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

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.