Center for Vaccines and Immunology, University of Georgiagrid.213876.9, Athens, Georgia, USA.
Department of Infectious Diseases, University of Georgiagrid.213876.9, Athens, Georgia, USA.
J Virol. 2022 Apr 13;96(7):e0165221. doi: 10.1128/jvi.01652-21. Epub 2022 Mar 15.
Commercial influenza virus vaccines often elicit strain-specific immune responses and have difficulties preventing illness caused by antigenically drifted viral variants. In the last 20 years, the H3N2 component of the annual vaccine has been updated nearly twice as often as the H1N1 component, and in 2019, a mismatch between the wild-type (WT) H3N2 vaccine strain and circulating H3N2 influenza strains led to a vaccine efficacy of ∼9%. Modern methods of developing computationally optimized broadly reactive antigens (COBRAs) for H3N2 influenza viruses utilize current viral surveillance information to design more broadly reactive vaccine antigens. Here, 7 new recombinant hemagglutinin (rHA) H3 COBRA hemagglutinin (HA) antigens were evaluated in mice. Subsequently, two candidates, J4 and NG2, were selected for further testing in influenza-preimmune animals based on their ability to elicit broadly reactive antibodies against antigenically drifted H3N2 viral isolates. In the preimmune model, monovalent formulations of J4 and NG2 elicited broadly reactive antibodies against recently circulating H3N2 influenza viruses from 2019. Bivalent mixtures of COBRA H1 and H3 rHA, Y2 + J4, and Y2 + NG2 outperformed multiple WT H1+H3 bivalent rHA mixtures by eliciting seroprotective antibodies against H1N1 and H3N2 isolates from 2009 to 2019. Overall, the newly generated COBRA HA antigens, namely, Y2, J4, and NG2, had the ability to induce broadly reactive antibodies in influenza-naive and preimmune animals in both monovalent and bivalent formulations, and these antigens outperformed H1 and H3 WT rHA vaccine antigens by eliciting seroprotective antibodies against panels of antigenically drifted historical H1N1 and H3N2 vaccine strains from 2009 to 2019. Standard-of-care influenza virus vaccines are composed of a mixture of antigens from different influenza viral subtypes. For the first time, lead COBRA H1 and H3 HA antigens, formulated as a bivalent vaccine, have been investigated in animals with preexisting immunity to influenza viruses. The cocktail of COBRA HA antigens elicited more broadly reactive anti-HA antibodies than those elicited by a comparator bivalent wild-type HA vaccine against H1 and H3 influenza viruses isolated between 2009 and 2019.
商业流感病毒疫苗通常会引发针对特定毒株的免疫反应，并且难以预防抗原漂移的病毒变异株引起的疾病。在过去的 20 年中，每年流感疫苗中的 H3N2 组份的更新频率几乎是 H1N1 组份的两倍，并且在 2019 年，野生型（WT）H3N2 疫苗株与流行的 H3N2 流感株之间不匹配导致疫苗效力约为 9%。用于 H3N2 流感病毒的开发计算优化的广泛反应性抗原（COBRA）的现代方法利用当前的病毒监测信息来设计更广泛反应性的疫苗抗原。在这里，在小鼠中评估了 7 种新的重组血凝素（rHA）H3 COBRA 血凝素（HA）抗原。随后，基于它们诱导针对抗原漂移的 H3N2 病毒分离株的广泛反应性抗体的能力，选择了两个候选者 J4 和 NG2，用于在无流感预免疫动物中进行进一步测试。在无预免疫模型中，单价制剂的 J4 和 NG2 诱导了针对来自 2019 年的最近流行的 H3N2 流感病毒的广泛反应性抗体。单价制剂的 COBRA H1 和 H3 rHA 的二价混合物 Y2+J4 和 Y2+NG2 优于多种 WT H1+H3 单价 rHA 混合物，诱导了针对 2009 年至 2019 年的 H1N1 和 H3N2 分离株的血清保护性抗体。总的来说，新生成的 COBRA HA 抗原，即 Y2、J4 和 NG2，具有在无流感和预免疫动物中诱导单价和二价制剂中广泛反应性抗体的能力，并且通过诱导针对 2009 年至 2019 年的抗原漂移的历史 H1N1 和 H3N2 疫苗株的血清保护性抗体，这些抗原优于 H1 和 H3 WT rHA 疫苗抗原。标准护理流感病毒疫苗由来自不同流感病毒亚型的抗原混合物组成。首次在具有流感病毒预存免疫力的动物中研究了新型 COBRA H1 和 H3 HA 抗原，作为二价疫苗。COBRA HA 抗原鸡尾酒比针对 2009 年至 2019 年分离的 H1 和 H3 流感病毒的比较二价野生型 HA 疫苗诱导的更广泛反应性抗-HA 抗体。
