Vasilev Kirill, Hoxie Irene, Puente-Massaguer Eduard, Yueh Joshua, Bhavsar Disha, Singh Maya, Mallett Corey P, Zimmermann Joseph, Krammer Florian
Department of Microbiology, Icahn School of Medicine at Mount Sinai (ISMMS), New York, NY, 10029, USA.
GSK, Rockville, MD, USA.
NPJ Vaccines. 2025 Jul 10;10(1):149. doi: 10.1038/s41541-025-01209-7.
Development of mucosal influenza virus vaccines which protect the site of viral entry is of high importance. Recombinant neuraminidase (NA) has emerged as an antigenically conserved intranasal vaccine candidate, capable of inducing broad cross-protection, but it requires effective mucosal adjuvants. Here, we analyze the immunogenicity and protective efficacy of a mucosal recombinant NA-based influenza virus vaccine adjuvanted with the outer membrane proteins from Neisseria meningitidis complexed with exogenous lipopolysaccharides (LPS) from Shigella flexneri or endogenous LPS from N. meningitidis. We observed increased follicular T-helper and germinal center B-cell population percentages in nasal-associated lymphoid tissue, enhanced IgA and IgG antibody responses, and accumulation of lung-resident memory T cells. The vaccine provided complete protection against homologous and partial protection against a heterologous influenza virus (clade 2.3.4.4b H5N1) challenge. These findings underscore the potential of bacterial membrane-derived adjuvants for developing robust mucosal influenza vaccines.
开发能够保护病毒进入部位的黏膜流感病毒疫苗至关重要。重组神经氨酸酶（NA）已成为一种抗原保守的鼻内疫苗候选物，能够诱导广泛的交叉保护，但它需要有效的黏膜佐剂。在此，我们分析了一种基于黏膜重组NA的流感病毒疫苗的免疫原性和保护效果，该疫苗用来自脑膜炎奈瑟菌的外膜蛋白与来自福氏志贺菌的外源性脂多糖（LPS）或来自脑膜炎奈瑟菌的内源性LPS复合作为佐剂。我们观察到鼻相关淋巴组织中滤泡辅助性T细胞和生发中心B细胞群体百分比增加，IgA和IgG抗体反应增强，以及肺驻留记忆T细胞的积累。该疫苗对同源流感病毒攻击提供了完全保护，对异源流感病毒（2.3.4.4b H5N1分支）攻击提供了部分保护。这些发现强调了细菌膜衍生佐剂在开发强大的黏膜流感疫苗方面的潜力。
