP) binding fragment of the mAb, and their use to prevent or treat pneumococcal infection, in particular infection caused by S. pneumoniae serotype 6B.
  • mAb monoclonal antibody
  • 6BPP pneumococcal polysaccharide
  • the invention further relates to such antibody or a 6BPP binding fragment thereof for use as a medicament and in the manufacture of a medicament for prophylactic or therapeutic treatment of pneumococcal infection.
  • the invention relates to methods for prophylactic or therapeutic treatment of pneumococcal infection involving administration of a monoclonal antibody, raised against serotype 6B S. pneumoniae, or a 6BPP binding fragment thereof of the mAb, or of a composition comprising monoclonal antibody raised against serotype 6B S. pneumoniae or comprising a 6BPP binding fragment of the mAb.
  • Streptococcus pneumoniae is an encapsulated gram-positive bacterium, it is a leading cause of pneumonia, meningitis and bacteraemia in young children, the elderly and the immunocompromised, with the result that it is a major cause of morbidity and mortality in the developed world (Mims et a/, 1999).
  • the main target of the immune system during infection is the polysaccharide capsule that surrounds the organism; however, because of its carbohydrate constitution, a T cell-independent (Tl) immune response is stimulated.
  • Tl antigens stimulate B cells to differentiate into short-lived antibody producing plasma cells; this response will clear infection, but does not confer lasting immunity.
  • Tl Tl-independent
  • protein epitopes are T-dependant (TD) antigens, which means that T-celis are involved in recognition of the protein epitopes and that the T-cells activate memory B cell proliferation, to achieve an effective, long-lasting immune response.
  • TD T-dependant
  • Pneumovax® 23 vaccine (Merck & Co., Inc.) is a polyvalent vaccine that consists of highly purified capsular polysaccharide from the 23 most prevalent or invasive pneumococcal types of S. pneumoniae found in the US and Europe (1 , 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V 1 10A, 11A 1 12F 1 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F).
  • the Pneumovax® 23 vaccine offers only a protective efficacy of 60-70% and can be even less effective in the most susceptible group, young children. The limited efficacy of this vaccine is because it is a polysaccharide vaccine, i.e. it contains carbohydrate antigen and thus elicits oniy a Tl response.
  • the vaccine includes serotypes 4, 6B, 9V, 14, 18C, 19F, 23F conjugated to Diptheria CRM 197 protein. This vaccine is reported to show promising results and to confer protection against 71-86% of childhood infectious pneumococcal diseases in Europe.
  • PrevnarTM vaccine is expensive because of the complicated and expensive techniques required for production of the subcomponents. Also, three doses are needed to obtain complete protection. There is a reduction in vaccine coverage, as less serotypes (subcomponents) can be included at an affordable end cost.
  • the peptide mimetopes were shown to structurally mimic carbohydrate antigens; to induce carbohydrate-reactive B-cell and T-cell responses after immunisation; and, after priming, enhance responses upon boosting with carbohydrate (Kieber-Emmons 1998).
  • Peptide mimetopes of carbohydrate antigens can be identified by analysis of the interaction between anti-carbohydrate antibodies and monoclonal anti-idiotypic antibodies.
  • peptide mimetopes can be obtained by screening phage display peptide libraries using monoclonal anti-carbohydrate antibodies. Not ail peptide mimetopes are immunogenic, and not all immunogenic peptide mimetopes will elicit a protective immune response. The only method currently available to determine if an epitope elicits a protective immune response is to immunise with the epitope and then challenge by infection.
  • the present invention provides a 6B pneumococcal polysaccharide (6BPP) peptide mimetope.
  • 6BPP 6B pneumococcal polysaccharide
  • the peptide mimetope can be conjugated to a carrier protein.
  • Peptide mimetopes, or conjugates thereof, in accordance with the invention are capable of stimulating a protective immune response against pneumococcal infection.
  • the 6BPP peptide mimetope comprises an amino acid sequence selected from SEQ ID NO: 1 , SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 and SEQ ID NO: 7.
