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168 Prevention of Disease Induced by Heterologous SHIV Challenge in Rhesus Monkeys Using a Multicomponent Subunit AIDS Vaccine
P. Vandepapeliere*1, K. Manson2, P. Mooij3, D. Montefiori4, D. Watkins5, J. Heeney3, M. Wyand2, J. Cohen1, C. Bruck1, and G. Voss1
1GlaxoSmithKline Biologicals, Rixensart, Belgium; 2Primedica, Worcester, MA, USA; 3Biomedical Primate Res. Ctr., Rijswijk, The Netherlands; 4Duke Univ. Med. Ctr., Durham, NC, USA; and 5Wisconsin Regional Primate Res. Ctr., Madison, USA
A multiantigen AIDS vaccine comprising gp120 and recombinant regulatory HIV proteins has been developed and tested in the rhesus monkey SHIV challenge model. The vaccine contains gp120, Nef and Tat, together with the potent adjuvant AS02A. The antigen components were evaluated separately and in combination in groups of 4 animals. Control animals received the adjuvant without antigen. After 3 immunizations the study animals were subjected to an intravenous challenge with the chimeric, highly pathogenic and partially heterologous SHIV89.6p. Analysis of plasma virus load and virus-infected cells revealed that all study animals became infected with SHIV. Three out of 4 control animals experienced a precipitous drop in CD4-positive cells, maintained a high virus load, and eventually had to be euthanized due to the development of AIDS-related illness. The groups of animals having received the single component vaccines showed a similar outcome as the control group. However, all animals being immunized with the combination of gp120 and regulatory protein antigens maintained their CD4 cell counts and the virus load increase post challenge was transient and rapidly dropped to sustained undetectable levels. Furthermore, more than 18 months after virus challenge all animals are still alive. A second study in a genetically unrelated monkey population that was less susceptible to disease manifestations after SHIV challenge has confirmed the maintenance of CD4-positive cells in animals immunized with the combination vaccine. These data suggest that the combination vaccine can control efficiently the replication of the virus and the development of disease in the infected nonhuman primate host. They have potentially important implications for the development of both prophylactic and therapeutic vaccines Therefore, this candidate AIDS vaccine will enter into clinical trials in the near future.
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