Vaccination remains our main defence against influenza, which causes substantial annual mortality and poses a serious pandemic threat. Influenza virus evades immunity by rapidly changing its surface antigens but, even when the vaccine is well matched to the current circulating virus strains, influenza vaccines are not as effective as many other vaccines. Influenza vaccine development has traditionally focused on the induction of protective antibodies, but there is mounting evidence that T cell responses are also protective against influenza. Thus, future vaccines designed to promote both broad T cell effector functions and antibodies may provide enhanced protection. As we discuss, such vaccines present several challenges that require new strategic and economic considerations. Vaccine-induced T cells relevant to protection may reside in the lungs or lymphoid tissues, requiring more invasive assays to assess the immunogenicity of vaccine candidates. T cell functions may contain and resolve infection rather than completely prevent infection and early illness, requiring vaccine effectiveness to be assessed based on the prevention of severe disease and death rather than symptomatic infection. It can be complex and costly to measure T cell responses and infrequent clinical outcomes, and thus innovations in clinical trial design are needed for economic reasons. Nevertheless, the goal of more effective influenza vaccines justifies renewed and intensive efforts.

疫苗接种仍然是我们预防流感的主要手段，流感每年导致大量死亡，并构成严重的大流行威胁。流感病毒通过快速改变其表面抗原来逃避免疫，但是，即使疫苗与当前流行的病毒株很好匹配，流感疫苗也不像许多其他疫苗那么有效。传统上，流感疫苗的开发重点是诱导保护性抗体，但越来越多的证据表明，T 细胞反应也能预防流感。因此，未来旨在促进广泛 T 细胞效应功能和抗体的疫苗可能会提供增强的保护。正如我们所讨论的，此类疫苗提出了一些挑战，需要新的战略和经济考虑。与保护相关的疫苗诱导的 T 细胞可能驻留在肺部或淋巴组织中，需要更具侵入性的测定来评估候选疫苗的免疫原性。 T细胞功能可能包含并解决感染，而不是完全预防感染和早期疾病，因此需要根据预防严重疾病和死亡而不是症状感染来评估疫苗的有效性。测量 T 细胞反应和罕见的临床结果可能非常复杂且成本高昂，因此出于经济原因需要临床试验设计的创新。尽管如此，更有效的流感疫苗的目标证明了重新加强努力的必要性。