Yu Jieshi, Sreenivasan Chithra, Sheng Zhizhang, Zhai Shao-Lun, Wollman Jared W, Luo Sisi, Huang Chen, Gao Rongyuan, Wang Zhao, Kaushik Radhey S, Christopher-Hennings Jane, Nelson Eric, Hause Ben M, Li Feng, Wang Dan
Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Vaccine. 2023 Oct 6;41(42):6318-6326. doi: 10.1016/j.vaccine.2023.09.007. Epub 2023 Sep 14.
The global distribution and ongoing evolution of type A swine influenza virus (IAV-S) continue to pose significant challenges against developing broadly protective vaccines to control swine influenza. This study focuses on the hemagglutinin (HA) consensus-based approach towards developing a more broadly protective swine influenza vaccine against various H3 strains circulating in domestic pig populations. By computationally analyzing >1000 swine H3 full-length HA sequences, we generated a consensus H3 and expressed it in the context of influenza A WSN/33 reverse genetics system. The derived recombinant chimeric swine influenza virus with the consensus H3 was inactivated and further evaluated as a potential universal vaccine in pigs. The consensus H3 vaccine elicited broadly active hemagglutination inhibition (HI) antibodies against divergent swine H3N2 influenza viruses including human H3N2 variant of concern, and strains belong to genetic clusters IV, IV-A, IV-B, IV-C, IV-D and IV-F. Importantly, vaccinated pigs were completely protected against challenge with a clinical swine H3N2 isolate in that neither viral shedding nor replication in lungs of vaccinated pigs were observed. These findings warrant further study of the consensus H3 vaccine platform for broad protection against diverse swine influenza viruses.
甲型猪流感病毒（IAV-S）的全球分布及不断演变，持续对研发具有广泛保护作用的疫苗以控制猪流感构成重大挑战。本研究聚焦于基于血凝素（HA）的共识方法，以研发一种针对家猪群体中流行的各种H3毒株具有更广泛保护作用的猪流感疫苗。通过对1000多条猪H3全长HA序列进行计算分析，我们生成了一个共识H3，并在甲型流感WSN/33反向遗传学系统中进行表达。将带有共识H3的重组嵌合猪流感病毒灭活，并进一步作为猪用潜在通用疫苗进行评估。该共识H3疫苗引发了针对多种猪H3N2流感病毒（包括关注的人H3N2变异株以及属于遗传簇IV、IV-A、IV-B、IV-C、IV-D和IV-F的毒株）的广泛有效的血凝抑制（HI）抗体。重要的是，接种疫苗的猪完全抵抗了临床猪H3N2分离株的攻击，因为在接种疫苗的猪的肺部未观察到病毒脱落或复制。这些发现值得进一步研究共识H3疫苗平台对多种猪流感病毒的广泛保护作用。
