Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, United States of America.
Medigen, Inc., Frederick, Maryland, United States of America.
PLoS Pathog. 2022 Aug 25;18(8):e1010755. doi: 10.1371/journal.ppat.1010755. eCollection 2022 Aug.
Annual influenza vaccination is recommended to update the variable hemagglutinin antigens. Here, we first designed a virus-like particle (VLP) displaying consensus multi-neuraminidase (NA) subtypes (cN1, cN2, B cNA) and M2 ectodomain (M2e) tandem repeat (m-cNA-M2e VLP). Vaccination of mice with m-cNA-M2e VLP induced broad NA inhibition (NAI), and M2e antibodies as well as interferon-gamma secreting T cell responses. Mice vaccinated with m-cNA-M2e VLP were protected against influenza A (H1N1, H5N1, H3N2, H9N2, H7N9) and influenza B (Yamagata and Victoria lineage) viruses containing substantial antigenic variations. Protective immune contributors include cellular and humoral immunity as well as antibody-dependent cellular cytotoxicity. Furthermore, comparable cross protection by m-cNA-M2e VLP vaccination was induced in aged mice. This study supports a novel strategy of developing a universal vaccine against influenza A and B viruses potentially in both young and aged populations by inducing multi-NA subtype and M2e immunity with a single VLP entity.
每年接种流感疫苗是为了更新具有变异性的血凝素抗原。在这里，我们首次设计了一种展示共识多神经氨酸酶（NA）亚型（cN1、cN2、B cNA）和 M2 外显子（M2e）串联重复（m-cNA-M2e VLP）的病毒样颗粒（VLP）。用 m-cNA-M2e VLP 对小鼠进行疫苗接种可诱导广泛的神经氨酸酶抑制（NAI）、M2e 抗体以及干扰素-γ分泌的 T 细胞反应。用 m-cNA-M2e VLP 接种的小鼠可预防包含大量抗原变异的甲型流感（H1N1、H5N1、H3N2、H9N2、H7N9）和乙型流感（山形和维多利亚谱系）病毒。保护性免疫的贡献者包括细胞和体液免疫以及抗体依赖性细胞毒性。此外，m-cNA-M2e VLP 疫苗接种在老年小鼠中也能诱导出相当的交叉保护作用。这项研究支持了一种通过使用单个 VLP 实体诱导多 NA 亚型和 M2e 免疫来开发针对甲型和乙型流感病毒的通用疫苗的新策略，这种疫苗有可能在年轻和老年人群中使用。
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