  • the 6BPP peptide mimetope may be provided as a conjugate comprising a carrier protein and a peptide having an amino acid sequence selected from SEQ ID NO: 1 , SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 and SEQ ID NO: 7.
  • Suitable carrier proteins include keyhole limpet haemocyanin (KLH), bovine serum albumin (BSA), Glutathione-S-Transferase (GST), Tetanus toxoid, Diptheria toxin or Diptheria CRM protein.
  • KLH keyhole limpet haemocyanin
  • BSA bovine serum albumin
  • GST Glutathione-S-Transferase
  • Tetanus toxoid Tetanus toxoid
  • Diptheria toxin Diptheria CRM protein.
  • Peptide mimetopes and conjugates are preferably produced by chemical synthesis, although recombinant methods can also be used.
  • the invention further provides a composition comprising a 6BPP peptide mimetope or a conjugate thereof according to the invention and an excipient.
  • the composition is a pharmaceutical composition suitable for administration to a human or animal subject and the excipient is a pharmaceutically acceptable excipient.
  • the invention provides a 6BPP peptide mimetope or a conjugate thereof, or of a composition according to the invention comprising a 6BPP peptide mimetope or a conjugate thereof, for use as a medicament.
  • a 6BPP peptide mimetope or conjugate thereof or a composition according to the invention comprising a 6BPP peptide mimetope or a conjugate thereof, in the manufacture of a medicament.
  • a 6BPP peptide mimetope, or conjugate thereof, or a composition according to the invention comprising a 6BPP peptide mimetope or a conjugate thereof in the manufacture of a medicament for the prevention or treatment of pneumococcal infection, in particular S. pneumoniae 6B infection.
  • the invention provides a method of treating a human or animal subject, comprising administering to the subject an amount of a 6BPP mimetic peptide or a conjugate thereof according to the invention, or a composition according to the invention comprising a 6BPP peptide mimetope or a conjugate thereof, effective to prevent or treat pneumococcal infection, in particular S. pneumoniae 6B infection.
  • the invention provides a pharmaceutical composition, suitably a medicament, comprising an antibody, preferably a monoclonal antibody, specific for a 6BPP peptide, e.g. the monoclonal antibody Db3G9, or a 6BPP ⁇ binding fragment thereof, and a pharmaceutically acceptable excipient.
  • a pharmaceutical composition suitably a medicament, comprising an antibody, preferably a monoclonal antibody, specific for a 6BPP peptide, e.g. the monoclonal antibody Db3G9, or a 6BPP ⁇ binding fragment thereof, and a pharmaceutically acceptable excipient.
  • Suitable 6BPP binding fragments of the antibody include Fab fragments, F(ab') 2 fragments and fragments produced by a Fab expression library.
  • the 6BPP-binding fragments of the invention are capable of binding epitopes found on serotype 6B S. pneumoniae.
  • antibody as used herein includes, but is not limited to: polyclonal, monoclonal, bispecific, humanised or chimeric antibodies, single chain antibodies, anti-idiotypic (anti-Id) antibodies, and epitope-binding fragments of any of the above.
  • antibody as used herein also refers to immunoglobulin molecules.
  • the immunoglobulin molecules of the invention can be of any class (e. g., IgG, IgE, IgM, IgD and IgA) or subclass of immunoglobulin molecule.
  • an antibody preferably a monoclonal antibody, specific for a 6BPP peptide, e.g. the monoclonal antibody Db3G9, or a 6BPP-binding fragment thereof, or a composition comprising an antibody, preferably a monoclonal antibody, specific for a 6BPP peptide, e.g. the monoclonal antibody Db3G9, or a 6BPP-binding fragment thereof for use as a medicament.
  • a monoclonal antibody specific for a 6BPP peptide, e.g. the monoclonal antibody Db3G9, or a 6BPP-binding fragment thereof
  • a composition comprising an antibody, preferably a monoclonal antibody, specific for a 6BPP peptide, e.g. the monoclonal antibody Db3G9, or a 6BPP-binding fragment thereof for use as a medicament.
