PREVENTIVE AND THERAPEUTIC PEPTIDE AIDS VACCINES

Project: Research project

Project Details

Description

This project builds upon an existing program that has already generated
exciting results with a novel vaccine, based on multiple peptides derived
from the V3 domain of gp120 conjugated to PPD. Most notably, we observed
in animals the generation of high titered primary isolate neutralizing
antibodies and in HIV + vaccines major reduction in plasma HIV levels that
were correlated with substantial increases in titers of neutralizing
against V3 loop epitopes. This system utilizes the potent adjuvanticity of
PPD in BCG-preimmunized subjects and animals. Based on these observations
it appears that this vaccine has demonstrated more effectiveness than any
other HIV vaccine for which data have been reported. We believe that
despite difficulties in generating effective antibodies against env
regions in the past, these domains are in fact the major neutralizing
target in vivo. We now propose to expand this approach to 1) develop
improved V3 peptide and gp41 vaccine conjugates focusing on PPD and
various recombinant proteins of M. tuberculosis, 2) evaluate hypothesis
for the mechanisms of action of PDD as a unique vaccine carrier to allow
for improvement of conjugate immunogenicity. 3) Test the utility of V3
loop and gp41 peptide cocktail vaccines in the prevention of HIV infection
in animal models, including transgenic hu CD4/CCR5 mice, SCID-hu mice,
HIV+ chimpanzees and in limited clinical trials in HIV seronegative and
HIV + volunteers. We believe that this is a feasible approach towards the
development of effective HIV vaccines for preventative and therapeutic
purposes. Since our preliminary vaccine has already shown efficacy in a
small scale human clinical trials, additional experiments with this
vaccine can be done now. Moreover, the hypothesized improvements to the
vaccine realistically can be incorporated into the vaccine within a short
time.
StatusFinished
Effective start/end date1/1/016/30/99

ASJC

  • Infectious Diseases
  • Virology
  • Immunology

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