Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza Vaccine.
Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza Vaccine.
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DOI：
10.3390/vaccines6020018
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发表时间：
2018-03-26
期刊：
影响因子：
7.8
通讯作者：
Valkenburg SA
中科院分区：
文献类型：
--
作者：
Clemens EB;van de Sandt C;Wong SS;Wakim LM;Valkenburg SA
利用T细胞的下一代疫苗有可能克服当前流感疫苗的局限性。当前流感疫苗依赖抗体提供窄亚型特异性保护，并且容易与流行毒株发生抗原不匹配。来自动物模型的证据表明，T细胞可以提供异亚型保护，对流感病毒感染的免疫控制至关重要。这为设计一种能够预防多种流感病毒株和亚型的通用疫苗提供了希望。然而，实现通用T细胞疫苗存在多种障碍。总的来说，主要关注的是：推断人类临床研究，播种持久有效的T细胞驻留记忆（Trm），群体人类白细胞抗原（HLA）覆盖，以及T细胞介导的免疫逃逸的潜力。在自然感染期间，需要进一步全面的人类临床数据来验证T细胞在无抗体感染期间发挥的保护作用。此外，关于最佳保护所需的T细胞的位置、寿命和持续时间、数量和表型等基本问题仍然存在。需要标准化的实验方法和最终简化的商业分析来评估外周流感特异性T细胞反应，以便进行T细胞与流感感染保护相关的更大规模临床研究。T细胞诱导疫苗的设计和实施将需要就社区可接受的保护水平达成共识，这可能不能提供绝育免疫，但可以保护个人免受严重疾病的侵害，缩短感染时间，并可能减少社区中的传播。因此，在大流行防范和人畜共患感染的背景下，应考虑提高T细胞疫苗可能提供的护理标准，并与改进的抗体疫苗靶向方法相结合。目前的大流行疫苗准备措施和正在进行的临床试验没有充分利用T细胞诱导疫苗，这反映了关于如何、何时、何地以及需要哪种T细胞来对抗流感病毒感染的无数问题。这篇综述的目的是将T细胞生物学的基本原理与人类临床数据结合起来，需要考虑利用T细胞的力量来实施抗流感的通用疫苗。
Next-generation vaccines that utilize T cells could potentially overcome the limitations of current influenza vaccines that rely on antibodies to provide narrow subtype-specific protection and are prone to antigenic mismatch with circulating strains. Evidence from animal models shows that T cells can provide heterosubtypic protection and are crucial for immune control of influenza virus infections. This has provided hope for the design of a universal vaccine able to prime against diverse influenza virus strains and subtypes. However, multiple hurdles exist for the realisation of a universal T cell vaccine. Overall primary concerns are: extrapolating human clinical studies, seeding durable effective T cell resident memory (Trm), population human leucocyte antigen (HLA) coverage, and the potential for T cell-mediated immune escape. Further comprehensive human clinical data is needed during natural infection to validate the protective role T cells play during infection in the absence of antibodies. Furthermore, fundamental questions still exist regarding the site, longevity and duration, quantity, and phenotype of T cells needed for optimal protection. Standardised experimental methods, and eventually simplified commercial assays, to assess peripheral influenza-specific T cell responses are needed for larger-scale clinical studies of T cells as a correlate of protection against influenza infection. The design and implementation of a T cell-inducing vaccine will require a consensus on the level of protection acceptable in the community, which may not provide sterilizing immunity but could protect the individual from severe disease, reduce the length of infection, and potentially reduce transmission in the community. Therefore, increasing the standard of care potentially offered by T cell vaccines should be considered in the context of pandemic preparedness and zoonotic infections, and in combination with improved antibody vaccine targeting methods. Current pandemic vaccine preparedness measures and ongoing clinical trials under-utilise T cell-inducing vaccines, reflecting the myriad questions that remain about how, when, where, and which T cells are needed to fight influenza virus infection. This review aims to bring together basic fundamentals of T cell biology with human clinical data, which need to be considered for the implementation of a universal vaccine against influenza that harnesses the power of T cells.
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影响因子：
56.9
作者：
Arstila, TP;Casrouge, A;Kourilsky, P
通讯作者：
Kourilsky, P
影响因子：
15.3
作者：
BURROWS, SR;SILINS, SL;ARGAET, VP
通讯作者：
ARGAET, VP
影响因子：
4.8
作者：
Ambrose CS;Levin MJ
通讯作者：
Levin MJ
影响因子：
3.7
作者：
Bolton, Kirsty J.;McCaw, James M.;McVernon, Jodie
通讯作者：
McVernon, Jodie
DOI：
10.1093/cid/ciq015
发表时间：
2011-01-01
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Berthoud TK;Hamill M;Lillie PJ;Hwenda L;Collins KA;Ewer KJ;Milicic A;Poyntz HC;Lambe T;Fletcher HA;Hill AV;Gilbert SC
通讯作者：
Gilbert SC