MOLECULAR APPROACHES FOR DEVELOPMENT OF AN HIV VACCINE--RHESUS MACAQUES MODEL

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In the last year particular emphasis has been placed only in vaccine approaches involving attenuated poxviruses (NYVAC) and avipox (ALVAC). Partial protection was observed in rhesus macaques vaccinated with NYVAC- or ALVAC-human immunodeficiency virus type 2 (HIV-2) against a live intravenous HIV-2 challenge. Similarly, NYVAC or ALVAC HIV-I-immunized animals were partially cross-protected against an HIV-2 challenge. In a study initiated five years ago, NYVAC/simian immunodeficiency virus (SIV)-vaccinated animals, although infected upon viral challenge, demonstrated longer survival than the control animals, and two of them have progressed to AIDS two years after infection (all controls died within two years from infection). Taken together these studies suggested that the longer the time of immunization, the better. Seven months ago two studies were started. The first study involved 44 rhesus macaques. The protocol was designed to study the modulatory effect of interleukins such as interleukin 2 (IL-2) and IL-12 on the immunogencity of NYVAC SIV gag, pol, and env vaccine. At the end of the immunization period (18 months) one-half of the animals will be challenged intravenously and one-half mucosally with live SIV(251). The second study in chimpanzees aims to separately evaluate, in a controlled manner, the efficacy of ALVAC and NYVAC HIV-1 recombinant vaccines. A parallel study using NYVAC- and ALVAC-human T-cell leukemia/ lymphotropic virus type I env vaccines in a rabbit model has provided encouraging results on the possibility of inducing sterilizing immunity against a human retrovirus. Some effort has been devoted in investigating the role of human herpesvirus 6 as a pathogen in a pigtail macaque model using an SIV isolate with low pathogenicity.