Genital Tract Mucosal Immunity In Rwanda Women (Exposed Seronegative)

Rwandan PI: Elisaphane Munyazesa, MSc; Co-investigators:

  • Betsy Herold, MD
  • Eugene Mutimura PhD
  • Kathryn Anastos, MD
  • Marla Keller, MD
  • Mardge Cohen MD
  • Audrey French MD
  • Jean Claude Dusingize, MD
  • Jean d'Amour Sinayobye, MD
  • Linda Baum, PhD
  • Richard Novak MD
  • Background

    We refer to these women as highly exposed seronegative (ESN) women. It would be extremely valuable to know the particular components of the genital immune response that protects these women against heterosexual transmission of HIV. This knowledge could be used to develop a vaccine that could effectively and selectively stimulate protective local immunity in the female genital tract against HIV infection.

    Specific Aim

    To compare the humoral immune response in the genital tract of ESN women. Rationale: If genital tract antibodies from ESN women with similar risk behaviors in diverse geographic regions target similar broadly neutralizing epitopes, these epitopes could serve as the basis for vaccine(s) with much wider application than currently designed clade specific vaccines. We predict that the HIV specific antibody response in ESN women from Rwanda will be similar to the US cohort of ESN we are recruiting in parallel.

    We expect that mucosal antibodies from ESN women will bind to the broadly neutralizing epitopes with similar frequency as the ESN women from other country cohort, and will also display cross clade activity with similar frequency. This would provide strong support for the hypothesis that these epitope sequences have protective potential, since they would be preserved in diverse parts of the world and across clades. The CSW mucosal samples may have antibody epitopes that differ from the discordant women, as has been seen elsewhere. Alternatively, the Env epitopes will be unique, and unrelated to those seen in the ESN women from the US, which would not eliminate the possibility that they confer some protection from infection, but would not support this hypothesis.

    Recruitment Plan

    This cohort will in part be recruited in part from the existing Rwanda women inter association study assessment cohort which began with 715 HIV seropositive women and 221 seronegative women

    Existing Seronegative RWISA participants

    Of the seronegative women, ~30 reported current commercial sex work (CSW) at a RWISA visit. Additionally, 9 -15 women have reported an HIV-positive partner at one of the RWISA visit. We are requesting use of existing banked plasma and cervicovaginal lavage fluid from these women from visits where they reported the high-risk behavior. In addition, for women who continue high-risk behavior, we will approach them for consent to participate in enhanced sampling during their RWISA visits, as per the protocol described in the appendix.

    Existing Seropositive RWISA participants

    We will request existing specimens for 20 seropositive RWISA participants. In addition, we will approach 48 HIV-infected RWISA participants over the 5 years of the study for enhanced sampling. New Recruitment: Potential participants will be approached at their RWISA visits, through male HIV-infected clients or when receiving gynecologic service at the Nyacyonga health center in Kigali. They will be screened to see if they meet the inclusion criteria below.