Chen Hui, Wang Junqiu, Liu Yunsong, Ling Ivy Quek Ee, Shih Chih Chuan, Wu Dafei, Fu Zhiyan, Lee Raphael Tze Chuen, Xu Miao, Chow Vincent T, Maurer-Stroh Sebastian, Zhou Da, Liu Jianjun, Zhai Weiwei
Human Genomics, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore.
Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Vaccines (Basel). 2022 Jun 6;10(6):907. doi: 10.3390/vaccines10060907.
Seasonal Influenza H3N2 virus poses a great threat to public health, but its vaccine efficacy remains suboptimal. One critical step in influenza vaccine production is the viral passage in embryonated eggs. Recently, the strength of egg passage adaptation was found to be rapidly increasing with time driven by convergent evolution at a set of functionally important codons in the hemagglutinin (HA1). In this study, we aim to take advantage of the negative correlation between egg passage adaptation and vaccine effectiveness (VE) and develop a computational tool for selecting the best candidate vaccine virus (CVV) for vaccine production. Using a probabilistic approach known as mutational mapping, we characterized the pattern of sequence evolution driven by egg passage adaptation and developed a new metric known as the adaptive distance (AD) which measures the overall strength of egg passage adaptation. We found that AD is negatively correlated with the influenza H3N2 vaccine effectiveness (VE) and ~75% of the variability in VE can be explained by AD. Based on these findings, we developed a computational package that can Measure the Adaptive Distance and predict vaccine Effectiveness (MADE). MADE provides a powerful tool for the community to calibrate the effect of egg passage adaptation and select more reliable strains with minimum egg-passaged changes as the seasonal A/H3N2 influenza vaccine.
季节性流感H3N2病毒对公众健康构成巨大威胁,但其疫苗效力仍不尽人意。流感疫苗生产中的一个关键步骤是在鸡胚中进行病毒传代。最近发现,在血凝素(HA1)一组功能重要的密码子处,由趋同进化驱动,随着时间推移,鸡胚传代适应性的强度迅速增加。在本研究中,我们旨在利用鸡胚传代适应性与疫苗效力(VE)之间的负相关关系,开发一种计算工具,用于为疫苗生产选择最佳候选疫苗病毒(CVV)。我们使用一种称为突变图谱的概率方法,表征了由鸡胚传代适应性驱动的序列进化模式,并开发了一种新的指标,称为适应性距离(AD),用于衡量鸡胚传代适应性的总体强度。我们发现AD与流感H3N2疫苗效力(VE)呈负相关,并且VE中约75%的变异性可以由AD解释。基于这些发现,我们开发了一个计算软件包,即测量适应性距离并预测疫苗效力(MADE)。MADE为业界提供了一个强大的工具,用于校准鸡胚传代适应性的影响,并选择作为季节性A/H3N2流感疫苗的、鸡胚传代变化最小的更可靠毒株。