  • an antibody preferably a monoclonal antibody, specific for a 6BPP peptide, e.g. Db3G9, or a 6BPP-binding fragment thereof in the manufacture of a medicament.
  • an antibody preferably a monoclonal antibody, specific for a 6BPP peptide, e.g. the monoclonal antibody Db3G9, or a 6BPP-binding fragment thereof, in the manufacture of a medicament for the prevention or treatment of pneumococcal infection, in particular S. pneumoniae 6 B infection.
  • the invention provides a method of treating a human or animal subject, comprising administering to the subject an amount of an antibody, preferably a monoclonal antibody, specific for a 6BPP peptide, e.g. the monoclonal antibody Db3G9, or a 6BPP-binding fragment thereof, or a pharmaceutical composition comprising said antibody or binding fragment thereof, effective to prevent or treat pneumococcal infection, in particular S. pneumoniae 6B infection.
  • an antibody preferably a monoclonal antibody, specific for a 6BPP peptide, e.g. the monoclonal antibody Db3G9, or a 6BPP-binding fragment thereof, or a pharmaceutical composition comprising said antibody or binding fragment thereof, effective to prevent or treat pneumococcal infection, in particular S. pneumoniae 6B infection.
  • the invention further provides a method of conferring protective immunity against a pneumococcal infection comprising administering to a human or animal subject an effective amount of an antibody, preferably a monoclonal antibody, specific for a 6BPP peptide, e.g. DB3G9, or a 6BPP-binding fragment thereof, or a composition comprising an antibody, preferably a monoclonal antibody, specific for a 6BPP peptide, e.g. DB3G9, or a 6BPP-binding fragment thereof.
  • an antibody preferably a monoclonal antibody, specific for a 6BPP peptide, e.g. DB3G9, or a 6BPP-binding fragment thereof.
  • compositions according to the invention may be provided in solution or dried (e.g. lyophilised) form.
  • the composition may be provided as a solution in a form suitable for administration to a subject, e.g. as a solution in excipients such as physiological saline or aqueous buffer.
  • compositions according to the invention may be in a form suitable for reconstitution in an appropriate liquid for administration.
  • suitable liquid media for reconstitution include sterile distilled water or physiological saline, which may be buffered e.g. with phosphate buffer.
  • a medicament or pharmaceutical composition according to the present invention is preferably provided in injectable form, most preferably for intradermal, subcutaneous or intramuscular injection.
  • compositions may be provided dried or in solution, separately or together, e.g. in a vial or vials or in a pre-filled syringe or syringes.
  • the composition may be provided in a form suitable for orai administration, e.g. tablet, capsule, sachet, cachet, solution or suspension.
  • the composition can be administered by a route selected from parenteral, intradermal, subcutaneous, intravenous, inhalation, intranasal, intramuscular, intraperitoneal, transdermal, sublingual, buccal, rectal or mucosal routes.
  • the dosage administered will be dependent upon the age, health, and weight of the recipient, frequency of treatment and the nature of the effect desired.
  • a composition according to the invention may be administered as a single immunisation to provide protective immunity, or may be administered as a series of immunisations over a suitable time period, e.g. two or three immunisations at monthly intervals.
  • a medicament according to the invention will comprise a therapeutically effective amount of the active ingredient.
  • the active ingredient is 6BPP mimetope, or a 6BPP peptide mimetope-carrier protein conjugate, this is present in an amount sufficient to stimulate a protective immune response against pneumococcal infection, in particular S. pneumoniae 6B infection.
  • the active ingredient is an antibody, preferably a monoclonal antibody, specific for a 6BPP peptide, e.g. DB3G9, or a 6BPP-binding fragment thereof, it is present in an amount sufficient to confer passive immunity and thereby provide a protective immune response.
  • an antibody preferably a monoclonal antibody, specific for a 6BPP peptide, e.g. DB3G9, or a 6BPP-binding fragment thereof.
