Nebraska Center for Virology and Department of Animal Science, University of Nebraska, Lincoln, Nebraska, USA.
Department of Veterinary Pathology, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea.
Vet Microbiol. 2019 Dec;239:108451. doi: 10.1016/j.vetmic.2019.108451. Epub 2019 Oct 12.
The substantial genetic diversity exhibited by influenza A viruses of swine (IAV-S) represents the main challenge for the development of a broadly protective vaccine against this important pathogen. The consensus vaccine immunogen has proven an effective vaccinology approach to overcome the extraordinary genetic diversity of RNA viruses. In this project, we sought to determine if a consensus IAV-S hemagglutinin (HA) immunogen would elicit broadly protective immunity in pigs. To address this question, a consensus HA gene (designated H3-CON.1) was generated from a set of 1,112 H3 sequences of IAV-S recorded in GenBank from 2011 to 2015. The consensus HA gene and a HA gene of a naturally occurring H3N2 IAV-S strain (designated H3-TX98) were expressed using the baculovirus expression system and emulsified in an oil-in-water adjuvant to be used for vaccination. Pigs vaccinated with H3-CON.1 immunogen elicited broader levels of cross-reactive neutralizing antibodies and interferon gamma secreting cells than those vaccinated with H3-TX98 immunogen. After challenge infection with a fully infectious H3N2 IAV-S isolate, the H3-CON.1-vaccinated pigs shed significantly lower levels of virus in their nasal secretions than the H3-TX98-vaccinated pigs. Collectively, our data provide a proof-of-evidence that the consensus immunogen approach may be effectively employed to develop a broadly protective vaccine against IAV-S.
猪流感病毒 (IAV-S) 表现出的大量遗传多样性是开发针对这种重要病原体的广泛保护疫苗的主要挑战。共识疫苗免疫原已被证明是克服 RNA 病毒非凡遗传多样性的有效疫苗学方法。在这个项目中,我们试图确定共识 IAV-S 血凝素 (HA) 免疫原是否会在猪中引发广泛的保护免疫。为了解决这个问题,我们从 2011 年至 2015 年在 GenBank 中记录的 1,112 个 IAV-S H3 序列中生成了一个共识 HA 基因(指定为 H3-CON.1)。共识 HA 基因和源自自然发生的 H3N2 IAV-S 株的 HA 基因(指定为 H3-TX98)使用杆状病毒表达系统表达,并在油包水佐剂中乳化,用于疫苗接种。用 H3-CON.1 免疫原接种的猪比用 H3-TX98 免疫原接种的猪产生了更广泛的交叉反应性中和抗体和干扰素γ分泌细胞。用完全传染性 H3N2 IAV-S 分离株进行攻毒感染后,H3-CON.1 疫苗接种的猪在鼻腔分泌物中的病毒载量明显低于 H3-TX98 疫苗接种的猪。总的来说,我们的数据提供了证据证明,共识免疫原方法可有效用于开发针对 IAV-S 的广泛保护疫苗。