LIVE ATTENUATED MULTIPLY DELETED HIV-1 VACCINE FOR AIDS

  • Desrosiers, Ronald Charles (PI)
  • Wyand, Michael (PI)
  • Walker, Bruce (PI)
  • Neutra, Marian (PI)
  • Johnson, R. Paul (PI)
  • Walker, Bruce (PI)
  • Desrosiers, Ronald (PI)
  • Wyand, Michael (PI)

Project: Research project

Description

OVERALL DESCRIPTION This application was
submitted by Dr. Ronald C. Desrosiers in response to RFA AI-93-04 and
proposes establishment of a National Cooperative Vaccine Development
Group for AIDS (NCVDG). The proposed studies are centered around a
radical but promising strategy for the development of a vaccine against
HIV: the construction of a live-attenuated, multiply-deleted HIV-1
vaccine for prevention of infection and disease, using modern
recombinant DNA technology to delete large regions of genetic
information from the virus. Preliminary studies using the SIV/rhesus
monkey model indicate that a singly-deleted variant missing the nef gene
is both safe and highly effective. Major advantages of a live-
attenuated, multiply-deleted HIV-1 vaccine for AIDS include very low cost
of production, worldwide availability, and the likelihood that this will
be the most effective vaccine that can be made. In the proposed
studies, optimal combinations of deletions that balance safety and
potency will be identified, immunological components responsible for
protection will be examined, and a variety of safety and efficacy issues
will be addressed. The proposal is divided into 3 Projects plus an Administrative and
Scientific Core. PROJECT I (Desrosiers) deals with construction of
multiply-deleted SIV and HIV-1 variants, characterization of their
biological properties in vitro, and evaluation of their safety and
efficacy in the rhesus macaque and chimpanzee models. PROJECT II
(Walker) focuses on defining the cellular immune responses to live-
attenuated vaccines, emphasizing CTL activity. PROJECT III (Wyand) is
designed to test safety and efficacy under increasingly rigorous
challenge conditions and various immunization schemes. The Core will
provide administrative support and scientific services, including
assistance in preparing and storing virus stocks, purifying virus,
preparing ELISA plates, quality control and performing neutralization
assays.
StatusFinished
Effective start/end date2/15/947/31/05

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $2,158,944.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $2,168,168.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $1,995,113.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $2,135,845.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $2,243,025.00
  • National Institutes of Health

Fingerprint

AIDS Vaccines
Safety
Vaccines
HIV-1
SAIDS Vaccines
Attenuated Vaccines
Viruses
Walkers
Acquired Immunodeficiency Syndrome
Pan troglodytes
HIV
Macaca mulatta
Cellular Immunity
Quality Control
Technology
Immunization
nef Genes
Enzyme-Linked Immunosorbent Assay
Infection
Immunity

ASJC

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