Evaluation of constructed recombinant mengoviruses and other HIV vaccine candidates in murine and primate models
Van der Ryst, Elna
MetadataShow full item record
The development of an effective vaccine against HIV is a formidable challenge. The overall objective of this work was to evaluate different HIV -1 vaccine approaches in primate and murine models. In a first approach recombinant Mengoviruses expressing several HIV -1 and SIV gene products were evaluated for their immunogenicity in mice and macaques. Results indicated that Mengovirus recombinants expressing HIV -1 Nef or SIV CTL epitopes are weak immunogens. This was disappointing in light of the promising results previously obtained using other Mengovirus recombinants and indicated that the nature of the insert might play an important 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 genes was evaluated. In animals challenged by the iv route protection from homologous challenge was seen in one of two animals and this correlated with the neutralising antibody levels. One of five females resisted a total of 3 vaginal challenges, while two further animals resisted 2 challenges. However, only low levels of HIV-l-specific neutralising antibodies were present at time of challenge. This suggests that neutralising antibodies may have little importance for protection from mucosal infection in chimpanzees, in contrast with what was seen for iv challenge. Finally, macaques were immunised with a primary isolate of HIV -1 in order to evaluate the breadth of the immune response induced by HIV-1 in its "native" state. The animals 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 -1BX08 were demonstrated, and sera From the animals induced strong facilitation of HIV -1 replication in PBMC, raising the concern that whole virus based HIV vaccines might induce facilitating antibodies that can result in Facilitation of transmission and/or evolution of disease.