Induction of HIV-1-Specific Mucosal Immune Responses Following Intramuscular Recombinant Adenovirus Serotype 26 HIV-1 Vaccination of Humans
Induction of HIV-1-Specific Mucosal Immune Responses Following Intramuscular Recombinant Adenovirus Serotype 26 HIV-1 Vaccination of Humans
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DOI：
10.1093/infdis/jiu485
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发表时间：
2015-02-15
影响因子：
6.4
通讯作者：
Barouch, Dan H.
中科院分区：
文献类型：
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作者：
Baden, Lindsey R.;Liu, Jinyan;Barouch, Dan H.
背景资料。确定对候选人类免疫缺陷病毒1型(HIV-1)疫苗的粘膜免疫反应和炎症是当前HIV-1疫苗领域的研究重点。特别是，肌肉免疫是否能在人体粘膜表面引起免疫反应尚不清楚。在这项双盲、随机、安慰剂对照的临床试验中，我们在基线AD26血清阴性和AD26血清阳性的健康志愿者中评估了候选腺病毒26型(AD26)载体HIV-1包膜(Env)疫苗的系统和粘膜免疫应答。用直肠Weck-Cel海绵和直肠活检进行系统的粘膜采样。肌内免疫可在大多数受试者中诱发全身和粘膜环境特异性体液和细胞免疫反应。先前存在AD26特异性中和抗体的个体的疫苗诱导的免疫反应与AD26血清阴性的受试者相当。通过组织病理学或流式细胞术，我们也观察到接种疫苗后激活的总的或载体特异性的粘膜CD4(+)T淋巴细胞没有增加。这些数据表明，单次肌肉注射这种AD26载体的HIV-1Env疫苗可以在人类中引发系统和粘膜免疫反应。诱导抗原特异性体液和细胞黏膜免疫并不伴随黏膜炎症的明显增加。
Background. Defining mucosal immune responses and inflammation to candidate human immunodeficiency virus type 1 (HIV-1) vaccines represents a current research priority for the HIV-1 vaccine field. In particular, it is unclear whether intramuscular immunization can elicit immune responses at mucosal surfaces in humans.Methods. In this double-blind, randomized, placebo-controlled clinical trial, we evaluated systemic and mucosal immune responses to a candidate adenovirus serotype 26 (Ad26) vectored HIV-1 envelop (Env) vaccine in baseline Ad26-seronegative and Ad26-seropositive healthy volunteers. Systematic mucosal sampling with rectal Weck-Cel sponges and rectal biopsies were performed.Results. Intramuscular immunization elicited both systemic and mucosal Env-specific humoral and cellular immune responses in the majority of subjects. Individuals with preexisting Ad26-specific neutralizing antibodies had vaccine-elicited immune responses comparable to those of subjects who were Ad26 seronegative. We also observed no increase in activated total or vector-specific mucosal CD4(+) T lymphocytes following vaccination by either histopathology or flow cytometry.Conclusions. These data demonstrate that a single intramuscular administration of this Ad26-vectored HIV-1 Env vaccine elicited both systemic and mucosal immune responses in humans. Induction of antigen-specific humoral and cellular mucosal immunity was not accompanied by a detectable increase in mucosal inflammation.