Mucosal HIV Vaccine Targeting Host Epithelial Stem Cells for Long-Term Immunity

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Presentation Time: 08:00 AM - 08:15 AM
Abstract ID: 6083 - B

Presenting Author:
Marie-Claire Gauduin , Professor at Texas Biomed. Res. Inst.

Abstract:

An HIV vaccine developed under the control of Involucrin promoter, was tested for its ability to drive antigenic expressions in terminally-differentiated epithelial cells, induce mucosal responses and protection. Twelve female macaques were immunized (once), monitored for specific responses in blood, mucosal secretions, various tissues. Eight females were challenged (wks 12 or 24) with repeated SIV. Eight additional females served as unvaccinated infected controls.  Two wks post-vaccine, strong mucosal IgG/IgA responses and specific T-cells were detected. Immunohistofluorescence revealed antigens-expression in epithelia upper-layers. SIVenv was detected via anti-gp120 immunoPET/CT in vagina, draining-LN. Challenges demonstrated significant delays and lower viremia (2-3 logs-reduction-peak; 4-5 logs-reduction set-point) to undetectable 10-20 wks post-SIV. Robust specific T-cell responses were detected in blood, LN, various tissues. Controls had high viremia (7-8 logs viral-RNA copies/ml) and significant gut CD4 cells depletion. We showed positive correlations between T-cell and viremia, inverse associations between mucosa IgG/IgA and viremia. Vaccinees had durable aviremic control for 3 yrs when CD8 were depleted. Dramatic fall in viremia coincided with CD8 cells recovery. The epithelial stem cell-based vaccine served as antigen-delivery, generated specific mucosal responses, led to significant delays in infection, rapid viremia decrease, to durable undetectable SIV control.