ADJUVANT IS REQUIRED WHEN USING ENV LIPOPEPTIDE CONSTRUCT TO INDUCE HIV TYPE 1-SPECIFIC NEUTRALIZING ANTIBODY-RESPONSES IN MICE IN-VIVO

Extensive immunological studies on HIV-1 infection, the causative agen t of AIDS in humans, have led to the conclusion that efficient protect ion against this infection should require early elicitation of neutral izing antibodies as well as cellular immune and particularly cytotoxic T lymphocyte responses. The use of synthetic peptides modified at one end by introduction of a lipidic tail is now well known to be an effe ctive means of eliciting virus-specific cytotoxic T lymphocyte respons es in vivo, both in mouse and humans, To ascertain that such a strateg y can be used for vaccinal purposes, particularly against HIV-1 infect ion, it remains to be determined whether these molecules can also act as effective inducers of antibody responses, most of all of the neutra lizing type, The present study set out to address this question by usi ng a synthetic HIV-1 ENV lipopeptide construct, previously identified as a potent immunogen for in vivo induction of ENV-specific CTL respon ses in BALB/c mice, We first showed that V3 peptide-specific antibodie s were effectively induced by the lipopeptide construct. However, we p rovided evidence that the biological activity of these antibodies, i,e ., their ability to neutralize HIV-1 infectivity in vitro, was strongl y influenced by the immunizing conditions and protocol, in that only t hose antibodies generated by the use of adjuvanted lipopeptide formula tions were effective. Albeit at a slightly lower efficacy than by the intraperitoneal route, neutralizing antibodies could also be induced u sing the subcutaneous route. With the prospect of a human peptide vacc ine in mind, we then studied the properties of different known or poss ibly clinically relevant adjuvants, We found that alum, the only relev ant adjuvant for human use, not only provides inefficient help to the lipopeptide construct in generating neutralizing antibodies, but tends to have deleterious effects on the ability of the construct to induce CTL responses, The only protocol that gave satisfactory results in te rms of the magnitude of the neutralizing antibody responses was a mine ral oil-based lipopeptide formulation. When induced under those condit ions, strong neutralizing activities were still present up to 8 months after the last injection.