EBV/SIV CHIMERA VECTORS FOR AIDS VIRUS VACCINATION

Project: Research project

Project Details

Description

DESCRIPTION (adapted from applicant's abstract): Simian immunodeficiency
virus (SIV) infection of macaques provides the best non-human primate model
for studying AIDS. We will utilize the SIV/macaque model to determine
whether Epstein Barr virus (EBV) can be used as a vector to generate strong
immune responses to SIV in vivo. It has been difficult to devise an
effective vaccine for human immunodeficiency virus (HIV). Live attenuated
SIV has protected rhesus macaques from subsequent challenge with pathogenic
strains of SIV. However, questions concerning the safety of this live
vaccine still remain. Since HIV and EBV share many similar characteristics,
we propose to use EBV as a live virus vector for generating SIV-specific
responses. We will use both EBV-transformed B Lymphocyte cell lines (BLCL)
stably transfected with SIV genes and mini-EBV vectors expressing SIV genes
to immunize rhesus monkeys.

In many respects, EBV and the HIV share several important characteristics.
Both of these viruses cause a massive T-cell proliferative response upon
infection. This is especially evident in the CD8+ subset of T cells, and
there is some evidence to suggest that both of these viruses induce an
antigen-specific response within the first month after infection. There is
also evidence that CD8+ cytotoxic T lymphocytes (CTL) provide some kind of
protection against infection with both of these viruses. Individuals that
have been previously infected with EBV will occasionally exhibit EBV-induced
tumors if they are immunosuppressed. Withdrawal of the immunosuppression
normally results in disappearance of the tumors. EBV and HIV are also
persistent lymphotropic viruses. That is, after the initial round of
replicative activity, both of these viruses assume a quiescent state within
the immune system. These similarities between EBV and HIV make the use of
EBV as a vector to deliver HIV genes an excellent candidate for inducing
strong immune responses. The fact that EBV infected-B cells home to the
lymph nodes suggests that EBV would be an excellent live virus vector for
HIV. In this proposal, we will develop EBV based vectors to use as AIDS
virus vaccines using the rhesus monkey as an animal model to test these
vaccines.

In Specific Aim I we will test the hypothesis that transfection of
EBV-transformed autologous BLCL with vectors expressing SIV genes can be
used to generate a strong AIDS-virus specific immune response in MHC defined
animals. In Specific Aim II, we will test the hypothesis that a mini-EBV
vector expressing SIV genes can be used to generate an AIDS-virus specific
immune response in MHC-defined animals.
StatusFinished
Effective start/end date2/1/981/31/01

Funding

  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases: $62,000.00
  • National Institute of Allergy and Infectious Diseases

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