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

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dc.contributor.authorCao, Yunlongen_ZA
dc.contributor.authorYisimayi, Ayijiangen_ZA
dc.contributor.authorJian, Fanchongen_ZA
dc.contributor.authorSong, Weiliangen_ZA
dc.contributor.authorXiao, Tianheen_ZA
dc.contributor.authorWang, Leien_ZA
dc.contributor.authorDu, Shuoen_ZA
dc.contributor.authorWang, Jingen_ZA
dc.contributor.authorLi, Qianqianen_ZA
dc.contributor.authorChen, Xiaosuen_ZA
dc.contributor.authorYu, Yuanlingen_ZA
dc.contributor.authorWang, Pengen_ZA
dc.contributor.authorZhang, Zhiyingen_ZA
dc.contributor.authorLiu, Pulanen_ZA
dc.contributor.authorAn, Ranen_ZA
dc.contributor.authorHao, Xiaohuaen_ZA
dc.contributor.authorWang, Yaoen_ZA
dc.contributor.authorWang, Jingen_ZA
dc.contributor.authorFeng, Ruien_ZA
dc.contributor.authorSun, Haiyanen_ZA
dc.contributor.authorZhao, Lijuanen_ZA
dc.contributor.authorZhang, Wenen_ZA
dc.contributor.authorZhao, Dongen_ZA
dc.contributor.authorZheng, Jiangen_ZA
dc.contributor.authorYu, Linglingen_ZA
dc.contributor.authorLi, Canen_ZA
dc.contributor.authorZhang, Naen_ZA
dc.contributor.authorWang, Ruien_ZA
dc.contributor.authorNiu, Xiaoen_ZA
dc.contributor.authorYang, Sijieen_ZA
dc.contributor.authorSong, Xuetaoen_ZA
dc.contributor.authorChai, Yangyangen_ZA
dc.contributor.authorHu, Yeen_ZA
dc.contributor.authorShi, Yansongen_ZA
dc.contributor.authorZheng, Linlinen_ZA
dc.contributor.authorLi, Zhiqiangen_ZA
dc.contributor.authorGu, Qingqingen_ZA
dc.contributor.authorShao, Feien_ZA
dc.contributor.authorHuang, Weijinen_ZA
dc.contributor.authorJin, Ronghuaen_ZA
dc.contributor.authorShen, Zhongyangen_ZA
dc.contributor.authorWang, Youchunen_ZA
dc.contributor.authorWang, Xiangxien_ZA
dc.contributor.authorXiao, Junyuen_ZA
dc.contributor.authorXie, Xiaoliang Sunneyen_ZA
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.format.extent29 pages : illustrations
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.subject.lcshSARS-CoV-2 variantsen_ZA
dc.subject.lcshCOVID-19 Vaccinesen_ZA
dc.subject.lcshCOVID-19 (Disease) -- Immunological aspectsen_ZA
dc.subject.lcshCOVID-19 (Disease) -- Vaccinationen_ZA
dc.subject.lcshCoronavirus infectionsen_ZA
dc.titleBA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infectionen_ZA
dc.typeArticleen_ZA
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