PRECLINICAL STUDIES ON A RECOMBINANT GROUP-B MENINGOCOCCAL PORIN AS ACARRIER 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) polyribosylr ibotol phosphate (PRP) conjugate vaccine. The use of rPorB may avoid u ndesirable immunologic interactions among vaccine components, includin g epitopic suppression from conventional carriers (e.g. tetanus toxoid [TT]), as well as provide desirable immunomodulatory effects. Rats we re found to be more reliable and consistent than mice or guinea pigs f or studying antibody responses to the Hib conjugates. Different Hib co njugates, Hib-TT and Hib-rPorB, consisting of PRP conjugated by reduct ive amination to TT or rPorB, were compared in rats. Commercially avai lable, licensed vaccines, HbOC (HibTITER(R)) and PRP-T (OmniHIB(R)), w ere used as reference controls. Maximum geometric mean ELISA IgG titer s were obtained in rats after only two doses, showing booster effects for all. However, Hib-rPorB immunization consistently resulted in resp onses that were 1-2 orders of magnitude greater than those for the oth er 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 adj uvant. These results warrant further investigation of Hib-rdPorB in co mbination with DTadP. (C) 1998 Elsevier Science Ltd. All rights reserv ed.