最近,耶鲁大学研究者们对小鼠模型实施的一项研究获得了有益的结果,即一个新的疫苗或许可以用于保护机体免受生殖器疱疹以及其它性传播疾病(例如艾滋病)的侵扰。相关结果发表在Nature杂志上。

-2012年11月15日《自然》

中文翻译


【题目】通过建立局部记忆性T细胞防止生殖器疱疹的疫苗策略

【译文】大多数成功的现存疫苗主要是依赖中和抗体,这可能不需要B细胞的特异性解剖学定位。然而,依赖T细胞的有效疫苗很难开发,主要是因为强大的全身记忆性T细胞反应不一定与宿主保护相联系。在外周位点中,与循环记忆性T细胞相比,组织中记忆性T细胞提供了更有力的保护作用。本研究描述了一种简单的非炎性疫苗策略,据此可以在外周组织中建立一种保护性记忆T细胞群。女性生殖道是性传播感染的侵入途径,是当没有炎症或感染时可以阻止活化的T细胞进入的免疫限制组织。为了克服这一障碍,我们开发了一种称之为‘prime和pull’的疫苗策略,以在潜在病毒暴露位点处建立局部组织存在的记忆性T细胞。该方法分为两步:常规胃肠道外疫苗接种以诱导系统T细胞反应(prime),随后通过利用限制性生殖道局部细胞因子的途径招募活化的T细胞(pull),限制性生殖道中这类T细胞建立了长期生境和介导保护性免疫。 小鼠中,prime和pull的操作减少了感染性单纯疱疹病毒2在感觉神经元中的传播,并阻止临床疾病的发展。 这些结果揭示了一种抵抗单纯疱疹病毒2的潜在疫苗策略,这种策略还可以潜在抵御其他性传播感染,如人免疫缺陷病毒。

英文原稿


[Title]: A vaccine strategy that protects against genital herpes by establishing local memory T cells

[Authors]:Haina Shin1 & Akiko Iwasaki1

[Abstract]Most successful existing vaccines rely on neutralizing antibodies, which may not require specific anatomical localization of B cells. However, efficacious vaccines that rely on T cells for protection have been difficult to develop, as robust systemic memory T-cell responses do not necessarily correlate with host protection. In peripheral sites, tissue-resident memory T cells provide superior protection compared to circulating memory T cells. Here we describe a simple and non-inflammatory vaccine strategy that enables the establishment of a protective memory T-cell pool within peripheral tissue. The female genital tract, which is a portal of entry for sexually transmitted infections, is an immunologically restrictive tissue that prevents entry of activated T cells in the absence of inflammation or infection. To overcome this obstacle, we developed a vaccine strategy that we term ‘prime and pull’ to establish local tissue-resident memory T cells at a site of potential viral exposure. This approach relies on two steps: conventional parenteral vaccination to elicit systemic T-cell responses (prime), followed by recruitment of activated T cells by means of topical chemokine application to the restrictive genital tract (pull), where such T cells establish a long-term niche and mediate protective immunity. In mice, prime and pull protocol reduces the spread of infectious herpes simplex virus 2 into the sensory neurons and prevents development of clinical disease. These results reveal a promising vaccination strategy against herpes simplex virus 2, and potentially against other sexually transmitted infections such as human immunodeficiency virus.

原文地址

http://www.nature.com/nature/journal/v491/n7424/full/nature11522.html

 

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