  • a composition according to the invention may contain suitable pharmaceutically acceptable excipients such as carriers or diluents, that facilitate processing of the active compounds into pharmaceutical/medicament preparations.
  • suitable formulations for parenteral administration preferably intramuscular injection include aqueous solutions of the active compounds, for example in saline.
  • suspensions of the active components as appropriate oily injection suspensions may be administered.
  • Suitable lipophilic solvents or vehicles include fatty oils, for example, sesame oil, or synthetic fatty acid esters, for example, ethyl oleate or triglycerides.
  • Aqueous injection suspensions may contain substances which increase the viscosity of suspension which include, for example, sodium carboxymethyl cellulose, sorbitol, and/or dextran.
  • the suspension may also contain stabilizers or preservatives. As a preservative phenol may be included, e.g. at about 0.25% (w/v). Liposomes can also be used to encapsulate the agent for
  • a composition for systemic administration according to the invention may be formulated for enteral, parenteral or topical administration.
  • suitable compositions for oral administration include hard or soft gelatin capsules, pills, tablets, including coated tablets, elixirs, suspensions, syrups or inhalations and controlled release forms thereof.
  • Suitable composition for administration by inhalation include metered dose inhalers and dry powder devices. For nasai absorption aqueous and non-aqueous suspensions or dry powders may be used.
  • a medicament/pharmaceutical composition according to the invention may comprise an adjuvant (such as aluminium hydroxide) or other substance to further stimulate/potentiate the immune response to the immunogen(s) of the vaccine.
  • an adjuvant such as aluminium hydroxide
  • other substance to further stimulate/potentiate the immune response to the immunogen(s) of the vaccine.
  • the 6BPP mimetic peptides of accordance with the invention are also useful for research purposes, in particular the in methods for the selection, enrichment and study of antigen specific B cells and in methods to assess antibody responses to pneumococcal antigens and cross reactive antigens.
  • the mimetic peptides of the invention can be used in research in methods to compare the B cell repertoire induced by mimotope and native PS/PS conjugate vaccines and also in methods for evaluation of T cell response to pneumococcal polysaccharide mimics.
  • Figure 1 Assessment of parent mAb (Db3G9) binding to mimetic peptides/BSA conjugates, assessed by ELISA.
  • FIG. 1 Survival following pneumococcal challenge.
  • Figure 3 Correlation of peptide induced immune serum activity against peptide and pneumococcus polysaccharide (Pnc PS) by ELISA.
  • Figure 4 Correlation of anti-peptide antibody concentration post-immunisation and survival.
  • Figure 5 Correlation of pneumococcus polysaccharide ⁇ Pnc PS) antibody concentration post-peptide immunisation and survival.
  • the mAb Db3G9 ( ⁇ Baxendale et a/., 2000) was used to screen a phage display peptide library (Felici et al (1991)) located in the laboratory of Franco Felici, University of Messina, Messina, Italy.
  • the library provided 7 peptides, termed MP 2, 10, 13, 14, 15, 17 and 18.
  • the peptide MP13 (SEQ ID NO: 5 ), was shown to compete binding of the monoclonal antibody equally between phage- displayed peptide and native polysaccharide antigen in ELISA.
  • the MP 13 peptide was synthesised (Thermohybaid) with KLH (Keyhole Limpet Haemacyanin) or BSA (Bovine Serum Albumin) N-conjugated.
  • KLH Keyhole Limpet Haemacyanin
  • BSA Bovine Serum Albumin
  • a dose per mouse of 50 ⁇ g/100 ⁇ l of KLH conjugated peptide in phosphate buffered saline (PBS) was used to immunise 2 groups of 15 MF1 mice, 15 control MF1 mice received only KLH (Calbiochem®, UK) at 50 ⁇ g/100 ⁇ l of PBS.
  • Mice were then challenged on day 5 with type 6B pneumococcus at a dose of 1x10 6 cfu/100 ⁇ l intraperitoneal ⁇ (i.p.).
