OVX836 a recombinant nucleoprotein vaccine inducing cellular responses and protective efficacy against multiple influenza A subtypes
OVX836 a recombinant nucleoprotein vaccine inducing cellular responses and protective efficacy against multiple influenza A subtypes
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DOI：
10.1038/s41541-019-0098-4
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发表时间：
2019-01-23
期刊：
影响因子：
9.2
通讯作者：
Hill, Fergal
中科院分区：
文献类型：
--
作者：
Del Campo, Judith;Pizzorno, Andres;Hill, Fergal
灭活流感疫苗（IIV）缺乏广泛的疗效。对保守的内部抗原核蛋白（NP）的细胞免疫与针对大流行性和季节性流感的保护相关，因此可能具有扩大疫苗效力的潜力。我们开发了OVX836，一种基于寡聚NP的重组蛋白疫苗，与NP相比，其显示出树突状细胞的摄取增加和免疫原性增加。用OVX836肌内免疫小鼠诱导强的NP特异性CD4+和CD8+ T细胞全身应答，并在肺实质中建立CD8+组织记忆T细胞。引人注目的是，OVX836保护小鼠免受三种不同甲型流感亚型的病毒攻击，这些亚型相隔几十年分离，并诱导病毒载量减少。当与IIV联合给药时，OVX 836在降低肺病毒载量方面甚至更有效。
Inactivated influenza vaccines (IIVs) lack broad efficacy. Cellular immunity to a conserved internal antigen, the nucleoprotein (NP), has been correlated to protection against pandemic and seasonal influenza and thus could have the potential to broaden vaccine efficacy. We developed OVX836, a recombinant protein vaccine based on an oligomerized NP, which shows increased uptake by dendritic cells and immunogenicity compared with NP. Intramuscular immunization in mice with OVX836 induced strong NP-specific CD4+ and CD8+ T-cell systemic responses and established CD8+ tissue memory T cells in the lung parenchyma. Strikingly, OVX836 protected mice against viral challenge with three different influenza A subtypes, isolated several decades apart and induced a reduction in viral load. When co-administered with IIV, OVX836 was even more effective in reducing lung viral load.