Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, USA.
Center for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFP, Health Canada, Ottawa, ON, Canada.
Virology. 2019 Sep;535:179-188. doi: 10.1016/j.virol.2019.07.008. Epub 2019 Jul 8.
Neuraminidase is the second major surface antigen on influenza virus. We investigated the immunogenicity and cross protective efficacy of virus-like particle containing neuraminidase derived from 2009 pandemic H1N1 influenza virus (N1 VLP) in comparison with inactivated split influenza vaccine. Immunization of mice with N1 VLP induced antibody responses specific for virus and cross-reactive neuraminidase inhibition activity whereas an inactivated split vaccine induced strain-specific hemagglutination inhibition activity. N1 VLP-immunized mice developed cross protective immunity against antigenically different influenza viruses, as determined by body weight changes, lung viral titers, infiltrating innate immune cells, and cytokines, and antibody secreting cells, and germinal center B cells. Also, N1 VLP-immune sera provided cross-protection in naïve mice. Immunity by N1 VLP vaccination was not compromised in Fc receptor γ-chain deficient mice. These results suggest that neuraminidase-presenting VLP can be developed as an effective cross-protective vaccine candidate along with current influenza vaccination.
神经氨酸酶是流感病毒的第二个主要表面抗原。我们研究了含有源自 2009 年大流行 H1N1 流感病毒的神经氨酸酶的病毒样颗粒(N1 VLP)与灭活的流感裂解疫苗相比的免疫原性和交叉保护功效。用 N1 VLP 免疫小鼠可诱导针对病毒和交叉反应性神经氨酸酶抑制活性的抗体反应,而灭活的流感裂解疫苗可诱导针对特定株的血凝抑制活性。N1 VLP 免疫的小鼠通过体重变化、肺部病毒滴度、浸润性先天免疫细胞和细胞因子以及抗体分泌细胞和生发中心 B 细胞的变化,针对抗原不同的流感病毒产生了交叉保护免疫力。此外,N1 VLP 免疫血清在新生小鼠中提供了交叉保护。N1 VLP 疫苗接种的免疫不受 Fc 受体 γ 链缺陷小鼠的影响。这些结果表明,神经氨酸酶呈递的 VLP 可以与当前的流感疫苗一起开发为有效的交叉保护疫苗候选物。