Vaccines directed against HIV: preventive and therapeutic strategies

Vaccine therapy studies in HIV-seropositive volunteers over the next year should provide additional insights into whether different vaccine viral strains (LAI, IIIB, MN, SF2), different protein sources (whole virus particles, recombinant protein, peptides), different expression systems (baculovirus, mammalian), or different adjuvants (incomplete Freund's, MTP-PE, MF59, alum) generate significantly different immune responses at the cellular and humoral level. In addition, differences in the ability of each vaccine to induce humoral immune responses to epitopes in the constant regions vs. variable regions, contiguous or noncontiguous "conformational" epitopes, with high vs. low antibody affinity can be evaluated. The roles of antibody-dependent cellular cytotoxicity (ADCC), cellular recognition, nonspecific natural killing, and MHC-restricted cytotoxicity can also be explored. To date, the majority of the immunogens have proven to be safe. Many induce new humoral and cellular immune responses against HIV. The final important question remains, whether any of these vaccines used as therapeutic immunogens generate immune responses that induce an altered disease course with a prolonged asymptomatic period without immunodeficiency, whether vaccines can affect increased viral clearance, or decreased transmission/infectivity? There remains no in vitro assay known to correlate with lack of disease progression, no immune profile consistent with a prolonged asymptomatic period. The vaccine therapy trial researchers seek the answers to these important questions. No single research organization can begin to address all the possibilities, so the overall pace of exploration of this therapeutic concept is likely to be dictated by the level of cooperation between the many groups involved in these studies. Open collaboration between researchers and open exchange of reagents, immunogens for in vitro experiments, and sera will allow faster dissection of the many questions and issues raised in this chapter. Whether vaccine therapy proves to have a useful role in the treatment of HIV-1-induced disease, these studies will ultimately lead to the development of useful techniques and provide new insights into the nature of the immunological responses, as the investigation of vaccine therapy did over a century ago.