中科院武漢病毒研究所胡勤學(xué)學(xué)科組在HIV免疫應(yīng)答研究中取得新進(jìn)展，相關(guān)結(jié)果作為封面論文于2013年8月發(fā)表在免疫學(xué)領(lǐng)域期刊The Journal of Immunology上,。
HIV疫苗的研究經(jīng)歷近三十年,，但目前仍沒有有效的HIV疫苗問世,。HIV包膜糖蛋白（Env）是預(yù)防性疫苗的首選靶標(biāo),，然而,，多種形式的Env均不能誘導(dǎo)機(jī)體產(chǎn)生高水平的廣譜中和能力,。增強(qiáng)抗原免疫原性的手段之一是選用合適的佐劑,。胡勤學(xué)學(xué)科組研究了三個(gè)質(zhì)粒型細(xì)胞因子：pAPRIL,、pCCL19和pCCL28，作為分子佐劑對(duì)HIV疫苗候選抗原gp140的免疫增強(qiáng)作用及其潛在分子機(jī)制,。
研究結(jié)果表明,，pCCL19和pCCL28均能夠顯著增強(qiáng)系統(tǒng)性以及黏膜部位的抗原特異性的抗體水平，而pAPRIL則未表現(xiàn)出明顯的免疫增強(qiáng)作用,。此外,，血清和黏膜部位增強(qiáng)的抗體水平具有更好的中和同源以及異源HIV的能力，其中和能力分別與血清中抗原特異性的IgG以及黏膜部位抗原特異性IgA水平正相關(guān),。進(jìn)一步的實(shí)驗(yàn)表明,，pCCL19和pCCL28能夠平衡地增強(qiáng)Th1/Th2細(xì)胞免疫應(yīng)答水平以及增加免疫小鼠直腸黏膜表面的IgA+細(xì)胞數(shù)目。pCCL19能夠招募CCR7+DC細(xì)胞遷移至腸系膜淋巴結(jié)以及招募CCR7+DC細(xì)胞和CCR7+T細(xì)胞遷移至脾臟,；而pCCL28則能夠招募CCR10+B細(xì)胞遷移至脾臟和腸系膜淋巴結(jié),。以上結(jié)果表明，pCCL19和pCCL28能夠增強(qiáng)HIVEnv特異性的系統(tǒng)性以及黏膜部位的抗體應(yīng)答水平和T細(xì)胞免疫應(yīng)答水平,，這種增強(qiáng)效果可能與它們能夠招募特定免疫細(xì)胞遷移至二級(jí)淋巴器官和黏膜組織相關(guān),。
以上發(fā)現(xiàn)對(duì)定向誘導(dǎo)針對(duì)HIV抗原的免疫應(yīng)答特別是黏膜免疫應(yīng)答具有指導(dǎo)意義。該項(xiàng)研究受到科技部和國(guó)家自然科學(xué)基金委等的支持,。（生物谷 Bioon.com）
生物谷推薦的英文摘要
J. Immunol. doi: 10.4049/?jimmunol.1300120
CCL19 and CCL28 Augment Mucosal and Systemic Immune Responses to HIV-1 gp140 by Mobilizing Responsive Immunocytes into Secondary Lymph Nodes and Mucosal Tissue
Kai Hu*,†, Sukun Luo*,†, Lina Tong*, Xin Huang*,†, Wei Jin*,†, Wenjie Huang*, Tao Du*,†, Yan Yan*,†, Siyi He*,†, George E. Griffin‡, Robin J. Shattock§ and Qinxue Hu*,‡
Induction of broad and potent neutralizing Abs at the mucosal portals of entry remains a primary goal for most vaccines against mucosally acquired viral infections. Selection of appropriate adjuvants capable of promoting both systemic and mucosal responses will be crucial for the development of effective immunization strategies. In this study, we investigated whether plasmid codelivery of cytokines APRIL, CCL19, or CCL28 can enhance Ag-induced immune responses to HIV-1 gp140. Our results demonstrated that pCCL19 and pCCL28, but not pAPRIL, significantly enhanced Ag-specific systemic and mucosal Ab responses. gp140-specific Abs in serum enhanced by pCCL19 or pCCL28 were broadly distributed across all four IgG subclasses, of which IgG1 was predominant. The enhanced systemic and mucosal Abs showed increased neutralizing activity against both homologous and heterologous HIV-1, and potency correlated with gp140-specific serum IgG and vaginal IgA levels. Measurement of gp140-specific cytokines produced by splenocytes demonstrated that pCCL19 and pCCL28 augmented balanced Th1/Th2 responses. pCCL19 and pCCL28 also increased IgA+ cells in colorectal mucosal tissue. pCCL19 codelivery resulted in an increase of CCR7+ CD11c+ cells in mesenteric lymph nodes and both CCR7+ CD11c+ cells and CCR7+ CD3e+ cells in spleen, whereas pCCL28 codelivery resulted in an augment of CCR10+ CD19+ cells in both spleen and mesenteric lymph nodes. Together, our data indicate that pCCL19 and pCCL28 can enhance HIV-1 envelope–specific systemic and mucosal Ab responses, as well as T cell responses. Such enhancements appear to be associated with mobilization of responsive immunocytes into secondary lymphoid organs and mucosal tissues through interactions with corresponding receptors.
