MUCOSAL IMMUNIZATION AGAINST GENITAL TRANSMISSION OF SIV

Project: Research project

Project Details

Description

Because HIV is primarily a sexually transmitted disease, any vaccine
intended to halt the dissemination of HIV must prevent transmission
following sexual contact with an infected individual. The rhesus
macaque/SIV animal model has been used to demonstrate vaccine mediated
protection against intravenous challenge with SIV. An animal model of
heterosexual transmission of HIV has been developed in this animal model
system. The objective of this project is to characterize the mucosal
immune response in rhesus macaques immunized mucosally and systemically
with SIV and SIV subunits combined with the mucosal adjuvants and
replicating vectors. If any of the specific strategies produces a strong
genital immune response the animals will be vaginally challenged with
virulent SIV. The challenge will consist of a single vaginal inoculation
with a 100% infectious dose of cell-free SIVmac251. It is important to
emphasize that we are the only group that has defined a 100% vaginal
infectious dose of cell-free SIVmac. The initial experiments will combine mucosal immunization and systemic
boosting with a whole-killed SIV vaccine (in one group of animals) or SIV
gp130 subunit preparation (in another group of animals) and the mucosal
adjuvants CT or CT-B. This experiment is designed to determine if CT or
CTB produces stronger anti-SIV genital immunity and to determine if these
adjuvants improve the local immune response to whole-inactivated virus
and subunits. Both cellular and humoral immune responses to the vaccine
protocols will be assessed in a variety of anatomic sites including: 1)
vaginal mucosa and vaginal secretions, 2) genital lymph nodes, 3)
mesenteric lymph nodes, 4) peripheral lymph nodes and 5) blood. The
immune parameters to be assessed include SIV specific antibody (IgA and
IgG), isotype of SIV specific antibody forming cells (ELISPOT), SIV
neutralizing activity, presence of SIV-specific CTL and antigen specific
T cell proliferation. Samples of cells from all the tissues will be sent
to Drs. McGhee and Kiyono at the University of Alabama at Birmingham to
determine which T helper cell subsets (Th1 or Th2) the immunization
protocols stimulate. If these analyses reveal strong local anti-SIV
immunity, vaginal challenge experiments will be undertaken. In subsequent studies, we will test the ability of a number of mucosal
vectors and adjuvants to elicit SIV-specific genital immunity. Our group
will have live bacterial vectors (Vibrio cholerae and Salmonella
expressing SIVenv and gag), recombinant polio virus and SIV antigen
(gp130) incorporated into aqueous microspheres available for testing in
rhesus macaques. The collaborative immunology group established in this
CMIG will provide an efficient mechanism in which to assess the immune
response to these vaccines. If successful these studies will provide the
basis for vaccine trials designed to prevent the heterosexual
transmission of HIV in humans.
StatusFinished
Effective start/end date11/1/9311/30/00

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $218,108.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

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

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