Research Centre for Infectious Diseases, Department of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, SA, Australia.
Gamma Vaccines Pty Ltd, Yarralumla, ACT, Australia.
Front Immunol. 2021 Nov 24;12:761632. doi: 10.3389/fimmu.2021.761632. eCollection 2021.
Influenza A virus presents a constant pandemic threat due to the mutagenic nature of the virus and the inadequacy of current vaccines to protect against emerging strains. We have developed a whole-inactivated influenza vaccine using γ-irradiation (γ-Flu) that can protect against both vaccine-included strains as well as emerging pandemic strains. γ-irradiation is a widely used inactivation method and several γ-irradiated vaccines are currently in clinical or pre-clinical testing. To enhance vaccine efficacy, irradiation conditions should be carefully considered, particularly irradiation temperature. Specifically, while more damage to virus structure is expected when using higher irradiation temperatures, reduced radiation doses will be required to achieve sterility. In this study, we compared immunogenicity of γ-Flu irradiated at room temperature, chilled on ice or frozen on dry ice using different doses of γ-irradiation to meet internationally accepted sterility assurance levels. We found that, when irradiating at sterilising doses, the structural integrity and vaccine efficacy were well maintained in all preparations regardless of irradiation temperature. In fact, using a higher temperature and lower radiation dose appeared to induce higher neutralising antibody responses and more effective cytotoxic T cell responses. This outcome is expected to simplify irradiation protocols for manufacturing of highly effective irradiated vaccines.
甲型流感病毒由于其病毒的突变性质和当前疫苗无法有效预防新兴毒株，因此一直构成着不断的大流行威胁。我们已经开发了一种使用γ-射线（γ-Flu）的全灭活流感疫苗，该疫苗可以预防包括疫苗株在内的新兴大流行株。γ-射线辐照是一种广泛使用的灭活方法，目前有几种γ-射线辐照疫苗正在临床或临床前研究中。为了提高疫苗的效力，应仔细考虑辐照条件，特别是辐照温度。具体而言，虽然使用较高的辐照温度预计会对病毒结构造成更大的损害，但为了达到无菌状态，所需的辐射剂量将会减少。在这项研究中，我们比较了使用不同剂量的γ-射线在室温、冰上冷却或干冰上冷冻辐照的γ-Flu 的免疫原性，以达到国际公认的无菌保证水平。我们发现，在进行杀菌剂量的辐照时，所有制剂的结构完整性和疫苗效力都得到了很好的维持，无论辐照温度如何。事实上，使用较高的温度和较低的辐射剂量似乎会引起更高的中和抗体反应和更有效的细胞毒性 T 细胞反应。这一结果有望简化用于制造高效灭活疫苗的辐照方案。
