CCL19 and CCL28 Assist Herpes Simplex Virus 2 Glycoprotein D To Induce Protective Systemic Immunity against Genital Viral Challenge.
CCL19 and CCL28 Assist Herpes Simplex Virus 2 Glycoprotein D To Induce Protective Systemic Immunity against Genital Viral Challenge.
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CCL19 和 CCL28 协助单纯疱疹病毒 2 糖蛋白 D 诱导针对生殖器病毒攻击的保护性系统免疫。
DOI：
10.1128/msphere.00058-21
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发表时间：
2021-04-28
期刊：
影响因子：
4.8
通讯作者：
Hu Q
中科院分区：
文献类型：
--
作者：
Yan Y;Hu K;Fu M;Deng X;Luo S;Tong L;Guan X;He S;Li C;Jin W;Du T;Zheng Z;Zhang M;Liu Y;Hu Q
有效的HSV-2疫苗应诱导针对病毒粘膜感染的抗原（Ag）特异性免疫应答。本研究揭示趋化因子CCL 19或CCL 28增强HSV-2糖蛋白D胞外域（gD-306 aa）诱导的针对阴道病毒攻击的免疫应答。有效的全身免疫对于召回的粘膜免疫应答是重要的，但在防御粘膜病毒感染时，它通常在粘膜部位保持较低水平。基于我们先前的发现，即增强的免疫应答可以通过免疫原与分子佐剂的组合来实现，在此我们设计了趋化因子-抗原（Ag）融合构建体（CCL 19-或CCL 28-单纯疱疹病毒2型糖蛋白D [HSV-2 gD]）。肌内（i.m.）以不同的DNA疫苗在初免和加强策略中进行免疫，BALB/c小鼠通过生殖道用致死剂量的HSV-2攻击。分析Ag特异性免疫应答和趋化因子受体特异性淋巴细胞，以确定CCL 19和CCL 28在增强体液和细胞免疫中的作用。CCL 19和CCL 28均有效诱导持久的HSV-2 gD特异性全身免疫。与CCL 19相比，需要较少的CCL 28来引发HSV-2 gD特异性血清伊加应答、免疫球蛋白（IG）亚类和细胞因子的Th 1-和Th 2-样应答以及脾脏中的CCR 3 + T细胞富集（>8.5倍）。这些发现共同证明了CCL 28倾向于协助免疫原诱导比CCL 19更有效的保护性免疫。这项工作提供了一个有前途的疫苗接种策略对HSV-2和其他性传播病毒引起的粘膜感染的应用潜力的信息。重要性有效的HSV-2疫苗应诱导针对病毒粘膜感染的抗原（Ag）特异性免疫应答。本研究揭示趋化因子CCL 19或CCL 28增强HSV-2糖蛋白D胞外域（gD-306 aa）诱导的针对阴道病毒攻击的免疫应答。除了引发强烈的体液免疫应答外，趋化因子-Ag融合构建体还诱导Th 1-和Th 2-样免疫应答，其特征在于分泌多个IG亚类和细胞因子，其能够在HSV-2攻击后被召回，而CCL 28似乎比CCL 19更有效地促进gD-引发的免疫应答以及T细胞向次级淋巴组织的迁移。重要的是，CCL 19和CCL 28均显著促进gD在生殖道中诱导保护性粘膜免疫应答。上述发现共同强调了CCL 19或CCL 28与gD组合作为控制HSV-2感染的疫苗接种策略的潜力。
An effective HSV-2 vaccine should induce antigen (Ag)-specific immune responses against viral mucosal infection. This study reveals that chemokine CCL19 or CCL28 enhanced HSV-2 glycoprotein D ectodomain (gD-306aa)-induced immune responses against vaginal virus challenge. Potent systemic immunity is important for recalled mucosal immune responses, but in the defense against mucosal viral infections, it usually remains low at mucosal sites. Based on our previous findings that enhanced immune responses can be achieved by immunization with an immunogen in combination with a molecular adjuvant, here we designed chemokine-antigen (Ag) fusion constructs (CCL19- or CCL28-herpes simplex virus 2 glycoprotein D [HSV-2 gD]). After intramuscular (i.m.) immunization with different DNA vaccines in a prime and boost strategy, BALB/c mice were challenged with a lethal dose of HSV-2 through the genital tract. Ag-specific immune responses and chemokine receptor-specific lymphocytes were analyzed to determine the effects of CCL19 and CCL28 in strengthening humoral and cellular immunity. Both CCL19 and CCL28 were efficient in inducing long-lasting HSV-2 gD-specific systemic immunity. Compared to CCL19, less CCL28 was required to elicit HSV-2 gD-specific serum IgA responses, Th1- and Th2-like responses of immunoglobulin (Ig) subclasses and cytokines, and CCR3+ T cell enrichment (>8.5-fold) in spleens. These findings together demonstrate that CCL28 tends to assist an immunogen to induce more potently protective immunity than CCL19. This work provides information for the application potential of a promising vaccination strategy against mucosal infections caused by HSV-2 and other sexually transmitted viruses. IMPORTANCE An effective HSV-2 vaccine should induce antigen (Ag)-specific immune responses against viral mucosal infection. This study reveals that chemokine CCL19 or CCL28 enhanced HSV-2 glycoprotein D ectodomain (gD-306aa)-induced immune responses against vaginal virus challenge. In addition to eliciting robust humoral immune responses, the chemokine-Ag fusion construct also induced Th1- and Th2-like immune responses characterized by the secretion of multiple Ig subclasses and cytokines that were able to be recalled after HSV-2 challenge, while CCL28 appeared to be more effective than CCL19 in promoting gD-elicited immune responses as well as the migration of T cells to secondary lymph tissues. Of importance, both CCL19 and CCL28 significantly facilitated gD to induce protective mucosal immune responses in the genital tract. The above-described findings together highlight the potential of CCL19 or CCL28 in combination with gD as a vaccination strategy to control HSV-2 infection.
影响因子：
3.7
作者：
Isik G;van Montfort T;Boot M;Cobos Jiménez V;Kootstra NA;Sanders RW
通讯作者：
Sanders RW