SIV IN MACAQUES IS A MODEL FOR AIDS VACCINE DEVELOPMENT

  • Yilma, Tilahun (PI)

Project: Research project

Project Details

Description

Experimental transmission of SIv to ASian macaque monkeys (rhesus)ns of,
induces a fatal immunodeficiency disease which resembles AIDS in humans
infected with HIV-1 or HIV-2. Thus, SIV infection of rhesus macaques
offers a highly manipulatable animal lentivirus system that can be used
to analyze pathogenesis and to test and develop strategies that inhibit
virus replication and prevent disease. We will pursue the hypothesis
that the SIV animal model can be used to elucidate principles that will
guide testing and development of safe and effective anti-HIV vaccines. SPECIFIC AIM 1: Immunologic correlates of protective immunity will be
identified. Comparative studies of immune responses of rhesus macaques
infected with molecularly cloned SIVmac and uncloned SIVmac will be
pursued to determine if differences in the clinical outcome of infection
can be accounted for by the host immune response. These investigations
will also examine effects of viral sequence variation on immune
responses. SPECIFIC AIM 2. Functional and immunological domains of the SIV envelope
glycoprotein will be defined by characterizing envelope gene variants
generated by site-directed mutagenesis. SPECIFIC AIM 3. Vaccinia viruses expressing envelope genes of selected
SIV variants and lymphokines, will be tested in rhesus macaques for
induction of anti-viral immune responses and for protection against
challenge with virulent SIV. SPECIFIC AIM 4. Recombinant SIV antigens, produced in genetically
engineered yeast and mammalian cells, will be evaluated with respect to
immune responses and resistance to challenge. SPECIFIC AIM 5. Macaques immunized with candidate SIV mac vaccines will
be challenged by exposure of genital mucosa to a minimal infectious dose
of cell-associated virus and cell-free virus. Results from specific Aids 1 and 2 on host immune responses and SIv
strain variation will be relevant both for vaccine development and for
understanding pathogenesis. The vaccinia vector systems in together with
recombinant SIV antigens will be used to focus on immune responses to
individual viral proteins; these materials will be essential for
elucidating immune responses that may correlate with protective
immunity. Additional important objectives in this proposal include
standardization of assay for measuring anti-viral immune responses and
for monitoring virus (i.e., detection of viral nucleic acid by
polymerase chain reaction amplification). The research in this proposal
may establish a procedure to achieve protective immunity in a non-human
primate model against an immunosuppressive lentivirus. These results may
be applicable for developing vaccination procedures to protect humans
against HIV-1 infection and disease.
StatusFinished
Effective start/end date9/30/897/31/95

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)

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