DEVELOPMENT OF AN HIV-1 AND HTLV-1 VACCINE IN ANIMAL MODELS

点击翻译按钮获取中文摘要

Efforts in the development of poxvirus-based vaccines to prevent HIV-I and HTLV-I infection are continuing. SIV model: A protocol designed to obtain preclinical data in the pathogenic SIV251 macaque model is ongoing. The protocol was designed to investigate the modulatory effect of interleukins such as interleukines 2 (IL-2) and 12 (IL-12) on the immunogenicity of NYVAC SIV gag, pol, and env vaccines The adjuvant effect of NYVAC-IL-2 and NYVAC-IL-12, at the time of immunization, was evidenced by a change in the vaccinees of the systemic immune response against viral antigens. Higher cellular immune responses, at the expenses of humoral immune responses, were measured in animals exposed to IL-12 at the time of immunization. Live SIV251 challenge was performed intravenously in half of the animals and intrarectally in the remaining half. Fifty percent of the animals in both groups were able to control acute viral infection. The immunological modulation induced by IL-2 and IL-12, however, did not correlate with the ability of the animals to control the acute viremia. The effect of these vaccine regimens in the clinical course of SIV infection remains to be investigated. Chimpanzee model: One year ago we started a protocol designed to compare the immunogenicity and efficacy of NYVAC and ALVAC HIV vaccines in chimpanzees. The animals have been immunized four times with recombinant poxvirus vectors carrying the gag, pol, env, and nef genes. The plan is to challenge these animals intrarectally with the chimpanzee-adapted HIV-IC499 isolate, which is being tested now for infectivity. HTLV-I in rabbits: Immunization and challenge experiments with NYVAC HTLV-I vaccines are aimed at defining the importance of various viral antigens as components of a vaccine formulation and the vaccination regimens. STLV-I in primates: At the Southwest Foundation a high prevalence of STLV-I infection and the development of T-cell lymphoma-infected baboons have been described. A collaborative effort has been initiated to eradicate STLV-I from this colony by vaccinating young baboons. Studies on the incidence of STLV-I infection in adults and maternal-fetal transmission have been initiated to define the cohort of animals to be vaccinated in a preliminary study. The advantage of the primate model is the possibility of testing vaccine efficacy in a natural setting of STLV-I transmission.