An effective vaccination approach augments anti-HIV systemic and vaginal immunity in mice with decreased HIV-1 susceptible α4β7high CD4+ T cells

Wei Zhu, Guoping Shi, Haijun Tang, Dorothy E. Lewis, Xiao Tong Song

Research output: Contribution to journalArticle

3 Scopus citations

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 α4β7high 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 α4β7 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.

Original languageEnglish (US)
Pages (from-to)56-66
Number of pages11
JournalCurrent HIV Research
Volume11
Issue number1
DOIs
StatePublished - 2013

Keywords

  • ALDH1A2
  • CCR9
  • Dendritic cell
  • HIV-1 vaccine
  • ShRNA
  • α4β7

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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