Preparation and characterization of an immunogenic meningococcal group A conjugate vaccine for use in Africa

Vaccine. 2009 Jan 29;27(5):726-32. doi: 10.1016/j.vaccine.2008.11.065. Epub 2008 Dec 6.

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.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Africa
  • Animals
  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunization, Secondary
  • India
  • Injections, Subcutaneous
  • Meningitis, Meningococcal / prevention & control*
  • Meningococcal Vaccines / administration & dosage
  • Meningococcal Vaccines / immunology*
  • Mice
  • Microbial Viability
  • Neisseria meningitidis, Serogroup A / immunology*
  • Tetanus Toxoid / administration & dosage
  • Tetanus Toxoid / immunology
  • Vaccines, Combined / administration & dosage
  • Vaccines, Combined / immunology
  • Vaccines, Conjugate / administration & dosage

Substances

  • Antibodies, Bacterial
  • Meningococcal Vaccines
  • Tetanus Toxoid
  • Vaccines, Combined
  • Vaccines, Conjugate