Induction of inhibitory antibodies to the CCR5 chemokine receptor and their complementary role in preventing SIV infection in macaques

The seven-transmembrane G-protein-linked CCR5 molecule functions as a major coreceptor for HIV or simian immunodeficiency virus (SIV) infection. Antib odies to CCR5 were studied in rhesus macaques immunized with SIV grown in h uman CD4(+) T cells. These macaques were completely protected against i.v. challenge with live SIV. Sera from the protected macaques showed significan tly greater inhibition of SIV replication (p < 0.001) and macrophage inflam matory protein-1 beta-generated CCR5-dependent chemotaxis (p < 0.01) than s era from unprotected macaques, in the absence of significant neutralizing a ntibodies to SIV. These two functional assays demonstrate serum antibodies to the CCR5 receptors which were specifically inhibited by CCR5-transfected HEK-293 cells. We postulate that anti-CCR5 antibodies may be complementary to beta-chemokines in blocking CCR5 coreceptors to HIV or SIV binding and fusion of CD4(+) cells.