Evaluation of constructed recombinant mengoviruses and other HIV vaccine candidates in murine and primate models
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Date
2001-03
Authors
Van der Ryst, Elna
Journal Title
Journal ISSN
Volume Title
Publisher
University of the Free State
Abstract
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.
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Keywords
AIDS (Disease), Vaccines, Thesis (Ph.D. (Medical Microbiology))--University of the Free State, 2001