  • mice After immunisation with KLH-peptide MP13 conjugate, mice were shown to have a survival of almost 60%, compared with about 20% in the non-immunised control group ( Figure 2). This was a significant difference and gave a P value of less than 0.05 when survival curve analysis was performed (using the GraphPad Prism 4 statistical program).
  • a monoclonal antibody (mAb) raised against serotype 6B S. pneumoniae was provided as an ascites fluid . This was diluted 1 :2 in PBS and 100 ⁇ l used to passively immunise 10 female MF1 mice (Harlan, UK) intraperitoneal ⁇ (i.p.) at Time -1 , an hour prior to challenge.
  • the 10 immunised mice and 10 (non-immunised) control MF1 mice were challenged i.p. with 100 ⁇ l 2x10 7 cfu/100ul type 6B pneumococci; a dose previously shown to induce symptoms of pneumococcal disease.
  • Their health status was monitored for 240 hours and mice were culled when symptoms (including hunching, production of starry coat and lethargy) progressed to an almost moribund stage.
  • mice passively immunised with the lgG2 monoclonal antibody] were shown to have a far higher survival rate compared to the non-immunised control mice. No immunised mice were shown to develop any symptoms of disease until 24 hours after the first mortalities were recorded in the non-immunised control group.
  • Hybridomas An adult human subject (D) was immunized with heptavalent pneumococcal- mutant diphtheria toxin (CRMi 97 ) conjugate vaccine (7V-CRMi 97 ). Three stable hybridomas were generated . One of these stable hybridomas produced an lgG2 monoclonal antibody, termed Db3G9.
  • a healthy adult volunteer was recruited and given a single dose of 7V-CRM 197 containing 2 ⁇ g each of 4, 9V, 14, 18C, 19F, 23F and 4 ⁇ g of 6B conjugated to a mutant diphtheria toxin (Prevnar TM Wyeth Lederle Vaccines and Paediatrics, NY). Blood was taken immediately prior to vaccination and on days 7 and 28 post vaccination. Lymphocytes were isolated by Ficoll density centrifugation from day 7 venesections while sera obtained at each time point were separated and stored at - 80 °C.
  • Day 7 lymphocytes were fused using PEG (PEG 4000, Gibco-BRL, NY) to the non-secreting mouse myeloma line OURI, Thompson et al. (1991) and plated onto a mouse fibroblast feeder layer in 96-well tissue culture plates (Nunc, Life Technologies, Paisley, GB). The cells were incubated at 37 °C in 5% CO 2 for 2 to 3 weeks and then screened for pneumococcus-specific antibody production. Positive wells were subcloned twice by limiting dilution and the cell lines then expanded in standard tissue culture flasks.
  • PEG PEG 4000, Gibco-BRL, NY
  • Serotype-specific pneumococcal antibody titers were determined by ELISA as previously described (Kayhty et al. (1995)) with some adaptions to make the ELISA suitable for culture supernatant screening.
  • Nunc 96-well maxisorp plates (Life Technologies, Paisley, GB) were coated for 5 h at 37 0 C with a heptavalent antigen mix prediluted in PBS comprising pneumococcal capsular polysaccharide serotypes 4, 6B, 19F at 20 ⁇ g/ml, 9V, 14 and 23F at 10 ⁇ g/ml and 18C at 2 ⁇ g/ml (obtained from American Type Tissue Collection, Rockville, MD).
  • PBS-T PBS/0.05% Tween
  • Cell supernatants were diluted by 50% in PBS-T with 1 % BSA (BSA PBS-T), and then added directly to the coated plates and incubated for 2 h at room temperature. Plates were then washed five times and the second antibody, horseradish peroxidase (HRP)-conjugated goat anti-human polyvalent IgG (Sigma, Dorset, GB), was added at a 1/2000 dilution in BSA PBS-T. Following a further 2 hour incubation at room temperature, well were washed again five times with PBS-T and substrate added.
