Influence of mucosal and parenteral immunization with a replication-defective mutant of HSV-2 on immune responses and protection from genital challenge
Influence of mucosal and parenteral immunization with a replication-defective mutant of HSV-2 on immune responses and protection from genital challenge
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DOI：
10.1006/viro.1998.9047
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发表时间：
1998-03-30
期刊：
影响因子：
3.7
通讯作者：
Knipe, DM
中科院分区：
文献类型：
--
作者：
Morrison, LA;Da Costa, XJ;Knipe, DM
单纯疱疹病毒（HSV）最常在粘膜表面引发感染;因此粘膜免疫应答可能在防御HSV感染中很重要。我们已经研究了在用HSV-2的复制缺陷型突变体免疫的小鼠中，引发粘膜和全身免疫应答对保护生殖器免受强毒HSV-2攻击感染的影响。此外，我们还研究了在已知可提供保护的条件下，通过不同途径免疫接种引起的免疫应答类型。我们观察到，在肠胃外和远端粘膜部位的免疫接种产生的免疫应答在保护免受强毒HSV-2攻击感染方面具有累加效应。单独在这些部位进行免疫可预防攻击病毒感染后的麻痹和死亡，并减少生殖器粘膜中攻击病毒的复制，尽管皮下免疫在减少病毒复制方面更有效。在两个位点同时免疫导致攻击病毒的粘膜复制的最大减少。产生的反应类型也受到免疫途径的影响。皮下免疫导致强烈的系统性免疫应答，其在某种程度上偏向于Th 1 T细胞应答，而鼻内免疫诱导粘膜以及系统性免疫，如阴道分泌物中的HSV特异性伊加所证明的，以及更强的偏向于Th 1应答。这些结果表明，粘膜免疫可以补充保护性免疫对HSV-2生殖器感染产生的胃肠外免疫与复制缺陷型突变病毒。(C)北京：科学出版社.
Herpes simplex virus (HSV) most frequently initiates infection at a mucosal surface; thus mucosal immune responses are likely to be important in defense against HSV infection. We have examined the effects of eliciting mucosal as well as systemic immune responses on protection against genital challenge infection with virulent HSV-2 in mice immunized with a replication-defective mutant of HSV-2. In addition, we have examined the types of immune responses elicited by immunization by the different routes under conditions known to provide protection. We observed that immunizations at parenteral and distal mucosal sites generate immune responses that have an additive effect in protection against challenge infection with virulent HSV-2. Immunization at either of these sites alone prevented paralysis and death after challenge virus infection and reduced replication of the challenge virus in the genital mucosa, although subcutaneous immunization was more effective in reducing virus replication. Simultaneous immunization at the two sites led to the greatest reduction in mucosal replication of challenge virus. The type of response generated was also affected by the route of immunization. Subcutaneous immunization results in a strong systemic immune response that is somewhat biased toward a Th1 T cell response, while intranasal immunization induces mucosal as well as systemic immunity, as evidenced by HSV-specific IgA in Vaginal secretions, and a stronger bias toward a Th1 response. These results suggest that mucosal immunization may complement protective immunity against HSV-2 genital infection generated by parenteral immunization with replication-defective mutant virus. (C) 1998 Academic Press.