Pc. Fusco et al., PRECLINICAL EVALUATION OF A NOVEL GROUP-B MENINGOCOCCAL CONJUGATE VACCINE THAT ELICITS BACTERICIDAL ACTIVITY IN BOTH MICE AND NONHUMAN-PRIMATES, The Journal of infectious diseases, 175(2), 1997, pp. 364-372
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.