  • HRP horseradish peroxidase
  • Serospecificity of the mAb was confirmed by inhibition assay. Non-specific binding to CWPS was excluded by preincubating supernatant diluted 50% in PBS-T-B with CWPS (Statens Seruminstitut, Copenhagen, Denmark) at a final concentration of 50 ⁇ g/ml. Cross-reactivity with other serotypes was evaluated by pre-incubating antibody at a dilution pre-determined to give an OD of 1.0 on ELlSA for 30 min with 50 ⁇ g/ml (final concentration) of homologous or heterologous capsular polysaccharide and then performing the standard ELISA.

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Abstract

L'invention concerne un mimotope peptidique de polysaccharide pneumococcique de sérotype 6B (6BPP) de Streptococcus pneumoniae, éventuellement conjugué à une protéine support, capable de stimuler une réponse immunitaire protectrice contre une infection pneumococcique. L'invention concerne également un anticorps monoclonal (AcM) dirigé contre un polysaccharide pneumococcique 6B et des fragments de liaison à 6BPP correspondants, pouvant conférer une immunité passive contre une infection pneumococcique. Par ailleurs, l'invention concerne des compositions comprenant ce mimotope peptidique, ce conjugué, cet AcM ou un fragment de liaison correspondant. Les peptides mimétiques, leurs conjugués, l'AcM et les fragments de liaison à 6BPP de l'invention sont utilisés comme médicaments et dans la fabrication de médicaments destinés à traiter une infection pneumococcique. L'invention se rapporte en outre à des méthodes de traitement prophylactique ou thérapeutique d'une infection pneumococcique.
PCT/GB2007/050181 2006-04-05 2007-04-05 Compositions vaccinales WO2007113598A2 (fr)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9714283B2 (en) 2014-10-28 2017-07-25 Adma Biologics, Inc. Compositions and methods for the treatment of immunodeficiency
US10259865B2 (en) 2017-03-15 2019-04-16 Adma Biologics, Inc. Anti-pneumococcal hyperimmune globulin for the treatment and prevention of pneumococcal infection

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6528061B1 (en) * 1997-09-04 2003-03-04 Pasteur Institut Immunogenic polypeptides that mimic a surface polysaccharide antigen of a pathogenic microorganism, method for obtaining the same, and their use in vaccine compositions
WO2002079254A1 (fr) * 2001-03-29 2002-10-10 Janoff Edward N Anticorps monoclonaux humains contre des polysaccharides capsulaires de streptococcus pneumoniae

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9714283B2 (en) 2014-10-28 2017-07-25 Adma Biologics, Inc. Compositions and methods for the treatment of immunodeficiency
US9815886B2 (en) 2014-10-28 2017-11-14 Adma Biologics, Inc. Compositions and methods for the treatment of immunodeficiency
US9969793B2 (en) 2014-10-28 2018-05-15 Adma Biologics, Inc. Compositions and methods for the treatment of immunodeficiency
US10683343B2 (en) 2014-10-28 2020-06-16 Adma Biologics, Inc. Compositions and methods for the treatment of immunodeficiency
US11339206B2 (en) 2014-10-28 2022-05-24 Adma Biomanufacturing, Llc Compositions and methods for the treatment of immunodeficiency
US11780906B2 (en) 2014-10-28 2023-10-10 Adma Biomanufacturing, Llc Compositions and methods for the treatment of immunodeficiency
US10259865B2 (en) 2017-03-15 2019-04-16 Adma Biologics, Inc. Anti-pneumococcal hyperimmune globulin for the treatment and prevention of pneumococcal infection
US11084870B2 (en) 2017-03-15 2021-08-10 Adma Biologics, Inc. Anti-pneumococcal hyperimmune globulin for the treatment and prevention of pneumococcal infection
US11897943B2 (en) 2017-03-15 2024-02-13 Adma Biomanufacturing, Llc Anti-pneumococcal hyperimmune globulin for the treatment and prevention of pneumococcal infection

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WO2007113598A3 (fr) 2007-12-06

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