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

Bin Ju (), Qing Fan, Miao Wang, Xuejiao Liao, Huimin Guo, Haiyan Wang, Xiangyang Ge, Lei Liu and Zheng Zhang ()
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Bin Ju: Shenzhen Third People’s Hospital
Qing Fan: Shenzhen Third People’s Hospital
Miao Wang: Shenzhen Third People’s Hospital
Xuejiao Liao: Shenzhen Third People’s Hospital
Huimin Guo: Shenzhen Third People’s Hospital
Haiyan Wang: Shenzhen Third People’s Hospital
Xiangyang Ge: Shenzhen Third People’s Hospital
Lei Liu: Shenzhen Third People’s Hospital
Zheng Zhang: Shenzhen Third People’s Hospital

Nature Communications, 2022, vol. 13, issue 1, 1-6

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-34400-8

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