Clemens E Bridie, van de Sandt Carolien, Wong Sook San, Wakim Linda M, Valkenburg Sophie A
Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Vaccines (Basel). 2018 Mar 26;6(2):18. doi: 10.3390/vaccines6020018.
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.
利用T细胞的新一代疫苗有可能克服当前流感疫苗的局限性，后者依靠抗体提供狭窄的亚型特异性保护，且容易与流行毒株发生抗原不匹配。动物模型的证据表明，T细胞可提供异源亚型保护，对流感病毒感染的免疫控制至关重要。这为设计一种能够针对多种流感病毒毒株和亚型引发免疫反应的通用疫苗带来了希望。然而，实现通用T细胞疫苗存在多个障碍。总体而言，主要问题包括：将人体临床研究结果外推、植入持久有效的T细胞驻留记忆（Trm）、人群人类白细胞抗原（HLA）覆盖范围，以及T细胞介导的免疫逃逸可能性。在自然感染期间需要更多全面的人体临床数据，以验证T细胞在无抗体情况下感染过程中所起的保护作用。此外，关于最佳保护所需T细胞的部位、寿命和持续时间、数量以及表型，仍然存在基本问题。需要标准化的实验方法，并最终简化商业检测方法，以评估外周血流感特异性T细胞反应，以便对T细胞作为预防流感感染的保护相关性进行大规模临床研究。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，这种保护可能无法提供无菌免疫，但可以保护个体免受严重疾病侵害，缩短感染时间，并有可能减少社区内的传播。因此，应在大流行防范和人畜共患感染的背景下，结合改进的抗体疫苗靶向方法，考虑提高T细胞疫苗可能提供的护理标准。当前的大流行疫苗防范措施和正在进行的临床试验未充分利用T细胞诱导疫苗，这反映出关于如何、何时、何地以及需要哪些T细胞来对抗流感病毒感染仍有无数问题。本综述旨在将T细胞生物学的基本原理与人体临床数据结合起来，这些数据对于实施利用T细胞力量的通用流感疫苗是需要考虑的。
