Liu Xuejie, Zhao Tianyi, Wang Liangliang, Li Minchao, Sun Caijun, Shu Yuelong
School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China.
Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Microbiol. 2022 Sep 29;13:1014122. doi: 10.3389/fmicb.2022.1014122. eCollection 2022.
Vaccination is the most effective means of protecting people from influenza virus infection. The effectiveness of existing vaccines is very limited due to antigenic drift of the influenza virus. Therefore, there is a requirement to develop a universal vaccine that provides broad and long-lasting protection against influenza. CD8+ T-cell response played a vital role in controlling influenza virus infection, reducing viral load, and less clinical syndrome. In this study, we optimized the HA sequences of human seasonal influenza viruses (H1N1, H3N2, Victoria, and Yamagata) by designing multivalent vaccine antigen sets using a mosaic vaccine design strategy and genetic algorithms, and designed an HA mosaic cocktail containing the most potential CTL epitopes of seasonal influenza viruses. We then tested the recombinant mosaic antigen, which has a significant number of potential T-cell epitopes. Results from genetic evolutionary analyses and 3D structural simulations demonstrated its potential to be an effective immunogen. In addition, we have modified an existing neutralizing antibody-based seasonal influenza virus vaccine to include a component that activates cross-protective T cells, which would provide an attractive strategy for improving human protection against seasonal influenza virus drift and mutation and provide an idea for the development of a rationally designed influenza vaccine targeting T lymphocyte immunity.
接种疫苗是保护人们免受流感病毒感染的最有效手段。由于流感病毒的抗原漂移，现有疫苗的有效性非常有限。因此，需要开发一种能提供广泛且持久的流感防护的通用疫苗。CD8 + T细胞反应在控制流感病毒感染、降低病毒载量以及减轻临床症状方面发挥着至关重要的作用。在本研究中，我们通过使用嵌合疫苗设计策略和遗传算法设计多价疫苗抗原组，优化了人类季节性流感病毒（H1N1、H3N2、维多利亚系和山形系）的血凝素（HA）序列，并设计了一种包含季节性流感病毒最具潜力的细胞毒性T淋巴细胞（CTL）表位的HA嵌合鸡尾酒疫苗。然后，我们测试了具有大量潜在T细胞表位的重组嵌合抗原。遗传进化分析和三维结构模拟结果表明其有潜力成为一种有效的免疫原。此外，我们对现有的基于中和抗体的季节性流感病毒疫苗进行了改良，使其包含一种能激活交叉保护性T细胞的成分，这将为提高人类对季节性流感病毒漂移和突变的防护提供一种有吸引力的策略，并为开发针对T淋巴细胞免疫的合理设计的流感疫苗提供思路。
