High-titer HIV-1 neutralizing antibody response of rhesus macaques to gp160 and env peptides.

Abstract

Three groups of four rhesus macaques were immunized twice, one month apart with purified recombinant HIV-1LAI gp160 in the presence of either alum, incomplete Freund's adjuvant (IFA), or SAF-1. Two months later, the animals were injected twice again with a synthetic peptide with the sequence of the principal neutralization determinant (PND) of the HIV-1LAI isolate mixed with the same adjuvants. All animals received a booster injection of gp160 and PND peptide at 6 months. This regimen of immunization induced in the SAF-1 and IFA groups a high-titer neutralizing antibody response that declined progressively over the course of the following 6 months. In contrast, only a weak response was observed in the alum group. Neutralizing antibody titers varied as anti-PND titers, suggesting that they were principally targeted to the PND. A shortened immunization protocol comprising two injections of gp160 at 0 and 1 month followed by one injection of PND peptide at 3 months is suggested as optimal for the induction of high titers of HIV-1 neutralizing antibodies in primates.