Characterization of primary isolate-like variants of simian-human immunodeficiency virus

Several different strains of simian-human immunodeficiency virus (SHIV) tha t contain the envelope glycoproteins of either T-cell-line-adapted (TCLA) s trains or primary isolates of human immunodeficiency virus type 1 (HIV-1) a re now available. One of the advantages of these chimeric viruses is their application to studies of HIV-1-specific neutralizing antibodies in preclin ical AIDS vaccine studies in nonhuman primates. In this regard, an importan t consideration is the spectrum of antigenic properties exhibited by the di fferent envelope glycoproteins used for SHIV construction. The antigenic pr operties of six SHIV variants were characterized here in neutralization ass ays with recombinant soluble CD4 (rsCD4), monoclonal antibodies, and serum samples from SHIV-infected macaques and HIV-1-infected individuals, Neutral ization of SHIV variants HXBc2, KU2, 89.6, and 89.6P by autologous and hete rologous sera from SHIV-infected macaques was restricted to an extent that these viruses may be considered heterologous to one another in their major neutralization determinants. Little or no variation was seen in the neutral ization determinants on SHIV variants 89.6P, 89.6PD, and SHIV-KB9, Neutrali zation of SHIV HXBc2 by sera from HXBc2-infected macaques could be blocked with autologous V3-loop peptide; this was less true in the case of SHIV 89. 6 and sera from SHIV 89.6-infected macaques, The poorly immunogenic but hig hly conserved epitope for monoclonal antibody 1gG1b12 was a target for neut ralization on SHIV variants HXBc2, KU2, and 89.6 but not on 89.6P and KB9, The 2G12 epitope was a target for neutralization on all five SHIV variants. SHIV variants KU2, 89.6, 89.6P, 89.6PD, and KB9 exhibited antigenic proper ties characteristic of primary isolates by being relatively insensitive to neutralization in peripheral blood mononuclear cells with serum samples fro m HIV-1-infected individuals and 12 fold to 38-fold less sensitive to inhib ition with recombinant soluble CD4 than TCLA strains of HIV-1. The utility of nonhuman primate models in AIDS vaccine development is strengthened by t he availability of SHIV variants that are heterologous in their neutralizat ion determinants and exhibit antigenic properties shared with primary isola tes.