title: Preclinical studies on a recombinant group B meningococcal porin as a carrier for a novel Haemophilus influenzae type b conjugate vaccine.
abstract: In anticipation of future combination vaccines, a recombinant class 3 porin (rPorB) of group B meningococci was evaluated as an alternative carrier protein for a Haemophilus influenzae type b (Hib) polyribosylribotol phosphate (PRP) conjugate vaccine. The use of rPorB may avoid undesirable immunologic interactions among vaccine components, including epitopic suppression from conventional carriers (e.g. tetanus toxoid [TT]), as well as provide desirable immunomodulatory effects. Rats were found to be more reliable and consistent than mice or guinea pigs for studying antibody responses to the Hib conjugates. Different Hib conjugates, Hib-TT and Hib-rPorB, consisting of PRP conjugated by reductive amination to TT or rPorB, were compared in rats. Commercially available, licensed vaccines, HbOC (HibTITER) and PRP-T (OmniHib), were used as reference controls. Maximum geometric mean ELISA IgG titers were obtained in rats after only two doses, showing booster effects for all. However, Hib-rPorB immunization consistently resulted in responses that were 1-2 orders of magnitude greater than those for the other conjugates, including the licensed control vaccines. A maximum 4600-fold rise was observed for Hib-rPorB after two doses, and, unlike the other conjugates, a 100% response rate was always achieved without adjuvant. These results warrant further investigation of Hib-rPorB in combination with DTaP.
authors.affiliation: North American Vaccine, Inc., Beltsville, MD 20705, USA. pfusco@nava.com
authors.forename: P C
authors.initials: PC
authors.lastname: Fusco
authors.forename: F
authors.initials: F
authors.lastname: Michon
authors.forename: M
authors.initials: M
authors.lastname: Laude-Sharp
authors.forename: C A
authors.initials: CA
authors.lastname: Minetti
authors.forename: C H
authors.initials: CH
authors.lastname: Huang
authors.forename: I
authors.initials: I
authors.lastname: Heron
authors.forename: M S
authors.initials: MS
authors.lastname: Blake
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood; D016667:Bacterial Capsules; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018073:Haemophilus Vaccines / Q000276:immunology* / Q000494:pharmacology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D051379:Mice; D008815:Mice, Inbred Strains; D009345:Neisseria meningitidis / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D018272:Porins; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D013745:Tetanus Toxoid / Q000494:pharmacology; D018074:Vaccines, Conjugate / Q000494:pharmacology
chemical_list: D000914:Antibodies, Viral; D001425:Bacterial Outer Membrane Proteins; D018073:Haemophilus Vaccines; C055753:Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; C044237:Haemophilus influenzae type b polysaccharide vaccine; D007074:Immunoglobulin G; D011135:Polysaccharides, Bacterial; D018272:Porins; D011994:Recombinant Proteins; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; C057699:porin protein, Neisseria