Nachbagauer Raffael, Salaun Bruno, Stadlbauer Daniel, Behzadi Mohammad A, Friel Damien, Rajabhathor Arvind, Choi Angela, Albrecht Randy A, Debois Muriel, García-Sastre Adolfo, Rouxel Ronan N, Sun Weina, Palese Peter, Mallett Corey P, Innis Bruce L, Krammer Florian, Claeys Carine
1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY USA.
2GSK, Rixensart, Belgium.
NPJ Vaccines. 2019 Dec 6;4:51. doi: 10.1038/s41541-019-0147-z. eCollection 2019.
Licensed influenza virus vaccines target the head domain of the hemagglutinin (HA) glycoprotein which undergoes constant antigenic drift. The highly conserved HA stalk domain is an attractive target to increase immunologic breadth required for universal influenza virus vaccines. We tested the hypothesis that immunization with a pandemic influenza virus vaccine boosts pre-existing anti-stalk antibodies. We used chimeric cH6/1, full length H2 and H18 HA antigens in an ELISA to measure anti-stalk antibodies in recipients participating in clinical trials of A/H1N1, A/H5N1 and A/H9N2 vaccines. The vaccines induced high titers of anti-H1 stalk antibodies in adults and children, with higher titers elicited by AS03-adjuvanted vaccines. We also observed cross-reactivity to H2 and H18 HAs. The A/H9N2 vaccine elicited plasmablast and memory B-cell responses. Post-vaccination serum from vaccinees protected mice against lethal challenge with cH6/1N5 and cH5/3N4 viruses. These findings support the concept of a chimeric HA stalk-based universal influenza virus vaccine. clinicaltrials.gov: NCT02415842.
获得许可的流感病毒疫苗针对的是血凝素（HA）糖蛋白的头部结构域，该结构域会不断发生抗原漂移。高度保守的HA茎部结构域是增加通用流感病毒疫苗所需免疫广度的一个有吸引力的靶点。我们检验了大流行性流感病毒疫苗免疫可增强预先存在的抗茎部抗体这一假设。我们在酶联免疫吸附测定（ELISA）中使用嵌合cH6/1、全长H2和H18 HA抗原，以测量参与甲型H1N1、甲型H5N1和甲型H9N2疫苗临床试验的受试者体内的抗茎部抗体。这些疫苗在成人和儿童中诱导产生了高滴度的抗H1茎部抗体，含AS03佐剂的疫苗诱导产生的滴度更高。我们还观察到对H2和H18 HA的交叉反应性。甲型H9N2疫苗引发了浆母细胞和记忆B细胞反应。接种疫苗者接种疫苗后的血清保护小鼠免受cH6/1N5和cH5/3N4病毒的致死性攻击。这些发现支持了基于嵌合HA茎部的通用流感病毒疫苗的概念。临床试验注册号：NCT02415842。
