MATERNO-FETAL HIV TRANSMISSION - MODEL FOR VACCINES

  • Rubinstein, Arye (PI)
  • Baum, Stephen (PI)
  • Horwitz, Marshall (PI)
  • Friedland, Gerald (PI)
  • Rubenstein, Arye (PI)

Project: Research project

Project Details

Description

This program grant is based on our preliminary studies limiting high
affinity antibodies reactive with the HIV-1 MN strains gp120 Primary
Neutralizing Domain (gp120 MN PND) to reduced materno-fetal HIV
transmission. This application includes two interrelated HIV
transmission projects supported by two core facilities. The first
project will assess high affinity antibodies to the gp120 MN PND in
materno-fetal pairs infected by the HIV-1 MN strain. The phenotype and
function of these antibodies will be evaluated in HIV infected pregnant
women and their neonates. Fetal outcme (e.g. HIV infection status) will
be correlated with levels of high affinity MN-PND antibodies, with their
in vitro biological function (e.g. neutralization of HIV-1-MN) and with
maternal virus load. Based on preliminary data previously obtained here
showing a significant correlation between the lack of materno-fetal HIV
transmission and the presence of these MN-PND antibodies, we propose in
the second project to develop a materno-fetal HIV transmission blocking
vaccine. For that purpose MN-PND peptides will be conjugated to tetanus
toxoid or to PPD for immunization of HIV seropositive women who have a
high robability of becoming pregnant within one year. The two
supporting core facilities consist of (a) an vaccine production facility
and an animal testing facility, and (b) a virus production, purification
and neutralization core, in which HIV or its components will be obtained
from patients and assays will be conducted to measure the biological
function (e.g. HIV-1-MN neutralization, ADCC) of purified MN-PND
antibodies and to assess the outcome of the MN-PND vaccine. If
successful, this transmission blocking vaccine trial will later be
expanded to sero-negative healthy individuals, alone or in conjunction
with other vaccines such as the HIV-1 gag vaccine.
StatusFinished
Effective start/end date5/1/831/31/94

ASJC

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