Methods for producing quadrivalent meningococcal meningitis polysaccharide
and conjugate vaccines for serotypes A, C, Y and W-135 disclosed.
Neisseria meningitidis fastidious medium was designed to maximize the
yield of capsular polysaccharides and generate minimal cellular biomass
and endotoxin in a short duration of fermentation. The crude
polysaccharides are isolated, purified, and mechanically depolymerized by
sonication. These purified polysaccharides were found in human clinical
trials to be safe and immunogenic against meningococcal disease caused by
N. meningitidis A, C, Y and W-135 serogroups in sub-Saharan Africa. In
the preferred embodiment, the polysaccharides are conjugated to carrier
proteins of diphtheria or tetanus toxiod to an average molecular size of
5100 to 9900 Daltons and provide broad spectrum protection to humans of
all ages. Accelerated polysaccharide production and the efficacy of the
resulting vaccine are demonstrated.