A RECOMBINANT PRIME, PEPTIDE BOOST VACCINATION STRATEGY CAN FOCUS THEIMMUNE-RESPONSE ON TO MORE THAN ONE EPITOPE EVEN THOUGH THESE MAY NOTBE IMMUNODOMINANT IN THE COMPLEX IMMUNOGEN

Rhesus monkeys were successfully vaccinated using a strategy of primin g with a candidate envelope subunit vaccine and boosting with syntheti c peptides. Priming was carried out with recombinant HIV-1 SF2 envelop e glycoprotein incorporated into ISCOMs, following the attachment of a lipid tail. Peptides, covalently linked to ISCOMs, representing linea r sequences within the V2 and V3 regions, were used to boost functiona l antibodies to neutralizing epitopes in both of these regions. Inject ions with these peptide formulations substantially increased the titre of serum neutralizing antibodies from low or undetectable levels. In addition to completely neutralizing the homologous HIV-1 SF2 strain, t hese sera also neutralized the escape variant, HIV-1 SF13. However, no antibodies were boosted which could compete with human, neutralizing monoclonal antibodies recognising conformational epitopes. The peptide s also boosted antibodies to a peptide whose sequence lies close to th e V2 region neutralizing epitope but does not overlap with it. Importa ntly, the level of antibodies to an unrelated epitope associated with enhancement of HIV-1 SF13 continued to fall after the peptide boost. S uccessful protection against challenge with chimeric simian immunodefi ciency virus expressing HIV-1 SF13 envelope glycoproteins (SHIV SF13) may be due to an increase in the ratio of neutralizing to enhancing an tibodies by selectively boosting with peptides to critical neutralizin g epitopes. (C) 1997 Elsevier Science Ltd.