Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
PLoS Pathog. 2021 Apr 19;17(4):e1009171. doi: 10.1371/journal.ppat.1009171. eCollection 2021 Apr.
Virions are a common antigen source for many viral vaccines. One limitation to using virions is that the antigen abundance is determined by the content of each protein in the virus. This caveat especially applies to viral-based influenza vaccines where the low abundance of the neuraminidase (NA) surface antigen remains a bottleneck for improving the NA antibody response. Our systematic analysis using recent H1N1 vaccine antigens demonstrates that the NA to hemagglutinin (HA) ratio in virions can be improved by exchanging the viral backbone internal genes, especially the segment encoding the polymerase PB1 subunit. The purified inactivated virions with higher NA content show a more spherical morphology, a shift in the balance between the HA receptor binding and NA receptor release functions, and induce a better NA inhibitory antibody response in mice. These results indicate that influenza viruses support a range of ratios for a given NA and HA pair which can be used to produce viral-based influenza vaccines with higher NA content that can elicit more balanced neutralizing antibody responses to NA and HA.
病毒粒子是许多病毒疫苗的常见抗原来源。使用病毒粒子的一个限制是，抗原的丰度取决于病毒中每种蛋白质的含量。对于基于病毒的流感疫苗来说，这一点尤其适用，因为神经氨酸酶 (NA) 表面抗原的低丰度仍然是提高 NA 抗体反应的瓶颈。我们使用最近的 H1N1 疫苗抗原进行的系统分析表明，通过交换病毒内部基因（尤其是编码聚合酶 PB1 亚基的基因），可以提高病毒粒子中 NA 与血凝素 (HA) 的比例。具有更高 NA 含量的纯化灭活病毒粒子显示出更球形的形态，HA 受体结合与 NA 受体释放功能之间的平衡发生转变，并且在小鼠中诱导更好的 NA 抑制性抗体反应。这些结果表明，流感病毒支持给定的 NA 和 HA 对的一系列比例，可用于生产具有更高 NA 含量的基于病毒的流感疫苗，从而引发对 NA 和 HA 的更平衡的中和抗体反应。
