Evaluation of constructed recombinant mengoviruses and other HIV vaccine candidates in murine and primate models

[摘要] The development of an effective vaccine against HIV is a formidable challenge. The overallobjective of this work was to evaluate different HIV -1 vaccine approaches in primate andmurine models. In a first approach recombinant Mengoviruses expressing several HIV -1 andSIV gene products were evaluated for their immunogenicity in mice and macaques. Resultsindicated that Mengovirus recombinants expressing HIV -1 Nef or SIV CTL epitopes are weakimmunogens. This was disappointing in light of the promising results previously obtainedusing other Mengovirus recombinants and indicated that the nature of the insert might play animportant role in the immunogenicity of Mengovirus recombinants. As a second approach,protection of chimpanzees from intravenous and vaginal challenge by immunisation with a recombinant canarypox virus expressing the HIV-ll1lB/LAI gp 120rrM, gag and protease geneswas evaluated. In animals challenged by the iv route protection from homologous challengewas seen in one of two animals and this correlated with the neutralising antibody levels. Oneof five females resisted a total of 3 vaginal challenges, while two further animals resisted 2challenges. However, only low levels of HIV-l-specific neutralising antibodies were presentat time of challenge. This suggests that neutralising antibodies may have little importance forprotection from mucosal infection in chimpanzees, in contrast with what was seen for ivchallenge. Finally, macaques were immunised with a primary isolate of HIV -1 in order toevaluate the breadth of the immune response induced by HIV-1 in its native state. Theanimals developed moderate to high titers of total anti-HIV -1 antibodies as measured by EIA, which was mainly Gag directed. However, no antibodies capable of neutral ising HIV -1BX08were demonstrated, and sera From the animals induced strong facilitation of HIV -1 replicationin PBMC, raising the concern that whole virus based HIV vaccines might induce facilitatingantibodies that can result in Facilitation of transmission and/or evolution of disease.

[发布机构] University of the Free State