Liu Wen-Chun, Nachbagauer Raffael, Stadlbauer Daniel, Strohmeier Shirin, Solórzano Alicia, Berlanda-Scorza Francesco, Innis Bruce L, García-Sastre Adolfo, Palese Peter, Krammer Florian, Albrecht Randy A
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Vaccines (Basel). 2021 Jan 11;9(1):40. doi: 10.3390/vaccines9010040.
Epidemic or pandemic influenza can annually cause significant morbidity and mortality in humans. We developed novel chimeric hemagglutinin (cHA)-based universal influenza virus vaccines, which contain a conserved HA stalk domain from a 2009 pandemic H1N1 (pH1N1) strain combined with globular head domains from avian influenza A viruses. Our previous reports demonstrated that prime-boost sequential immunizations induced robust antibody responses directed toward the conserved HA stalk domain in ferrets. Herein, we further followed vaccinated animals for one year to compare the efficacy and durability of these vaccines in the preclinical ferret model of influenza. Although all cHA-based immunization regimens induced durable HA stalk-specific and heterosubtypic antibody responses in ferrets, sequential immunization with live-attenuated influenza virus vaccines (LAIV-LAIV) conferred the best protection against upper respiratory tract infection by a pH1N1 influenza A virus. The findings from this study suggest that our sequential immunization strategy for a cHA-based universal influenza virus vaccine provides durable protective humoral and cellular immunity against influenza virus infection.
流行性或大流行性流感每年都会在人类中导致严重的发病和死亡。我们研发了新型的基于嵌合血凝素（cHA）的通用流感病毒疫苗，其包含来自2009年大流行H1N1（pH1N1）毒株的保守HA茎域，并与甲型禽流感病毒的球状头部结构域相结合。我们之前的报告表明，初免-加强序贯免疫在雪貂中诱导了针对保守HA茎域的强烈抗体反应。在此，我们对接种疫苗的动物进一步跟踪了一年，以比较这些疫苗在流感临床前雪貂模型中的疗效和持久性。尽管所有基于cHA的免疫方案在雪貂中都诱导了持久的HA茎特异性和异源亚型抗体反应，但用减毒活流感病毒疫苗（LAIV-LAIV）进行序贯免疫对甲型pH1N1流感病毒引起的上呼吸道感染提供了最佳保护。这项研究的结果表明，我们基于cHA的通用流感病毒疫苗的序贯免疫策略可提供针对流感病毒感染的持久保护性体液和细胞免疫。
