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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

Author

Listed:
  • Bin Ju

    (Shenzhen Third People’s Hospital
    Southern University of Science and Technology
    Guangdong Key Laboratory for Anti-infection Drug Quality Evaluation)

  • Qing Fan

    (Shenzhen Third People’s Hospital
    Southern University of Science and Technology)

  • Miao Wang

    (Shenzhen Third People’s Hospital
    Southern University of Science and Technology)

  • Xuejiao Liao

    (Shenzhen Third People’s Hospital
    Southern University of Science and Technology)

  • Huimin Guo

    (Shenzhen Third People’s Hospital
    Southern University of Science and Technology)

  • Haiyan Wang

    (Shenzhen Third People’s Hospital
    Southern University of Science and Technology)

  • Xiangyang Ge

    (Shenzhen Third People’s Hospital
    Southern University of Science and Technology)

  • Lei Liu

    (Shenzhen Third People’s Hospital
    Southern University of Science and Technology)

  • Zheng Zhang

    (Shenzhen Third People’s Hospital
    Southern University of Science and Technology
    Guangdong Key Laboratory for Anti-infection Drug Quality Evaluation
    Shenzhen Research Center for Communicable Disease Diagnosis and Treatment of Chinese Academy of Medical Science)

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.

Suggested Citation

  • Bin Ju & Qing Fan & Miao Wang & Xuejiao Liao & Huimin Guo & Haiyan Wang & Xiangyang Ge & Lei Liu & Zheng Zhang, 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, Nature, vol. 13(1), pages 1-6, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34400-8
    DOI: 10.1038/s41467-022-34400-8
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    References listed on IDEAS

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    1. Qi Zhang & Bin Ju & Jiwan Ge & Jasper Fuk-Woo Chan & Lin Cheng & Ruoke Wang & Weijin Huang & Mengqi Fang & Peng Chen & Bing Zhou & Shuo Song & Sisi Shan & Baohua Yan & Senyan Zhang & Xiangyang Ge & Ji, 2021. "Potent and protective IGHV3-53/3-66 public antibodies and their shared escape mutant on the spike of SARS-CoV-2," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Bin Ju & Qi Zhang & Jiwan Ge & Ruoke Wang & Jing Sun & Xiangyang Ge & Jiazhen Yu & Sisi Shan & Bing Zhou & Shuo Song & Xian Tang & Jinfang Yu & Jun Lan & Jing Yuan & Haiyan Wang & Juanjuan Zhao & Shuy, 2020. "Human neutralizing antibodies elicited by SARS-CoV-2 infection," Nature, Nature, vol. 584(7819), pages 115-119, August.
    3. Sho Iketani & Lihong Liu & Yicheng Guo & Liyuan Liu & Jasper F.-W. Chan & Yiming Huang & Maple Wang & Yang Luo & Jian Yu & Hin Chu & Kenn K.-H. Chik & Terrence T.-T. Yuen & Michael T. Yin & Magdalena , 2022. "Antibody evasion properties of SARS-CoV-2 Omicron sublineages," Nature, Nature, vol. 604(7906), pages 553-556, April.
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    1. Laura Pérez-Alós & Cecilie Bo Hansen & Jose Juan Almagro Armenteros & Johannes Roth Madsen & Line Dam Heftdal & Rasmus Bo Hasselbalch & Mia Marie Pries-Heje & Rafael Bayarri-Olmos & Ida Jarlhelt & Seb, 2023. "Previous immunity shapes immune responses to SARS-CoV-2 booster vaccination and Omicron breakthrough infection risk," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Jernej Pušnik & Jasmin Zorn & Werner O. Monzon-Posadas & Kathrin Peters & Emmanuil Osypchuk & Sabine Blaschke & Hendrik Streeck, 2024. "Vaccination impairs de novo immune response to omicron breakthrough infection, a precondition for the original antigenic sin," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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