Airway Memory CD4(+) T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses.
Airway Memory CD4(+) T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses.
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DOI：
10.1016/j.immuni.2016.05.006
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发表时间：
2016-06-21
期刊：
影响因子：
32.4
通讯作者：
Perlman S
中科院分区：
文献类型：
--
作者：
Zhao J;Zhao J;Mangalam AK;Channappanavar R;Fett C;Meyerholz DK;Agnihothram S;Baric RS;David CS;Perlman S
两种人畜共患冠状病毒（CoV）--SARS-CoV和MERS-CoV--已经跨物种引起严重的人类呼吸道疾病。在这里，我们表明，诱导气道记忆CD 4 + T细胞特异性的SARS-CoV和MERS-CoV共享的保守表位是一个潜在的策略，开发泛冠状病毒疫苗。气道记忆性CD 4 + T细胞在表型和功能上与肺源性细胞不同，对于保护小鼠免受两种CoV的侵害至关重要。保护依赖于干扰素-γ，需要早期诱导强大的先天性和病毒特异性CD 8 + T细胞应答。在SARS-CoV和MERS-CoV感染的人白细胞抗原DR 2和DR 3转基因小鼠中也识别出保守表位，表明在人群中具有潜在的相关性。此外，该表位在人类和蝙蝠CoV（许多人类CoV的祖细胞）之间具有交叉保护性。诱导气道记忆CD 4 + T细胞靶向保守表位的疫苗策略可能在新冠病毒和其他呼吸道病毒爆发的背景下具有广泛的适用性。鼻内而非皮下接种可保护小鼠免受致病性人冠状病毒的侵害保护作用由气道记忆CD 4 + T细胞介导气道记忆CD 4 + T细胞产生的IFN-γ是保护作用所必需的SARS-CoV和MERS-CoV中的保守表位诱导交叉反应性T细胞应答人畜共患冠状病毒在过去10年中出现两次，并导致严重的人类呼吸道疾病。使用甲病毒疫苗载体，Perlman及其同事表明，鼻内疫苗接种诱导气道记忆CD 4 + T细胞应答，保护小鼠免受致命攻击，并与不同的CoV交叉反应。
Two zoonotic coronaviruses (CoVs)—SARS-CoV and MERS-CoV—have crossed species to cause severe human respiratory disease. Here, we showed that induction of airway memory CD4+ T cells specific for a conserved epitope shared by SARS-CoV and MERS-CoV is a potential strategy for developing pan-coronavirus vaccines. Airway memory CD4+ T cells differed phenotypically and functionally from lung-derived cells and were crucial for protection against both CoVs in mice. Protection was dependent on interferon-γ and required early induction of robust innate and virus-specific CD8+ T cell responses. The conserved epitope was also recognized in SARS-CoV- and MERS-CoV-infected human leukocyte antigen DR2 and DR3 transgenic mice, indicating potential relevance in human populations. Additionally, this epitope was cross-protective between human and bat CoVs, the progenitors for many human CoVs. Vaccine strategies that induce airway memory CD4+ T cells targeting conserved epitopes might have broad applicability in the context of new CoVs and other respiratory virus outbreaks. Intranasal but not subcutaneous vaccination protects mice from pathogenic human CoVs Protection is mediated by airway memory CD4+ T cells IFN-γ produced by airway memory CD4+ T cells is required for protection A conserved epitope in SARS-CoV and MERS-CoV induces cross-reactive T cell responses Zoonotic CoVs have emerged twice in the past 10 years and have caused severe human respiratory disease. Using an alphavirus vaccine vector, Perlman and colleagues show that intranasal vaccination induces airway memory CD4+ T cell responses that protect mice from lethal challenge and are cross-reactive to different CoVs.