Huang Ying, França Monique S, Allen James D, Shi Hua, Ross Ted M
Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA.
Poultry Diagnostic and Research Center, Department of Population Health, University of Georgia, Athens, GA 30602, USA.
Vaccines (Basel). 2021 Jul 16;9(7):793. doi: 10.3390/vaccines9070793.
Vaccination is the best way to prevent influenza virus infections, but the diversity of antigenically distinct isolates is a persistent challenge for vaccine development. In order to conquer the antigenic variability and improve influenza virus vaccine efficacy, our research group has developed computationally optimized broadly reactive antigens (COBRAs) in the form of recombinant hemagglutinins (rHAs) to elicit broader immune responses. However, previous COBRA H1N1 vaccines do not elicit immune responses that neutralize H1N1 virus strains in circulation during the recent years. In order to update our COBRA vaccine, two new candidate COBRA HA vaccines, Y2 and Y4, were generated using a new seasonal-based COBRA methodology derived from H1N1 isolates that circulated during 2013-2019. In this study, the effectiveness of COBRA Y2 and Y4 vaccines were evaluated in mice, and the elicited immune responses were compared to those generated by historical H1 COBRA HA and wild-type H1N1 HA vaccines. Mice vaccinated with the next generation COBRA HA vaccines effectively protected against morbidity and mortality after infection with H1N1 influenza viruses. The antibodies elicited by the COBRA HA vaccines were highly cross-reactive with influenza A (H1N1) pdm09-like viruses isolated from 2009 to 2021, especially with the most recent circulating viruses from 2019 to 2021. Furthermore, viral loads in lungs of mice vaccinated with Y2 and Y4 were dramatically reduced to low or undetectable levels, resulting in minimal lung injury compared to wild-type HA vaccines following H1N1 influenza virus infection.
接种疫苗是预防流感病毒感染的最佳方法，但抗原性不同的分离株的多样性是疫苗开发中持续存在的挑战。为了克服抗原变异性并提高流感病毒疫苗的效力，我们的研究小组开发了重组血凝素（rHA）形式的计算优化的广谱反应性抗原（COBRA），以引发更广泛的免疫反应。然而，以前的COBRA H1N1疫苗未能引发中和近年来流行的H1N1病毒株的免疫反应。为了更新我们的COBRA疫苗，使用源自2013 - 2019年流行的H1N1分离株的基于新季节的COBRA方法，生成了两种新的候选COBRA HA疫苗Y2和Y4。在本研究中，在小鼠中评估了COBRA Y2和Y4疫苗的有效性，并将引发的免疫反应与历史H1 COBRA HA和野生型H1N1 HA疫苗产生的免疫反应进行了比较。用下一代COBRA HA疫苗接种的小鼠在感染H1N1流感病毒后有效地预防了发病和死亡。COBRA HA疫苗引发的抗体与2009年至2021年分离的甲型流感（H1N1）pdm09样病毒具有高度交叉反应性，尤其是与2019年至2021年最近流行的病毒。此外，与H1N1流感病毒感染后的野生型HA疫苗相比，接种Y2和Y4的小鼠肺部的病毒载量显著降低至低水平或无法检测到的水平，导致肺部损伤最小。
