RESTRICTED SPECIFICITY OF ANTI-V3 ANTIBODIES INDUCED IN HUMANS BY HIVCANDIDATE VACCINES

We analyzed the fine specificity of anti-V3 antibodies elicited in thr ee different species (human, guinea pig, and macaque) by various HIV c andidate vaccines, Following immunization with recombinant canarypox v irus expressing gp160MN or with recombinant gp160MN/LAI, this antibody response was shown to be directed against the NH2-terminal region of the V3 loop, Although this response was increased by a prime-boost reg imen using immunization with canarypox expressing gp160 followed by an rgp160 boost, its specificity remained restricted mainly to the recog nition of this region of the V3 loop, Pepscan analysis of sera confirm ed the results obtained by ELISA and allowed the definition of an immu nodominant common binding site for these sera located within the seque nce NKRKRIHIGPGR. In contrast to these results, a boost with the V3 pe ptide was shown to broaden the antibody response and pepscan analysis showed that sera from individuals boosted with the V3 synthetic peptid e recognize determinants all along the V3 loop, Similar fine specifici ty of anti-V3 antibodies was obtained in human, guinea pig, and macaqu e following immunization by a prime-boost regimen using canarypox reco mbinants expressing gp160 or gp120 and purified rgp160, In contrast, a V3 synthetic peptide boost stimulated the production of antibodies th at recognize multiple epitopes within the V3 loop, Because the inducti on of antibodies that recognize multiple sites in the V3 loop could be of major importance to neutralize different HIV isolates, these resul ts may have implications for the design and selection of HIV candidate vaccines.