The development and evaluation of HIV vaccines

Abstract

Experimental simian immunodeficiency virus and human immunodeficiency virus (HIV) vaccines have been shown to induce protective immunity in macaques and chimpanzees, respectively. Immunologic correlates of protection have not been established, although in the case of HIV vaccines, gp120-, V3-specific neutralizing antibodies may be involved. V3 sequences are strain specific, and the genetic and antigenic variability of HIV may present an obstacle for vaccine development. However, in addition to anti-V3 antibodies, the immune response to HIV infection (and immunization) involves group-specific neutralizing antibodies directed against conformational epitopes in the gpl20-CD4 binding site, as well as an array of cell-mediated immune responses against several HIV proteins. Safety and immunogenicity human trials (Phase l/ll) of 12 candidate vaccines tested in HIV-negative volunteers have shown that, in general, they are well tolerated and induce neutralizing antibodies and different cell-mediated responses. Safety and immunogenicity trials of four candidate vaccines in HIV-infected volunteers have shown that they are safe and capable of increasing anti-HIV immune responses, although no information has been obtained on potential clinical benefits. Criteria for initiating efficacy (Phase III) trials of preventive candidate vaccines are being discussed by the scientific community, and appropriate study populations are being identified and prepared by industrialized and developing countries through collaboration with the World Health Organization and other national and international HIV vaccine research programs.