Center for Vaccines and Immunology, University of Georgia, Athens, GA, USA.
Department of Infectious Diseases, University of Georgia, Athens, GA, USA.
Hum Vaccin Immunother. 2024 Dec 31;20(1):2403175. doi: 10.1080/21645515.2024.2403175. Epub 2024 Sep 18.
Influenza neuraminidase (NA) is a promising target for a broadly protective vaccine. In this study, the Computationally Optimized Broadly Reactive Antigen (COBRA) methodology was used to develop N2 NA vaccine candidates. The unique wild type (WT) N2 sequences of human and swine influenza strains isolated between 1957 and 2019 were used to design the COBRA N2-A NA vaccine, while the unique WT N2 sequences of human influenza strains isolated between 2000 and 2019 were used to design the COBRA N2-B NA vaccine. Sera collected from COBRA N2 NA vaccinated mice showed more broadly reactive antibody responses against a broad panel of H×N2 influenza virus strains than sera collected from mice vaccinated with WT N2 NA vaccines. Antibodies elicited by COBRA or WT N2 NA antigens cross react with recent human H3N2 influenza viruses from different clades, while the antibodies elicited by A/Switzerland/9715293/2013 hemagglutinin (HA) reacted with viruses from the same clade. Furthermore, mice vaccinated with COBRA N2-B NA vaccine had lower viral lung titers compared to mock vaccinated mice when challenged with human H3N2 influenza viruses. Thus, the COBRA N2 NA vaccines elicit broadly protective murine anti-NA antibodies against multiple strains across subtypes and the viral loads were significantly decreased in the lungs of the mice in the COBRA N2 NA vaccine groups, compared to the mice in the mock vaccinated group, indicating that the COBRA-based N2 subtype NA vaccines have a potential to be a component in a universal influenza vaccine.
流感神经氨酸酶（NA）是一种有前途的广谱保护疫苗靶点。在这项研究中，使用计算优化的广泛反应性抗原（COBRA）方法来开发 N2 NA 疫苗候选物。使用 1957 年至 2019 年之间分离的人类和猪流感株的独特野生型（WT）N2 序列来设计 COBRA N2-A NA 疫苗，而使用 2000 年至 2019 年之间分离的人类流感株的独特 WT N2 序列来设计 COBRA N2-B NA 疫苗。从 COBRA N2 NA 疫苗接种的小鼠中收集的血清显示出对广泛的 H×N2 流感病毒株更广泛的反应性抗体反应，而从接种 WT N2 NA 疫苗的小鼠中收集的血清则显示出更广泛的反应性抗体反应。COBRA 或 WT N2 NA 抗原引发的抗体与来自不同谱系的最近的人类 H3N2 流感病毒交叉反应，而 A/Switzerland/9715293/2013 血凝素（HA）引发的抗体与来自同一谱系的病毒反应。此外，当用人类 H3N2 流感病毒攻毒时，与 mock 接种的小鼠相比，接种 COBRA N2-B NA 疫苗的小鼠的肺部病毒滴度更低。因此，COBRA N2 NA 疫苗在多种亚型的多种株系中引发了广泛的保护性鼠抗 NA 抗体，与 mock 接种组的小鼠相比，COBRA N2 NA 疫苗组的小鼠肺部病毒载量显著降低，这表明基于 COBRA 的 N2 亚型 NA 疫苗有可能成为通用流感疫苗的一个组成部分。
