Radiation Research Division, Korea Atomic Energy Research Institute , Jeongeup, Republic of Korea.
Department of Radiation Biotechnology and Applied Radioisotope Science, University of Science and Technology , Daejeon, Republic of Korea.
Hum Vaccin Immunother. 2021 Feb 1;17(2):485-496. doi: 10.1080/21645515.2020.1780091. Epub 2020 Jul 9.
The most widely used influenza vaccines are prepared by chemical inactivation. However, chemical, especially formalin, treatment-induced modifications of the antigenic structure of the virus are frequently associated with adverse effects including low efficacy of protection, unexpected immune responses, or exacerbation of disease. Gamma-irradiation was suggested as an alternative influenza virus inactivation method due to its great features of completely inactivating virus while not damaging the structures of protein antigens, and cross-protective ability against heterologous strains. However, immunological features of gamma radiation-inactivated influenza vaccine have not been fully understood. In this study, we aimed to investigate the humoral and cellular immune responses of gamma radiation-inactivated influenza vaccine. The gamma irradiation-inactivated influenza vaccine (RADVAX) showed complete viral inactivation but retained normal viral structure with functional activities of viral protein antigens. Intranasal immunization of RADVAX provided better protection against influenza virus infection than formalin-inactivated influenza virus (FIV) in mice. RADVAX greatly enhanced the production of virus-specific serum IgG and alveolar mucosal IgA, which effectively neutralized HA (hemagglutinin) and NA (neuraminidase) activities, and blocked viral binding to the cells, respectively. Further analysis of IgG subclasses showed RADVAX-immunized sera had higher levels of IgG1 and IgG2a than those of FIV-immunized sera. In addition, analysis of cellular immunity found RADVAX induced strong dendritic cells (DC) activation resulting in higher DC-mediated activation of CD8 T cells than FIV. The results support improved immunogenicity by RADVAX.
最广泛使用的流感疫苗是通过化学失活制备的。然而，化学处理，特别是甲醛处理，会导致病毒抗原结构发生修饰，这常常与不良反应相关，包括保护效果低、意外的免疫反应或疾病恶化。伽马射线辐照被认为是一种替代流感病毒灭活方法，因为它具有完全灭活病毒而不破坏蛋白抗原结构的巨大特性，并且具有针对异源株的交叉保护能力。然而，伽马射线灭活流感疫苗的免疫学特征尚未得到充分理解。在这项研究中，我们旨在研究伽马射线灭活流感疫苗的体液和细胞免疫反应。伽马射线灭活流感疫苗（RADVAX）显示出完全的病毒失活，但保留了正常的病毒结构和病毒蛋白抗原的功能活性。鼻内免疫 RADVAX 比甲醛灭活流感病毒（FIV）更能有效保护小鼠免受流感病毒感染。RADVAX 大大增强了病毒特异性血清 IgG 和肺泡粘膜 IgA 的产生，分别有效地中和了 HA（血凝素）和 NA（神经氨酸酶）的活性，并阻断了病毒与细胞的结合。对 IgG 亚类的进一步分析表明，RADVAX 免疫血清中的 IgG1 和 IgG2a 水平高于 FIV 免疫血清。此外，细胞免疫分析发现，RADVAX 诱导了强烈的树突状细胞（DC）激活，导致 DC 介导的 CD8 T 细胞激活水平高于 FIV。结果支持了 RADVAX 提高的免疫原性。
