CTL-BASED VACCINES FOR THE AIDS VIRUS

Project: Research project

Project Details

Description

DESCRIPTION: (Adapted from Applicant's Abstract) Finding a vaccine for HIV is
one of the most pressing biomedical priorities today. After infection with HIV,
enormous virus replication occurs and the decline of this replication coincides
with a peak in HIV specific cytotoxic T lymphocytes (CTLs). Antibody responses
do not appear until later in the course of the disease. It is thought,
therefore, that this CTL response controls viral replication and, thus, it is
becoming increasingly clear that a HW vaccine must induce strong CTL responses.
In this proposal we will determine the role of CTL in control of viral
replication using the SIV-infected rhesus macaque as an animal model for
HW-infected humans. We will generate strong CTL responses in the absence of any
other SIV-specific immune responses and then challenge the vaccinated animals
with SIV. We have already immunized rhesus macaques with DNA and Modified
Vaccinia Ankara (MVA) encoding a single relevant CTL epitope and have generated
the strongest CTL responses ever seen (1 of 5 CD8 positive fresh PBL specific
for the simian AIDS virus). In this proposal we will generate CTL against
multiple epitopes in several different SIV proteins. Additionally, we will
induce Cm at mucosal sites. This will allow us to test the hypothesis that CTL
can ameliorate the course of disease after infection. To carry out these
studies we have assembled a team of investigators to fully utilize this animal
model. Ashley Haase and Steve Wolinsky will determine the nature of virus
replication in situ and the evolution of quasi species, respectively. Yoshi
Kawaoka will construct chimeric influenza viruses for induction of CTL at
mucosal sites. Chris Miller will infect immunized rhesus macaques
intravaginally (IVAG) with a well-defined stock of SIVmac25 1. John Altman will
synthesize MHC class I tetramers for CTL quantitation and Deborah Fuller will
immunize animals using the gene gun.
StatusFinished
Effective start/end date9/1/996/30/05

Funding

  • National Institute of Allergy and Infectious Diseases: $412,690.00
  • National Institute of Allergy and Infectious Diseases: $440,507.00
  • National Institute of Allergy and Infectious Diseases: $435,384.00
  • National Institute of Allergy and Infectious Diseases: $369,168.00
  • National Institute of Allergy and Infectious Diseases

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