title: Preparation and characterization of an immunogenic meningococcal group A conjugate vaccine for use in Africa.
abstract: Periodic epidemics of group A meningococcal (Mn A) meningitis continue to occur in sub-Saharan Africa. For its prevention, a Mn A polysaccharide (PS)-tetanus toxoid (TT) conjugate vaccine was developed using reductive amination of polysaccharide aldehydes and toxoid hydrazides. In mouse immunization studies, a schedule of three bi-weekly s.c. immunizations of 0.1 or 1mug of the conjugate (PS content) without an adjuvant induced serum antibody levels of >10,000units/mL measured by enzyme-linked immunosorbent assay (ELISA) as compared to approximately 100units/mL in PS control mice. The elicited antibodies were active in bactericidal assays using either baby rabbit or human complement (titers >1500 compared to approximately 200 for the PS control group). The synthesis process is reproducible and scalable, and has been successfully used for manufacturing a Mn A PS-TT conjugate vaccine based on a paradigm of shared manufacturing with transfer of new technology [Jodar L, LaForce FM, Ceccarini C, Aguado T, Granoff DM. Meningococcal conjugate vaccine for Africa: a model for development of new vaccine for the poorest countries. Lancet 2003, 361:1092-4]. A phase 1 clinical trial of the manufactured Men A-TT conjugate vaccine has been successfully carried out in adults in India, and a phase 2 clinical trial in young children is currently underway in Africa.
authors.affiliation: Center for Biologics Evaluation and Research, Bethesda, MD 20892, USA. robert.lee@fda.hhs.gov
authors.forename: Che-Hung
authors.initials: CH
authors.lastname: Lee
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Kuo
authors.forename: Suresh
authors.initials: S
authors.lastname: Beri
authors.forename: Subash
authors.initials: S
authors.lastname: Kapre
authors.forename: Jayant S
authors.initials: JS
authors.lastname: Joshi
authors.forename: Nancy
authors.initials: N
authors.lastname: Bouveret
authors.forename: F Marc
authors.initials: FM
authors.lastname: LaForce
authors.forename: Carl E
authors.initials: CE
authors.lastname: Frasch
mesh_terms: D000328:Adult; D000349:Africa; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007117:Immunization, Secondary; D007194:India; D007279:Injections, Subcutaneous; D008585:Meningitis, Meningococcal / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D050296:Microbial Viability; D038381:Neisseria meningitidis, Serogroup A / Q000276:immunology*; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage
chemical_list: D000907:Antibodies, Bacterial; D022401:Meningococcal Vaccines; D013745:Tetanus Toxoid; D017778:Vaccines, Combined; D018074:Vaccines, Conjugate