Mucosal immunization with HIV-1 peptide vaccine induces mucosal and systemic cytotoxic T lymphocytes and protective immunity in mice against intrarectal recombinant HIV-vaccinia challenge
Mucosal immunization with HIV-1 peptide vaccine induces mucosal and systemic cytotoxic T lymphocytes and protective immunity in mice against intrarectal recombinant HIV-vaccinia challenge
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DOI：
10.1073/pnas.95.4.1709
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发表时间：
1998-02-17
影响因子：
11.1
通讯作者：
Berzofsky, JA
中科院分区：
文献类型：
--
作者：
Belyakov, IM;Derby, MA;Berzofsky, JA
粘膜组织是HIV进入和初始感染的主要部位，因此，粘膜细胞毒性T淋巴细胞（CTL）应答的诱导是有效的HIV疫苗的重要特征。然而，关于在粘膜中诱导这种保护性CTL应答的方法知之甚少。多决定簇HIV肽加霍乱毒素佐剂诱导持久的抗原特异性CTL记忆，（派伊尔集合淋巴结）和效应器（固有层）粘膜部位以及全身部位（脾），而全身免疫仅在脾中诱导特异性CTL，霍乱毒素佐剂，CTL识别用HIV肽脉冲或表达M-r 160，000（gp 160）的内源性全包膜糖蛋白的靶细胞。探索CTL诱导的要求，我们通过使用抗体处理的和敲除小鼠显示粘膜CTL应答是白细胞介素12和干扰素-γ依赖的。最后，为了确定粘膜应答是否实际上对病毒的局部粘膜攻击具有保护作用，我们表明用合成HIV肽疫苗的直肠内免疫保护小鼠免受表达HIV-1 IIIB gp 160的重组牛痘病毒的粘膜攻击的感染，这些研究提供了开发HIV疫苗的方法，该疫苗在粘膜和全身免疫系统中诱导CTL免疫，并保护抗表达HIV-1 gp 160的病毒的粘膜感染。
Mucosal tissues are major sites of HIV entry and initial infection, Thus, the induction of a mucosal cytotoxic T lymphocyte (CTL) response is an important feature fbr an effective HIV vaccine, However, little is known about approaches to induce such a protective CTL response in the mucosa, Here for the first time we show that intrarectal immunization with a synthetic, multideterminant HIV peptide plus cholera toxin adjuvant induced long-lasting, antigen-specific CTL memory in both the inductive (Peyer's patch) and effector (lamina propria) mucosal sites, as well as in systemic sites (spleen), whereas systemic immunization induced specific CTL only in the spleen, Cholera toxin adjuvant, while enhancing the response, was not essential, The CTL recognized target cells either pulsed with HIV peptide or expressing endogenous whole envelope glycoprotein of M-r 160,000 (gp160), Exploring the requirements for CTL induction, we show that mucosal CTL responses are both interleukin 12 and interferon-gamma dependent by using antibody-treated and knockout mice, Finally, to determine whether a mucosal response is actually protective against local mucosal challenge with virus, we show that intrarectal immunization with the synthetic HIV peptide vaccine protected mice against infection via mucosal challenge with a recombinant vaccinia virus expressing HIV-1IIIB gp160, These studies provide an approach to development of an HIV vaccine that induces CTL immunity in the mucosal and systemic immune systems and protects against mucosal infection with a virus expressing HIV-1 gp160.