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血凝素不稳定的 H3N2 疫苗参考病毒使抗原性发生偏倚，并阻止了雪貂之间的空气传播。

Hemagglutinin destabilization in H3N2 vaccine reference viruses skews antigenicity and prevents airborne transmission in ferrets.

机构信息

Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA.

St. Jude Children's Research Hospital Graduate School of Biomedical Sciences, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA.

出版信息

Sci Adv. 2023 Mar 29;9(13):eadf5182. doi: 10.1126/sciadv.adf5182.

DOI:10.1126/sciadv.adf5182
PMID:36989367
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10058244/
Abstract

During influenza virus entry, the hemagglutinin (HA) protein binds receptors and causes membrane fusion after endosomal acid activation. To improve vaccine efficiency and pandemic risk assessment for currently-dominant H3N2 influenza viruses, we investigated HA stability of 6 vaccine reference viruses and 42 circulating viruses. Recent vaccine reference viruses had destabilized HA proteins due to egg-adaptive mutation HA1-L194P. Virus growth in cell culture was independent of HA stability. In ferrets, the vaccine reference viruses and circulating viruses required a relatively stable HA (activation and inactivation pH < 5.5) for airborne transmissibility. The recent vaccine reference viruses with destabilized HA proteins had reduced infectivity, had no airborne transmissibility unless reversion to HA1-P194L occurred, and had skewed antigenicity away from the studied viruses and circulating H3N2 viruses. Other vaccine reference viruses with stabilized HAs retained infectivity, transmissibility, and antigenicity. Therefore, HA stabilization should be prioritized over destabilization in vaccine reference virus selection to reduce mismatches between vaccine and circulating viruses.

摘要

在流感病毒进入时，血凝素（HA）蛋白结合受体，在内涵体酸化激活后引起膜融合。为了提高目前占主导地位的 H3N2 流感病毒的疫苗效率和大流行风险评估，我们研究了 6 种疫苗参考病毒和 42 种循环病毒的 HA 稳定性。由于蛋适应突变 HA1-L194P，最近的疫苗参考病毒具有不稳定的 HA 蛋白。病毒在细胞培养中的生长不依赖于 HA 稳定性。在雪貂中，疫苗参考病毒和循环病毒需要相对稳定的 HA（激活和失活 pH < 5.5）才能进行空气传播。具有不稳定 HA 蛋白的最近的疫苗参考病毒具有降低的感染力，如果没有恢复到 HA1-P194L，则没有空气传播性，并且抗原性偏向于研究的病毒和循环的 H3N2 病毒。其他具有稳定 HA 的疫苗参考病毒保留了感染力、传染性和抗原性。因此，在疫苗参考病毒选择中，应该优先考虑 HA 稳定性而不是不稳定性，以减少疫苗和循环病毒之间的不匹配。

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