Antibody neutralization of HIV-1 and the potential for vaccine design

Neutralisation by antibody is, for a number of viruses, an in vitro correla te for protection in vivo. For HIV-1 this is controversial. However, the in duction of a potent anti-HIV neutralising antibody response remains one of the principal goals in vaccine development. A greater knowledge of the fund amental mechanisms underlying the neutralisation process would help direct research towards suitable vaccine immunogens. The primary determinant of HI V neutralisation appears to be antibody affinity for the trimeric envelope glycoprotein spike on the virion, suggesting that epitope-specific effects are secondary and implying a single, dominant mechanism of neutralisation. Antibody interference with virion attachment to the target cell appears to be a major mechanism of neutralisation by gp120-specific antibodies. This i s probably achieved both by antibody-induced dissociation of gp120 from gp4 1 and by direct inhibition of virus binding to receptor-coreceptor complexe s. A gp41-specific antibody neutralises by interfering with post-attachment steps leading to virus membrane fusion. Recent advances in structural anal yses of the HIV envelope glycoproteins coupled with data obtained from anti body mapping and neutralisation studies allow a greater understanding of En v function and its inhibition. This in turn should lead to a more rational basis for vaccine design aimed at stimulating highly effective neutralising antibodies. (C) 1999 Elsevier Science B.V. All rights reserved.