MHC DEFINED AND MHC IDENTICAL PRIMATES FOR AIDS RESEARCH

Project: Research project

Project Details

Description

DESCRIPTION (adapted from the application): Progress toward the development
of a vaccine for HIV has been hindered by the limited number of animal
models with which to study HIV infection of humans. Simian immunodeficiency
virus (SIV) infection of the rhesus macaque is an accepted animal model for
HIV infection of humans. Although several vaccines tested in rhesus
macaques have provided protection against SIV challenge, it has not been
possible to determine the correlates of protection in these vaccine trials.
There is a strong cytotoxic T lymphocyte (CTL) response to the AIDS virus in
both human and rhesus macaques, and CTLs have been implicated in providing
protection from infection. Understanding the role of CTLs in AIDS
virus-induced disease will be important for the design of effective
vaccines. Few CTL epitopes have been defined in SIV and there are no inbred
strains of rhesus macaques for CTL adoptive transfer studies. The
investigators propose to triple the number of defined SIV CTL epitopes and
to develop a rapid MHC class I-typing of rhesus macaques. They propose to
find two new epitopes for env and four for nef. These will be characterized
for anchor residues, minimal recognizable peptide and MHC class I molecules
that bind these epitopes. A PCR-SSP-based technique will be developed for
detecting nine restricting rhesus macaque MHC class I alleles. They will
produce pairs of MHC-identical rhesus macaques to explore the role of CTLs
in AIDS virus infection. This will be done by survey of macaque pedigrees.
Female relatives of SIV-infected monkeys will provide ova for in vitro
fertilization and nuclear transfer for production of pairs of identical
twins. They will produce additional pairs of MHC-defined, identical rhesus
macaques for CTL adoptive transfer studies to study correlates of immune
protection.
StatusFinished
Effective start/end date9/30/979/29/99

Funding

  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases

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