Boosting of Cross-Reactive and Protection-Associated T Cells in Children After Live Attenuated Influenza Vaccination
Boosting of Cross-Reactive and Protection-Associated T Cells in Children After Live Attenuated Influenza Vaccination
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DOI：
10.1093/infdis/jix165
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发表时间：
2017-05-15
影响因子：
6.4
通讯作者：
Cox, Rebecca J.
中科院分区：
文献类型：
--
作者：
Mohn, Kristin G. I.;Zhou, Fan;Cox, Rebecca J.
背景。减毒流感活疫苗（LAIVs）刺激多方面的免疫反应，包括细胞免疫，这可能对新出现的毒株提供保护。这项研究证明了laiv可以促进儿童体内预先存在的交叉反应性T细胞，从而抵抗儿童没有接触过的遗传多样性甲型流感病毒（IAV）毒株。本研究采用荧光免疫斑点法（FluoroSpot）研究了14例三价laiv疫苗接种儿童的长期交叉反应性t细胞反应，采用异种H1N1和H3N2 iav和CD8（+）肽从内部蛋白（基质蛋白1 [M1]、核蛋白[NP]、聚合酶碱性蛋白1 [PB1]）中提取。用血凝抑制试验测定血清抗体反应。在接种疫苗前和接种疫苗后1年内采集血样。在大多数儿童中发现了先前存在的对遗传多样性IAV株的交叉反应性T细胞，在接受LAIV后，其中50%的儿童进一步提高了这种细胞。对这些T细胞的进一步分析显示，CD8+ T细胞显著增加，主要以np特异性反应为主。接种LAIV后，年龄最小的儿童的t细胞反应增加最多。LAIV在儿童中促进持久的交叉反应性t细胞反应，可能在人群水平上具有临床保护作用。LAIV可能是研制通用流感疫苗的第一步。
Background. Live attenuated influenza vaccines (LAIVs) stimulate a multifaceted immune response including cellular immunity, which may provide protection against newly emerging strains. This study shows proof of concept that LAIVs boost preexisting, cross-reactive T cells in children to genetically diverse influenza A virus (IAV) strains to which the children had not been exposed.Methods. We studied the long-term cross-reactive T-cell response in 14 trivalent LAIV-vaccinated children using the fluorescent immunospot assay (FluoroSpot) with heterologous H1N1 and H3N2 IAVs and CD8(+) peptides from the internal proteins (matrix protein 1 [M1], nucleoprotein [NP], polymerase basic protein 1 [PB1]). Serum antibody responses were determined by means of hemagglutination inhibition assay. Blood samples were collected before vaccination and up to 1 year after vaccination.Results. Preexisting cross-reactive T cells to genetically diverse IAV strains were found in the majority of the children, which were further boosted in 50% of them after receipt of LAIV. Further analyses of these T cells showed significant increases in CD8+ T cells, mainly dominated by NP-specific responses. After vaccination with LAIV, the youngest children showed the highest increase in T-cell responses.Conclusion. LAIV boosts durable, cross-reactive T-cell responses in children and may have a clinically protective effect at the population level. LAIV may be a first step toward the desired universal influenza vaccine.