Patel Manish M, York Ian A, Monto Arnold S, Thompson Mark G, Fry Alicia M
Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Lancet Microbe. 2021 Dec;2(12):e715-e725. doi: 10.1016/S2666-5247(21)00180-4. Epub 2021 Sep 24.
Sterilising immunity that blocks infection for life, and thus prevents illness after infection, is the ultimate goal for vaccines. Neither influenza infection nor vaccination provide sterilising immunity. Mutations during influenza viral genome replication result in the emergence of viruses that evade immunity and cause reinfections. Waning of immunity also results in reinfections to homologous influenza viruses. However, immunity might limit the severity of disease after infection or vaccination (ie, immunoattenuation). We provide a comprehensive examination of experimental and observational peer reviewed evidence since 1933, when the first influenza virus was isolated, on whether immunity blocks subsequent infection or attenuates illness. Although an abundance of experimental evidence supports immunoattenuation, clinical evidence is rudimentary and conflicting. To the extent that immunoattenuation occurs, understanding the varied pathways to illness, pathogenesis, clinical manifestations, and correlates of attenuation can improve the design and evaluation of influenza vaccines. By elucidating the mechanisms of immunoattenuation and phenotypes of illness, we clarify ambiguities and identify unmet needs that, if addressed with priority, could strategically improve the design of vaccines for the prevention of influenza.
终身阻断感染从而预防感染后发病的灭菌免疫是疫苗的最终目标。流感感染和接种疫苗都无法提供灭菌免疫。流感病毒基因组复制过程中的突变会导致病毒出现，这些病毒能够逃避免疫并引发再次感染。免疫力的减弱也会导致对同源流感病毒的再次感染。然而，免疫可能会限制感染或接种疫苗后疾病的严重程度（即免疫衰减）。我们全面审视了自1933年分离出第一株流感病毒以来的实验性和观察性同行评议证据，以探讨免疫是会阻断后续感染还是减轻疾病。尽管大量实验证据支持免疫衰减，但临床证据尚不充分且相互矛盾。就免疫衰减的发生程度而言，了解疾病的不同发病途径、发病机制、临床表现以及衰减的相关因素，有助于改进流感疫苗的设计和评估。通过阐明免疫衰减的机制和疾病的表型，我们澄清了模糊之处，并确定了未满足的需求，若能优先解决这些需求，可从战略上改进预防流感疫苗的设计。
