Human influenza virus challenge identifies cellular correlates of protection for oral vaccination.
Human influenza virus challenge identifies cellular correlates of protection for oral vaccination.
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DOI：
10.1016/j.chom.2021.10.009
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发表时间：
2021-12-08
影响因子：
30.3
通讯作者：
Nolan GP
中科院分区：
文献类型：
--
作者：
McIlwain DR;Chen H;Rahil Z;Bidoki NH;Jiang S;Bjornson Z;Kolhatkar NS;Martinez CJ;Gaudillière B;Hedou J;Mukherjee N;Schürch CM;Trejo A;Affrime M;Bock B;Kim K;Liebowitz D;Aghaeepour N;Tucker SN;Nolan GP
开发性能更好、给药途径更简单的新流感疫苗取决于确定保护的相关性。疫苗引起的细胞相关的保护人类流感尚未得到证实。一项II期双盲随机安慰剂和活性（灭活流感疫苗）对照研究提供了证据，证明基于人腺病毒5的口服流感疫苗片剂（VXA-A1.1）可以保护人类免受H1N1病毒攻击。疫苗引发的细胞免疫应答的质谱细胞术表征鉴定了跨B和T细胞的共享和疫苗类型特异性应答。对于VXA-A1.1，第8天血凝素特异性浆母细胞和整联蛋白α4β7、磷酸化STAT 5阳性或缺乏CD 62 L表达的浆母细胞的丰度与第90天病毒攻击后发生病毒脱落的保护显著相关，并有助于有效的机器学习保护模型。这些发现揭示了疫苗引起的口服流感疫苗保护的细胞相关性的特征。开发具有更大和更广泛功效且更容易施用的流感疫苗需要对保护的相关性有清楚的了解。McIllem和Chen等人使用质谱细胞术鉴定口服流感疫苗片剂（VXA-A1.1）引起的细胞免疫应答，其与保护人类免受流感病毒攻击相关。
Developing new influenza vaccines with improved performance and easier administration routes hinges on defining correlates of protection. Vaccine-elicited cellular correlates of protection for influenza in humans have not yet been demonstrated. A phase 2 double-blind randomized placebo and active (inactivated influenza vaccine) controlled study provides evidence that a human adenovirus 5-based oral influenza vaccine tablet (VXA-A1.1) can protect from H1N1 virus challenge in humans. Mass cytometry characterization of vaccine-elicited cellular immune responses identified shared and vaccine type-specific responses across B and T cells. For VXA-A1.1, the abundance of hemagglutinin-specific plasmablasts and plasmablasts positive for integrin α4β7, phosphorylated STAT5, or lacking expression of CD62L at day 8 were significantly correlated with protection from developing viral shedding following virus challenge at day 90 and contributed to an effective machine learning model of protection. These findings reveal the characteristics of vaccine elicited cellular correlates of protection for an oral influenza vaccine. Developing influenza vaccines with greater and broader efficacy and easier administration requires clear insights into correlates of protection. McIlwain & Chen et al. use mass cytometry to identify cellular immune responses elicited by an oral influenza vaccine tablet (VXA-A1.1) that correlate with protection from influenza virus challenge in humans.
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影响因子：
4.6
作者：
Kim L;Martinez CJ;Hodgson KA;Trager GR;Brandl JR;Sandefer EP;Doll WJ;Liebowitz D;Tucker SN
通讯作者：
Tucker SN
影响因子：
46.9
作者：
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影响因子：
7.3
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影响因子：
3.7
作者：
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通讯作者：
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影响因子：
6.7
作者：
Laidlaw BJ;Decman V;Ali MA;Abt MC;Wolf AI;Monticelli LA;Mozdzanowska K;Angelosanto JM;Artis D;Erikson J;Wherry EJ
通讯作者：
Wherry EJ