Preclinical studies on a recombinant group B meningococcal porin as a carrier for a novel Haemophilus influenzae type b conjugate vaccine

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 immunolog...

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Veröffentlicht in:Vaccine 1998-11, Vol.16 (19), p.1842-1849
Hauptverfasser: Fusco, Peter C., Michon, Francis, Laude-Sharp, Maryline, Minetti, Conceição A.S.A., Huang, Chun-Hsien, Heron, Iver, Blake, M.S.
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container_end_page 1849
container_issue 19
container_start_page 1842
container_title Vaccine
container_volume 16
creator Fusco, Peter C.
Michon, Francis
Laude-Sharp, Maryline
Minetti, Conceição A.S.A.
Huang, Chun-Hsien
Heron, Iver
Blake, M.S.
description 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.
doi_str_mv 10.1016/S0264-410X(98)00174-1
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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.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>9795390</pmid><doi>10.1016/S0264-410X(98)00174-1</doi><tpages>8</tpages></addata></record>
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subjects Animals
Antibodies, Viral - biosynthesis
Antibodies, Viral - blood
Bacterial Capsules
Bacterial Outer Membrane Proteins - immunology
Bacteriology
Biological and medical sciences
conjugate
Enzyme-Linked Immunosorbent Assay
Female
Fundamental and applied biological sciences. Psychology
Haemophilus influenzae
Haemophilus Vaccines - immunology
Haemophilus Vaccines - pharmacology
Immunoglobulin G - biosynthesis
Immunoglobulin G - blood
Mice
Mice, Inbred Strains
Microbiology
Neisseria meningitidis - immunology
Polysaccharides, Bacterial - immunology
porin
Porins
Rats
Rats, Sprague-Dawley
Recombinant Proteins - biosynthesis
Recombinant Proteins - genetics
Recombinant Proteins - immunology
Tetanus Toxoid - pharmacology
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies
Vaccines, Conjugate - pharmacology
title Preclinical studies on a recombinant group B meningococcal porin as a carrier for a novel Haemophilus influenzae type b conjugate vaccine
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