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
Current HIV Research
Title:An Effective Vaccination Approach Augments Anti-HIV Systemic and Vaginal Immunity in Mice with Decreased HIV-1 Susceptible α4β7high CD4+ T Cells
Volume: 11 Issue: 1
Author(s): Wei Zhu, Guoping Shi, Haijun Tang, Dorothy E. Lewis and Xiao-Tong Song
Affiliation:
Keywords: ALDH1a2, α4β7, CCR9, CD4+ T cell, dendritic cell, HIV-1 Vaccine, shRNA, DCs, Susceptible, vaginal
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.
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Cite this article as:
Zhu Wei, Shi Guoping, Tang Haijun, E. Lewis Dorothy and Song Xiao-Tong, An Effective Vaccination Approach Augments Anti-HIV Systemic and Vaginal Immunity in Mice with Decreased HIV-1 Susceptible α4β7high CD4+ T Cells, Current HIV Research 2013; 11 (1) . https://dx.doi.org/10.2174/1570162X11311010008
DOI https://dx.doi.org/10.2174/1570162X11311010008 |
Print ISSN 1570-162X |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4251 |
Call for Papers in Thematic Issues
HIV vaccine development
The development of a safe and effective vaccine that impedes HIV-1 transmission and/or limits the severity of infection remains a public health priority. The HIV-1/AIDS pandemic continues to have a disproportionate impact on vulnerable and under-served communities in the USA and globally. In the USA, minority communities that have relatively ...read more
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