PRECLINICAL EVALUATION OF A NOVEL GROUP-B MENINGOCOCCAL CONJUGATE VACCINE THAT ELICITS BACTERICIDAL ACTIVITY IN BOTH MICE AND NONHUMAN-PRIMATES

Group B meningococcal (GEM) conjugate vaccines were prepared using che mically modified N-propionylated polysialic acid, from Escherichia col i K1 polysaccharide capsule, coupled by reductive amination to tetanus toroid and purified recombinant GEM porin (rPorB), All conjugates eli cited high antibody levels in mice with good booster responses, Howeve r, only rPorB conjugates elicited bactericidal activity specific again st a broad spectrum of five different GEM serotypes, Bactericial activ ity was completely inhibited by free N-propionylated polysaccharide, i n baboons and rhesus monkeys, rPorB conjugates elicited high antibody titers, with IgG booster responses 9- to 15-fold higher than primary r esponses. Bactericial activity increased 19- to 39-fold over preimmune values, using rabbit complement; increased bactericial activity was a lso confirmed with human and monkey complement. IgG cross-reactivity f or unmodified N-acetyl polysaccharide was <5% for 79% of mice and <10% for 80% of primates, These studies strongly suggest that the N-propio nylated polysialic acid-rPorB conjugate is an excellent vaccine candid ate for human use.