A successful prophylactic human immunodeficiency virus type 1 (HIV-1)
vaccine must elicit an immune response that will prevent establishment
of the persistent viral infection. The only response shown to be effe
ctive in this regard is virus-neutralizing antibody directed against t
he viral gp120 hypervariable V3-loop region. Conjugate immunogens, con
taining cyclic peptides representing the V3 determinant covalently bou
nd to a carrier protein, were capable of eliciting virus-neutralizing
antibodies. The consistency of the response was related to peptide siz
e. The smaller cyclic peptides, expressing relatively conserved sequen
ces from the V3-loop apex, were poor inducers of neutralizing activity
. In contrast, the largest cyclic peptides mediated neutralizing respo
nses that were similar to those observed and previously reported for i
ntact gp120 immunogens. A cyclic synthetic peptide expressing most of
the prototypic HIV-1 MN variant V3 determinant warrants further study
as a potentially effective vaccine immunogen.