Preclinical evaluation of a novel group B meningococcal conjugate vaccine that elicits bactericidal activity in both mice and nonhuman primates.
Group B meningococcal (GBM) conjugate vaccines were prepared using chemically modified N-propionylated polysialic acid, from Escherichia coli K1 polysaccharide capsule, coupled by reductive amination to tetanus toxoid and purified recombinant GBM porin (rPorB). All conjugates elicited high antibody levels in mice with good booster responses. However, only rPorB conjugates elicited bactericidal activity specific against a broad spectrum of five different GBM serotypes. Bactericial activity was completely inhibited by free N-propionylated polysaccharide. In baboons and rhesus monkeys, rPorB conjugates elicited high antibody titers, with IgG booster responses 9- to 15-fold higher than primary responses. Bactericial activity increased 19- to 39-fold over preimmune values, using rabbit complement; increased bactericial activity was also confirmed with human and monkey complement. IgG cross-reactivity for unmodified N-acetyl polysaccharide was <5% for 79% of mice and <10% for 80% of primates. These studies strongly suggest that the N-propionylated polysialic acid-rPorB conjugate is an excellent vaccine candidate for human use.
Fusco
P C
PC
North American Vaccine, Inc., Beltsville, Maryland 20705, USA.
Michon
F
F
Tai
J Y
JY
Blake
M S
MS
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008253:Macaca mulatta; D008585:Meningitis, Meningococcal / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D010215:Papio; D011134:Polysaccharides / Q000494:pharmacology; D018272:Porins; D011994:Recombinant Proteins / Q000276:immunology; D012794:Sialic Acids / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology*
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D007074:Immunoglobulin G; D011134:Polysaccharides; D018272:Porins; D011994:Recombinant Proteins; D012794:Sialic Acids; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; C057699:porin protein, Neisseria; D003165:Complement System Proteins