IMMUNOGENICITY OF RECOMBINANT INFLUENZA-VIRUS HEMAGGLUTININ CARRYING PEPTIDES FROM THE ENVELOPE PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

Haemagglutinin (HA), the major surface glycoprotein of influenza virus , is a potent immunogen against which viral neutralizing antibodies ar e directed. Studies of the three-dimensional structure of HA have iden tified major antigenic sites on the molecule. We have exploited HA as a carrier for small antigenic regions (epitopes) of the HIV-1 envelope (env) glycoprotein. Using recombinant DNA techniques, the epitopes we re inserted in-frame into a known antigenic site of HA to produce HA-e pitope chimeras. Guinea-pigs and mice immunized with these chimeras in combination with adjuvant generated significant immune responses agai nst the carrier HA and also produced epitope-specific antibodies that recognized the native whole HIV-1 env. One of the chimeras which conta ined a V3-loop sequence of HIV-1 env elicited neutralizing antibodies against the homologous strain of HIV-1. The antibodies against HA and the inserted epitopes remained at high levels for up to 72 weeks. Rema rkably, these responses were generated with low doses of immunogens co ntaining only nanogram quantities of the inserted epitopes. These resu lts suggest the utility of HA as a carrier to allow selective antibody induction against foreign epitopes, and offer a new approach for vacc ine development as well as for the production of monospecific antibodi es useful in diagnostics and research.