Human immunodeficiency virus type 1 (HIV-1) envelope vaccines can now be evaluated for efficacy in macaques by challenging with chimeric viruses in which the env, tat and rev genes of simian immunodeficiency virus (SIV) have been replaced by those of HIV-1. Most experiments have so far been conducted using gp120 molecules derived from T-cell-adapted LAI or MN strains of HIV-1, which predominantly use the CXCR-4 co-receptor. These vaccines protect against infection by apathogenic chimeric virus carrying the same envelope sequences. In the experiment described here, four macaques were vaccinated with W61D gp120 derived from a low passage Dutch isolate and capable of inhibiting the binding of MIP1beta to the co-receptor CCR-5. This vaccine was potent, inducing high titres of binding and neutralizing antibodies against the homologous HIV-1 and tenfold lower titres against a heterologous challenge virus (SHIV(SF33)) in which the env, tat and rev genes of SIV had been replaced by those of a San Francisco isolate, HIV-1(SF33). Despite strong immune responses to the vaccine there was no evidence that it protected against challenge with this chimeric virus. The antigenic divergence between vaccine and challenge virus or the increased virulence of the challenge virus may be responsible for the inability of this vaccine to protect against infection by SHIV(SF33).


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