Antigenic sin of wild-type SARS-CoV-2 vaccine shapes poor cross-neutralization of BA.4/5/2.75 subvariants in BA.2 breakthrough infections

Ju，Bin1,2,3; Fan，Qing1,2; Wang，Miao1,2; Liao，Xuejiao1,2; Guo，Huimin1,2; Wang，Haiyan1,2; Ge，Xiangyang1,2; Liu，Lei1,2; Zhang，Zheng1,2,3,4

2022-12-01

10.1038/s41467-022-34400-8

Nature Communications   影响因子和分区

2041-1723

With declining SARS-CoV-2-specific antibody titers and increasing numbers of spike mutations, the ongoing emergence of Omicron subvariants causes serious challenges to current vaccination strategies. BA.2 breakthrough infections have occurred in people who have received the wild-type vaccines, including mRNA, inactivated, or recombinant protein vaccines. Here, we evaluate the antibody evasion of recently emerged subvariants BA.4/5 and BA.2.75 in two inactivated vaccine-immunized cohorts with BA.2 breakthrough infections. Compared with the neutralizing antibody titers against BA.2, marked reductions are observed against BA.2.75 in both 2-dose and 3-dose vaccine groups. In addition, although BA.2 breakthrough infections induce a certain cross-neutralization capacity against later Omicron subvariants, the original antigenic sin phenomenon largely limits the improvement of variant-specific antibody response. These findings suggest that BA.2 breakthrough infections seem unable to provide sufficient antibody protection against later subvariants such as BA.2.75 in the current immunization background with wild-type vaccines.

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通讯

National Science Fund for Distinguished Young Scholars[82025022] ; National Natural Science Foundation of China["92169204","82002140","82171752"] ; China Postdoctoral Science Foundation[2021M703445] ; Guangdong Basic and Applied Basic Research Foundation["2021B1515020034","2019A1515011197"] ; Shenzhen Science and Technology Program["RCYX20200714114700046","RCBS20210706092345028"] ; Science and Technology Innovation Committee of Shenzhen Municipality["JSGG20220226085550001","JSGG20200207155251653","JSGG20200807171401008","JSGG20210901145200002"] ; Shenzhen Natural Science Foundation["JCYJ20190809115617365","JCYJ20200109144201725"]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000886221900012

NATURE PORTFOLIO

2-s2.0-85142293505

Scopus

1.Institute for Hepatology,National Clinical Research Center for Infectious Disease,Shenzhen Third People’s Hospital,Shenzhen,Guangdong Province,518112,China
2.The Second Affiliated Hospital,School of Medicine,Southern University of Science and Technology,Shenzhen,Guangdong Province,518112,China
3.Guangdong Key Laboratory for Anti-infection Drug Quality Evaluation,Shenzhen,Guangdong Province,518112,China
4.Shenzhen Research Center for Communicable Disease Diagnosis and Treatment of Chinese Academy of Medical Science,Shenzhen,Guangdong Province,518112,China

Ju，Bin,Fan，Qing,Wang，Miao,et al. Antigenic sin of wild-type SARS-CoV-2 vaccine shapes poor cross-neutralization of BA.4/5/2.75 subvariants in BA.2 breakthrough infections[J]. Nature Communications,2022,13(1).

Ju，Bin.,Fan，Qing.,Wang，Miao.,Liao，Xuejiao.,Guo，Huimin.,...&Zhang，Zheng.(2022).Antigenic sin of wild-type SARS-CoV-2 vaccine shapes poor cross-neutralization of BA.4/5/2.75 subvariants in BA.2 breakthrough infections.Nature Communications,13(1).

Ju，Bin,et al."Antigenic sin of wild-type SARS-CoV-2 vaccine shapes poor cross-neutralization of BA.4/5/2.75 subvariants in BA.2 breakthrough infections".Nature Communications 13.1(2022).