Boosted Influenza-Specific T Cell Responses after H5N1 Pandemic Live Attenuated Influenza Virus Vaccination.
Boosted Influenza-Specific T Cell Responses after H5N1 Pandemic Live Attenuated Influenza Virus Vaccination.
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DOI：
10.3389/fimmu.2015.00287
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发表时间：
2015
影响因子：
7.3
通讯作者：
Dong T
中科院分区：
文献类型：
--
作者：
Peng Y;Wang B;Talaat K;Karron R;Powell TJ;Zeng H;Dong D;Luke CJ;McMichael A;Subbarao K;Dong T
在I期临床试验中，在A/安阿伯冷适应疫苗骨架上携带禽流感H5 N1血凝素（HA）和NA基因的H5 N1大流行性减毒活流感病毒（pLAIV）VN 2004疫苗显示出非常有限的复制。我们评估了对H5 N1 pLAIV疫苗接种的T细胞应答，并评估了预先存在的T细胞应答，以确定它们是否与H5 N1 pLAIV的限制性复制相关。使用跨越整个H5 N1蛋白质组和相关季节性H1N1和H3 N2病毒的HA蛋白的重叠肽库进行ELISPOT测定。我们检测了来自21名接受两剂H5 N1 pLAIV的研究受试者的储存的外周血单核细胞（PBMC）。分别在第一次和第二次pLAIV疫苗剂量之前1天和之后7天收集PBMC。对保守的内部蛋白M和NP的T细胞应答通过疫苗接种显著增强（p = 0.036）。此外，H5 N1 pLAIV似乎优先刺激和增强预先存在的季节性流感病毒HA特异性T细胞应答，其显示与H5 HA的低交叉反应性。我们通过T细胞克隆证实了这一观察结果，并鉴定了一种新的HA特异性表位。然而，我们没有发现任何证据表明预先存在的T细胞阻止了pLAIV的复制和摄取。我们发现，交叉反应性T细胞反应可以通过pLAIV增强，而不管抗体的诱导。“原始抗原罪”现象在志愿者亚群中的影响，季节性流感特异性而非H5 N1特异性T细胞应答的优先扩增值得进一步研究。
In a phase I clinical trial, a H5N1 pandemic live attenuated influenza virus (pLAIV) VN2004 vaccine bearing avian influenza H5N1 hemagglutinin (HA) and NA genes on the A/Ann Arbor cold-adapted vaccine backbone displayed very restricted replication. We evaluated T cell responses to H5N1 pLAIV vaccination and assessed pre-existing T cell responses to determine whether they were associated with restricted replication of the H5N1 pLAIV. ELISPOT assays were performed using pools of overlapping peptides spanning the entire H5N1 proteome and the HA proteins of relevant seasonal H1N1 and H3N2 viruses. We tested stored peripheral blood mononuclear cells (PBMCs) from 21 study subjects who received two doses of the H5N1 pLAIV. The PBMCs were collected 1 day before and 7 days after the first and second pLAIV vaccine doses, respectively. T cell responses to conserved internal proteins M and NP were significantly boosted by vaccination (p = 0.036). In addition, H5N1 pLAIV appeared to preferentially stimulate and boost pre-existing seasonal influenza virus HA-specific T cell responses that showed low cross-reactivity with the H5 HA. We confirmed this observation by T cell cloning and identified a novel HA-specific epitope. However, we did not find any evidence that pre-existing T cells prevented pLAIV replication and take. We found that cross-reactive T cell responses could be boosted by pLAIV regardless of the induction of antibody. The impact of the “original antigenic sin” phenomenon in a subset of volunteers, with preferential expansion of seasonal influenza-specific but not H5N1-specific T cell responses merits further investigation.
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