DEVELOPMENT OF VACCINIA-BASED VACCINES FOR HIV AND SIV

  • Desrosiers, Ronald Charles (PI)
  • Roberts, Bryan (PI)
  • Panicali, Dennis (PI)
  • Panicali, Dennis (PI)
  • Johnson, Philip (PI)
  • Mazzara, Gail (PI)
  • Sullivan, John (PI)
  • Mazzara, Gail (PI)
  • Johnson, Philip (PI)
  • Sullivan, John (PI)
  • Letvin, Norman (PI)

Project: Research project

Description

The emergence of the Acquired Immunodeficiency Disease (AIDS)
pandemic may represent the most serious global public health threat
of the 20th century. The goal of the proposed research is the
development of an efficacious vaccine against multiple strains of
the Human Immunodeficiency Virus (HIV), the etiological agent of
AIDS. This proposal describes the design, construction and
evaluation of a series of vaccinia-based recombinant vaccines for
both HIV-1 and the related Simian Immunodeficiency Virus (SIV).
This will be accomplished through a coordinated program combining
the talents of both academic and industrial scientists. These
vaccines will express multiple HIV-1 or SIV antigens in
conformations that elicit appropriate humoral and cell-mediated
immune responses. Novel methods developed at AbT for rapidly
generating and selecting vaccinia recombinants expressing multiple
antigens are described. The nature and magnitude of the humoral
and cell mediated immune responses elicited by the recombinant
viruses will be evaluated in both murine and non-human primate
systems. In addition, histocompatible human target cells infected
with the recombinant viruses will be used to assess, in vitro,
cytotoxic cellular responses of HIV-1 infected individuals to the
vaccinia-expressed HIV-1 antigens. These in vitro studies will
help define the HIV-1/SIV antigens and /or antigenic epitopes most
appropriate for inclusion into a potential vaccine. The
demonstration of the efficacy of an HIV-1 vaccine is hampered by
the lack of the induction of an acquired immunodeficiency syndrome
in HIV-1 infected non-human primates. The development of an AIDS-
like syndrome in macaques following infection with SIV allows the
evaluation of the efficacy of potential vaccines in a primate
model. This system will permit characterization of the immune
responses induced and the protection afforded by vaccinia
recombinants expressing combinations of SIV antigens. The
information derived from these combined HIV-1 and SIV studies will
be elaborated to produce safe and efficacious vaccinia-based HIV-
1 vaccines for use in humans.
StatusFinished
Effective start/end date3/1/8910/31/05

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

Vaccinia
Simian Immunodeficiency Virus
Macaca
Vaccines
Synthetic Vaccines
HIV-1
Primates
AIDS Vaccines
Research
New England
Vaccinia virus
Immunosuppressive Agents
Biotechnology
HIV Infections
Immunity
Viruses
Safety
Antigens

ASJC

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