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Inhibition of Retinoic Acid Production for HIV Vaccination

技術優勢

- A vaccine strategy that circumvents the problem of induction of HIV-1 virus infection targets by current HIV vaccine candidates.- In vivo blockade of ALDH1a2 not only augments anti-HIV vaginal mucosal immunity, the most critical defense layer, but also enhances anti-HIV systemic immune responses.- Silencing ALDH1a2 in human DCs inhibits the expression of ß7 on activated CD4+ T cells, demonstrating strong clinical relevance.

詳細技術說明

Publications:An effective vaccination approach augments anti-HIV systemic and vaginal immunity in mice with decreased HIV-1 susceptible a4ß7high CD4+ T cells. Zhu W, Shi G, Tang H, Lewis DE, Song XT. Curr HIV Res. 2013 Jan;11(1):56-66.

*Abstract

Most new human HIV-1 infections worldwide occur via the mucosal route, thus an effective HIV-1 vaccine must elicit antiviral immune responses in the mucosa. HIV-1 preferentially infects activated CD4(+) T cells expressing a4ß7 integrin, and conventional vaccination approaches non-selectively enhance the a4ß7(high) CD4(+) T cell population. This suggests that current candidate AIDS vaccines may produce more target cells for HIV-1 and paradoxically enhance HIV-1 infection.Dendritic cells (DCs) produce retinoic acid (RA) that induces and enhances the expression of a4ß7 on activated T and B cells and imprints them for gut-homing. Based on this fact, the inventors have developed a vaccination strategy that targets ALDH1a2, a retinoic acid producing enzyme in DCs, as a novel way to induce more effective anti-HIV immune responses.Silencing ALDH1a2 in DCs potently downregulated the expression of a4ß7 on activated T and B lymphocytes. As a result, immunization of ALDH1a2-silenced lentiviral vaccine greatly enhances anti-HIV gp140 immune responses in the vaginal tract and periphery, but not intestine, providing a unique strategy to redistribute anti-HIV mucosal immune responses on the front line of defense against HIV-1 with concomitant suppression of a4ß7high CD4+ T cells.

國家/地區

美國