Vaccine-induced systemic and mucosal T cell immunity to SARS-CoV-2 viral variants.
Vaccine-induced systemic and mucosal T cell immunity to SARS-CoV-2 viral variants.
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疫苗诱导的针对SARS-CoV-2病毒变体的全身和粘膜T细胞免疫。
DOI：
10.1073/pnas.2118312119
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发表时间：
2022-05-17
影响因子：
11.1
通讯作者：
Suresh, M.
中科院分区：
文献类型：
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作者：
Kingstad-Bakke, Brock;Lee, Woojong;Chandrasekar, Shaswath S.;Gasper, David J.;Salas-Quinchucua, Cristhian;Cleven, Thomas;Sullivan, Jeremy A.;Talaat, Adel;Osorio, Jorge E.;Suresh, M.
第一代COVID-19疫苗诱导的免疫力可能无法提供有效和持久的保护，原因是免疫力减弱或抗体对新变体的交叉反应性差。通常，T细胞识别保守的不可突变的病毒表位，基于T细胞的疫苗的开发可能会提供对SARS-CoV-2变体的广泛免疫。在这项研究中，我们表明，佐剂刺突蛋白为基础的实验疫苗引起了有效的呼吸或全身的CD 4和CD 8 T细胞的记忆和保护对SARS冠状病毒-2，在病毒中和抗体的情况下。因此，开发基于T细胞的疫苗可能是预防抗体逃逸SARS-CoV-2变体的关键，这些变体可能会克服当前疫苗诱导的免疫力。第一代COVID-19疫苗在减轻严重疾病和住院方面一直有效，但反复出现的感染浪潮与SARS-CoV-2变异的出现有关，这些变异显示出渐进的逃避抗体的能力，导致疫苗有效性降低。疫苗诱导的粘膜或全身记忆T细胞在多大程度上保护免受这种抗体逃避性SARS-CoV-2变体的影响仍然是我们寻求广泛保护性疫苗的关键知识差距。使用佐剂刺突蛋白为基础的疫苗，引发有效的T细胞反应，我们评估是否系统或肺部驻留的CD 4和CD 8 T细胞保护SARS-CoV-2变异体在存在或不存在病毒中和抗体。我们发现，1）粘膜或肠胃外免疫导致有效的病毒控制，并且在有或没有中和抗体的情况下保护免受肺部病理，2）在有效中和攻击病毒的抗体存在下，粘膜记忆CD 8 T细胞提供的保护在很大程度上是多余的，和3）“无助的”粘膜记忆CD 8 T细胞在没有CD 4 T细胞和中和抗体的情况下对同源SARS-CoV-2没有保护作用。然而，值得注意的是，在缺乏可检测到的病毒中和抗体的情况下，系统性或肺部驻留的记忆性CD 4和“辅助”CD 8 T细胞提供了针对相对抗体抗性的B1.351（β）变体的有效保护，而没有肺部免疫病理学。因此，诱导针对保守表位的全身和粘膜记忆T细胞可能是一种有效的策略，以防止SARS-CoV-2变异，逃避中和抗体。这项工作的机制见解在T细胞靶向免疫调节或广泛保护SARS-CoV-2疫苗的开发中具有重要意义。
Immunity induced by the first-generation COVID-19 vaccines may not provide effective and durable protection, either due to waning immunity or due to poor antibody cross-reactivity to new variants. Typically, T cells recognize conserved nonmutable viral epitopes and development of T cell–based vaccines might provide broad immunity to SARS-CoV-2 variants. In this study, we show that adjuvanted spike protein–based experimental vaccines elicited potent respiratory or systemic CD4 and CD8 T cell memory and protected against SARS-CoV-2, in the absence of virus-neutralizing antibodies. Thus, development of T cell–based vaccines might be key to protect against antibody-escape SARS-CoV-2 variants that can potentially overcome immunity induced by current vaccines. The first-generation COVID-19 vaccines have been effective in mitigating severe illness and hospitalization, but recurring waves of infections are associated with the emergence of SARS-CoV-2 variants that display progressive abilities to evade antibodies, leading to diminished vaccine effectiveness. The lack of clarity on the extent to which vaccine-elicited mucosal or systemic memory T cells protect against such antibody-evasive SARS-CoV-2 variants remains a critical knowledge gap in our quest for broadly protective vaccines. Using adjuvanted spike protein–based vaccines that elicit potent T cell responses, we assessed whether systemic or lung-resident CD4 and CD8 T cells protected against SARS-CoV-2 variants in the presence or absence of virus-neutralizing antibodies. We found that 1) mucosal or parenteral immunization led to effective viral control and protected against lung pathology with or without neutralizing antibodies, 2) protection afforded by mucosal memory CD8 T cells was largely redundant in the presence of antibodies that effectively neutralized the challenge virus, and 3) “unhelped” mucosal memory CD8 T cells provided no protection against the homologous SARS-CoV-2 without CD4 T cells and neutralizing antibodies. Significantly, however, in the absence of detectable virus-neutralizing antibodies, systemic or lung-resident memory CD4 and “helped” CD8 T cells provided effective protection against the relatively antibody-resistant B1.351 (β) variant, without lung immunopathology. Thus, induction of systemic and mucosal memory T cells directed against conserved epitopes might be an effective strategy to protect against SARS-CoV-2 variants that evade neutralizing antibodies. Mechanistic insights from this work have significant implications in the development of T cell–targeted immunomodulation or broadly protective SARS-CoV-2 vaccines.
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影响因子：
64.5
作者：
Hoffmann M;Arora P;Groß R;Seidel A;Hörnich BF;Hahn AS;Krüger N;Graichen L;Hofmann-Winkler H;Kempf A;Winkler MS;Schulz S;Jäck HM;Jahrsdörfer B;Schrezenmeier H;Müller M;Kleger A;Münch J;Pöhlmann S
通讯作者：
Pöhlmann S
影响因子：
100.3
作者：
Chen, Zeyu;John Wherry, E.
通讯作者：
John Wherry, E.
影响因子：
6.7
作者：
Gasper DJ;Neldner B;Plisch EH;Rustom H;Carrow E;Imai H;Kawaoka Y;Suresh M
通讯作者：
Suresh M
影响因子：
64.8
作者：
Alter G;Yu J;Liu J;Chandrashekar A;Borducchi EN;Tostanoski LH;McMahan K;Jacob-Dolan C;Martinez DR;Chang A;Anioke T;Lifton M;Nkolola J;Stephenson KE;Atyeo C;Shin S;Fields P;Kaplan I;Robins H;Amanat F;Krammer F;Baric RS;Le Gars M;Sadoff J;de Groot AM;Heerwegh D;Struyf F;Douoguih M;van Hoof J;Schuitemaker H;Barouch DH
通讯作者：
Barouch DH
DOI：
10.1038/nri3567
发表时间：
2014-01
期刊：
Nature reviews. Immunology
影响因子：
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作者：
通讯作者：
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