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Current HIV Research

Editor-in-Chief

ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

An Effective Vaccination Approach Augments Anti-HIV Systemic and Vaginal Immunity in Mice with Decreased HIV-1 Susceptible α4β7high CD4+ T Cells

Author(s): Wei Zhu, Guoping Shi, Haijun Tang, Dorothy E. Lewis and Xiao-Tong Song

Volume 11 , Issue 1 , 2013

Page: [56 - 66] Pages: 11

DOI: 10.2174/1570162X11311010008

Price: $65

Abstract

HIV-1 preferentially infects activated CD4+ T cells expressing α4β7 integrin and conventional vaccination approaches non-selectively induce immune responses including α4β7high CD4+ T cells, suggesting that current candidate AIDS vaccines may produce more target cells for HIV-1 and paradoxically enhance HIV-1 infection. Thus it remains a challenge to selectively induce robust anti-HIV immunity without the unwanted HIV-1 susceptible α4β77high CD4+ T cells. Here we describe a vaccination strategy that targets ALDH1a2, a retinoic acid producing enzyme in dendritic cells (DCs). Silencing ALDH1a2 in DCs enhanced the maturation and production of proinflammatory cytokines of DCs and promoted Th1/Th2 differentiation while suppressing Treg. ALDH1a2-silenced DCs effectively downregulated the expression of guthoming receptors α4β77 and CCR9 on activated T and B lymphocytes. Consequently, intranasal immunization of a lentiviral vaccine encoding ALDH1a2 shRNA and HIV-1 gp140 redirected gp140-specific mucosal T cell and antibody responses from the gut to the vaginal tract, while dramatically enhancing systemic gp140-specific immune responses. We further demonstrated that silencing ALDH1a2 in human DCs resulted in downregulation of β7 expression on activated autologous CD4+ T cells. Hence this study provides a unique and effective strategy to induce α4β7low anti-HIV immune responses.

Keywords: ALDH1a2, α4β7, CCR9, CD4+ T cell, dendritic cell, HIV-1 Vaccine, shRNA, DCs, Susceptible, vaginal


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