Virus-like particles (VLP) containing SIV gagp27 have been extensively studied for their ability to induce p27-specific immune responses after mucosal immunization in female and male macaques.30318081 Vaginal or rectal immunization with SIV p27-VLP followed by oral immunization with SIV p27- gagVLP was found to be an effective immunization protocol for the induction of anti-p27 IgA responses in vaginal and rectal secretions, respectively.3080 The combined vaginal-oral immunizations with SIV p27- gag VLP also induced p27-specific lymphocyte-proliferative responses in cells isolated from the blood, spleen, genital lymph nodes, and iliac lymph nodes, but not the mesenteric, bronchial, or axillary lymph nodes.30 The combination of oral and rectal immunization followed by an intramuscular boost with SIV p27-gag VLP induced p27-specific lymphocyte-proliferative responses in the blood, spleen, internal iliac, inferior mesenteric, and iliac-paraaortic lymph nodes, but not in the superior mesenteric, bronchial, or axillary lymph nodes.30 Topical urethral immunization of male macaques followed by oral immunization with SIV p27- gag VLP also induced p27-specific lymphocytes in the blood, spleen, internal iliac, inferior mesenteric, and iliac paraaortic lymph node.31 In contrast, intramuscular immunization of female or male macaques induced p27-specific lymphocyte proliferative responses in the spleen and blood only.3031 Therefore, mucosal immunization was required for the induction of SIV-specific lymphocytes that reside in lymph nodes that drain mucosal tissues near the genitourinary tract. The observation that mucosal immunization induced compartmentalized mu-cosal and systemic immune responses led these investigators to hypothesize that the induction of mucosal and systemic immune responses may prevent mucosally transmitted HIV infection at three different states by (1) preventing HIV infection at the mucosal surface, (2) preventing the spread of HIV
to regional lymph nodes, and/or (3) blocking the dissemination of HIV to circulating immune cells (Fig. 2).15-30-31
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