A conformational C4 peptide polymer vaccine coupled with live recombinant vector priming is immunogenic but does not protect against rectal SIV challenge

The conserved, immunogenic CD4 binding site on the viral envelope is an att ractive HIV or SIV vaccine candidate. Polymerization of an 18 amino acid se gment derived from the C4 domain of SIV gp120 produced a peptide polymer or "peptomer," having an alpha -helical conformation possibly mimicking a pro posed structure of the C4 domain in the unbound native protein. The SIV pep tomer and native gp120 were compared as subunit boosts following two adenov irus type 5 host range (Ad5hr)-SIVenv recombinant priming immunizations. Bo th vaccine regimens successfully elicited SIV-specific CTL responses in fiv e of six immunized macaques. Peptomer-boosted macaques exhibited significan tly higher envelope-specific T cell proliferative responses than either the gp120-boosted macaques or controls. Peptomer immunization also elicited pe ptomer and SIV gp120-specific binding antibodies, but only native gp120 boo sting elicited SIV neutralizing antibodies. Upon intrarectal challenge with SIVmac32H, all nine macaques became infected. The solely envelope-based va ccine conferred no protection. However, changing the boosting immunogen to the C4 peptomer did not improve protective efficacy in spite of its elicita tion of humoral and cellular immune responses, including robust T-helper ac tivity. In spite of the peptomer's strong immunogenicity and potential for induction of broadly protective immune responses, it was not effective as a subunit vaccine.