BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection

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dc.contributor.authorCao, Yunlong
dc.contributor.authorYisimayi, Ayijiang
dc.contributor.authorJian, Fanchong
dc.contributor.authorSong, Weiliang
dc.contributor.authorXiao, Tianhe
dc.contributor.authorWang, Lei
dc.contributor.authorDu, Shuo
dc.contributor.authorWang, Jing
dc.contributor.authorLi, Qianqian
dc.contributor.authorChen, Xiaosu
dc.contributor.authorYu, Yuanling
dc.contributor.authorWang, Peng
dc.contributor.authorZhang, Zhiying
dc.contributor.authorLiu, Pulan
dc.contributor.authorAn, Ran
dc.contributor.authorHao, Xiaohua
dc.contributor.authorWang, Yao
dc.contributor.authorWang, Jing
dc.contributor.authorFeng, Rui
dc.contributor.authorSun, Haiyan
dc.contributor.authorZhao, Lijuan
dc.contributor.authorZhang, Wen
dc.contributor.authorZhao, Dong
dc.contributor.authorZheng, Jiang
dc.contributor.authorYu, Lingling
dc.contributor.authorLi, Can
dc.contributor.authorZhang, Na
dc.contributor.authorWang, Rui
dc.contributor.authorNiu, Xiao
dc.contributor.authorYang, Sijie
dc.contributor.authorSong, Xuetao
dc.contributor.authorChai, Yangyang
dc.contributor.authorHu, Ye
dc.contributor.authorShi, Yansong
dc.contributor.authorZheng, Linlin
dc.contributor.authorLi, Zhiqiang
dc.contributor.authorGu, Qingqing
dc.contributor.authorShao, Fei
dc.contributor.authorHuang, Weijin
dc.contributor.authorJin, Ronghua
dc.contributor.authorShen, Zhongyang
dc.contributor.authorWang, Youchun
dc.contributor.authorWang, Xiangxi
dc.contributor.authorXiao, Junyu
dc.contributor.authorXie, Xiaoliang Sunney
dc.date.accessioned2024-04-12T13:20:17Z
dc.date.available2024-04-12T13:20:17Z
dc.date.issued2022-06-17
dc.descriptionThe original publication is available at: https://www.nature.com
dc.description.abstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage1. The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA.2.12.1, BA.4 and BA.5 (BA.4 and BA.5 are hereafter referred collectively to as BA.4/BA.5) exhibit similar binding affinities to BA.2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA.2.12.1 and BA.4/BA.5 display increased evasion of neutralizing antibodies compared with BA.2 against plasma from triple-vaccinated individuals or from individuals who developed a BA.1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles2, epitope distribution3 and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA.1 infection. BA.1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA.1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1. Nevertheless, these neutralizing antibodies are largely evaded by BA.2 and BA.4/BA.5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab4 and cilgavimab5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.en_ZA
dc.description.urihttps://www.nature.com/articles/s41586-022-04980-y
dc.identifier.citationCao, Y., Yisimayi, A., Jian, F. et al. 2022. BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection. Nature 608:593–602. https://doi.org/10.1038/s41586-022-04980-y.en_ZA
dc.identifier.doihttps://doi.org/10.1038/s41586-022-04980-y
dc.identifier.issn0028-0836 (print)
dc.identifier.issn1476-4687 (online)
dc.identifier.orcidhttps://orcid.org/0000-0001-5918-1078
dc.identifier.orcidhttps://orcid.org/0000-0001-8703-3507
dc.identifier.orcidhttps://orcid.org/0000-0003-0936-0785
dc.identifier.orcidhttps://orcid.org/0000-0002-9084-9985
dc.identifier.orcidhttps://orcid.org/0000-0002-5690-9796
dc.identifier.orcidhttps://orcid.org/0000-0001-9281-5239
dc.identifier.orcidhttps://orcid.org/0000-0002-4246-8889
dc.identifier.orcidhttps://orcid.org/0000-0001-8496-172X
dc.identifier.orcidhttps://orcid.org/0000-0003-0045-4355
dc.identifier.orcidhttps://orcid.org/0000-0001-9769-5141
dc.identifier.orcidhttps://orcid.org/0000-0003-0635-278X
dc.identifier.orcidhttps://orcid.org/0000-0003-1822-1701
dc.identifier.urihttps://scholar.sun.ac.za/handle/10019.1/129627
dc.language.isoen_ZA
dc.publisherSpringer Nature
dc.rights.holderAuthors retain copyright
dc.titleBA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection
dc.typeArticle
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