Del Campo Judith, Pizzorno Andres, Djebali Sophia, Bouley Julien, Haller Marjorie, Pérez-Vargas Jimena, Lina Bruno, Boivin Guy, Hamelin Marie-Eve, Nicolas Florence, Le Vert Alexandre, Leverrier Yann, Rosa-Calatrava Manuel, Marvel Jacqueline, Hill Fergal
Osivax, 99, rue de Gerland, 69007 Lyon, France.
2Virologie et Pathologie Humaine - VirPath Team, Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, École Normale Supérieure de Lyon, Université Claude Bernard Lyon 1. Université de Lyon, Lyon, F- 69008 France.
NPJ Vaccines. 2019 Jan 23;4:4. doi: 10.1038/s41541-019-0098-4. eCollection 2019.
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.
灭活流感疫苗（IIV）缺乏广泛的效力。针对保守内部抗原核蛋白（NP）的细胞免疫与预防大流行和季节性流感相关，因此有可能扩大疫苗效力。我们开发了OVX836，一种基于寡聚化NP的重组蛋白疫苗，与NP相比，它显示出树突状细胞摄取增加和免疫原性增强。用OVX836对小鼠进行肌肉内免疫诱导了强烈的NP特异性CD4+和CD8+T细胞全身反应，并在肺实质中建立了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病毒亚型的病毒攻击，这些亚型相隔数十年分离，并且诱导病毒载量降低。当与IIV联合给药时，OVX836在降低肺病毒载量方面甚至更有效。
