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

被引:19
作者
Fusco, PC [1 ]
Michon, F [1 ]
Laude-Sharp, M [1 ]
Minetti, CASA [1 ]
Huang, CH [1 ]
Heron, I [1 ]
Blake, MS [1 ]
机构
[1] N Amer Vaccine Inc, Beltsville, MD 20705 USA
关键词
Haemophilus influenzae; porin; conjugate;
D O I
10.1016/S0264-410X(98)00174-1
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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(R)) and PRP-T (OmniHIB(R)), 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-rdPorB in combination with DTadP. (C) 1998 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:1842 / 1849
页数:8
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