Petro-Turnquist Erika M, Bullard Brianna L, Pekarek Matthew J, Weaver Eric A
Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, 4240 Fair Street, Lincoln, NE 68504, USA.
Vaccines (Basel). 2022 Jun 10;10(6):926. doi: 10.3390/vaccines10060926.
Several influenza pandemics have occurred in the past century, one of which emerged in 1957 from a zoonotic transmission of H2N2 from an avian reservoir into humans. This pandemic caused 2-4 million deaths and circulated until 1968. Since the disappearance of H2N2 from human populations, there has been waning immunity against H2, and this subtype is not currently incorporated into seasonal vaccines. However, H2 influenza remains a pandemic threat due to consistent circulation in avian reservoirs. Here, we describe a method of pandemic preparedness by creating an adenoviral-vectored centralized consensus vaccine design against human H2 influenza. We also assessed the utility of serotype-switching to enhance the protective immune responses seen with homologous prime-boosting strategies. Immunization with an H2 centralized consensus showed a wide breadth of antibody responses after vaccination, protection against challenge with a divergent human H2 strain, and significantly reduced viral load in the lungs after challenge. Further, serotype switching between two species C adenoviruses enhanced protective antibody titers after heterologous boosting. These data support the notion that an adenoviral-vectored H2 centralized consensus vaccine has the ability to provide broadly cross-reactive immune responses to protect against divergent strains of H2 influenza and prepare for a possible pandemic.
在过去的一个世纪里发生了几次流感大流行，其中一次发生在1957年，H2N2从禽类宿主通过人畜共患病传播给人类。这次大流行导致200万至400万人死亡，并一直传播到1968年。自H2N2从人类群体中消失以来，对H2的免疫力一直在下降，目前季节性疫苗中未包含该亚型。然而，由于H2流感在禽类宿主中持续传播，它仍然是一种大流行威胁。在这里，我们描述了一种大流行防范方法，即通过创建一种针对人类H2流感的腺病毒载体集中式共识疫苗设计。我们还评估了血清型转换在增强同源初免-加强策略所产生的保护性免疫反应方面的效用。用H2集中式共识疫苗免疫后，接种疫苗后显示出广泛的抗体反应，对不同的人类H2毒株攻击具有保护作用，并且在攻击后肺部病毒载量显著降低。此外，两种C型腺病毒之间的血清型转换在异源加强后提高了保护性抗体滴度。这些数据支持这样一种观点，即腺病毒载体H2集中式共识疫苗有能力提供广泛的交叉反应性免疫反应，以保护免受不同H2流感毒株的侵害，并为可能的大流行做好准备。
