A human coronavirus evolves antigenically to escape antibody immunity.

A human coronavirus evolves antigenically to escape antibody immunity.
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DOI:
10.1371/journal.ppat.1009453
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发表时间:
2021-04
期刊:
影响因子:
6.7
通讯作者:
Bloom JD
Bloom JD
中科院分区:
医学1区
文献类型:
--
作者:
Eguia RT;Crawford KHD;Stevens-Ayers T;Kelnhofer-Millevolte L;Greninger AL;Englund JA;Boeckh MJ;Bloom JD

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对冠状病毒的抗体免疫有着浓厚的兴趣。然而,目前尚不清楚冠状病毒是否进化以逃避这种免疫,如果是的话,速度有多快。在这里,我们通过描述人类冠状病毒229E的历史演变来解决这个问题。我们鉴定了20世纪80年代和90年代的人血清,这些血清对同时期的229E具有中和效价,与SARS-CoV-2感染或疫苗接种诱导的抗SARS-CoV-2效价相当。我们将这些血清与收集血清后分离的229E株进行测试,发现这些血清中和效价较低,对这些“未来”的病毒。在某些情况下,中和滴度为1:100的同时期229E病毒株的血清不能检测到中和8-17年后分离的病毒株。“未来”病毒的中和力下降是由于病毒尖峰的抗原性进化,特别是在受体结合区域。如果这些结果外推到其他冠状病毒,那么定期更新SARS-CoV-2疫苗可能是明智的。控制SARS-CoV-2病毒的希望依赖于疫苗接种或感染来产生免疫力,以防止后续感染。然而,“普通感冒”的季节性冠状病毒每隔几年就会再次感染一次人。目前尚不清楚这些再次感染是因为免疫力迅速下降,还是因为病毒进化以逃避先前感染引发的免疫力。在这里,我们在普通感冒冠状病毒229E的背景下研究第二个假设。我们测试了旧人类血清中的抗体对同时代的旧229E病毒和收集血清后进化的较新病毒的中和效果。我们发现,随着229E的进化,其尖峰蛋白会积累突变,从而逃避老年人类血清的中和。病毒进化降低免疫力的速度因人而异,但在某些情况下,不到十年的进化足以完全消除人类血清对同时期病毒的有效中和。许多病毒突变发生在新出现的SARS-CoV-2变种中正在发生变化的尖峰区域(RBD和NTD)。因此,我们的结果表明,冠状病毒疫苗可能需要定期更新,以跟上病毒进化的步伐。
There is intense interest in antibody immunity to coronaviruses. However, it is unknown if coronaviruses evolve to escape such immunity, and if so, how rapidly. Here we address this question by characterizing the historical evolution of human coronavirus 229E. We identify human sera from the 1980s and 1990s that have neutralizing titers against contemporaneous 229E that are comparable to the anti-SARS-CoV-2 titers induced by SARS-CoV-2 infection or vaccination. We test these sera against 229E strains isolated after sera collection, and find that neutralizing titers are lower against these “future” viruses. In some cases, sera that neutralize contemporaneous 229E viral strains with titers >1:100 do not detectably neutralize strains isolated 8–17 years later. The decreased neutralization of “future” viruses is due to antigenic evolution of the viral spike, especially in the receptor-binding domain. If these results extrapolate to other coronaviruses, then it may be advisable to periodically update SARS-CoV-2 vaccines. Hopes for controlling SARS-CoV-2 rely on vaccination or infection to confer immunity that protects against subsequent infection. However, the “common-cold” seasonal coronaviruses re-infect people every few years. It has been unclear if these re-infections occur because immunity wanes rapidly, or because the virus evolves to escape immunity elicited by prior infection. Here we investigate the second hypothesis in the context of the common-cold coronavirus 229E. We test how well antibodies in old human sera neutralize both contemporaneous old 229E viruses, and more recent viruses that evolved after the sera was collected. We find that as 229E evolves, its spike protein accumulates mutations that escape neutralization by older human sera. The rate at which viral evolution degrades immunity varies among individuals, but in some cases less than a decade of evolution is sufficient to completely eliminate neutralization by human sera that is potent against contemporaneous viruses. Many of the viral mutations occur in the same regions of the spike (the RBD and NTD) that are changing in emerging variants of SARS-CoV-2. Therefore, our results suggest that coronavirus vaccines may need to be periodically updated to keep pace with viral evolution.
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期刊: Nature
影响因子: 64.8
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期刊: Journal of immunology (Baltimore, Md. : 1950)
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影响因子: 9.4
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期刊: JCI INSIGHT
影响因子: 8
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期刊: Science (New York, N.Y.)
影响因子: --
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