Dynamics of Crossed Acquired Immunity Against SARS‐CoV‐2 Variants: From Vaccine to Hybrid Immunity in China
The immune response to evolving Omicron variants in China, especially after booster doses and breakthrough infections post-Zero-COVID-19 policy, is poorly understood. In a 14-month cohort of 206 adults, baseline assessments were conducted the day before the third COVID-19 vaccine dose (Visit 1), with follow-ups at 1 (Visit 2), 3 (Visit 3), 6 (Visit 4), 9 (Visit 5), and 14 (Visit 6) months after the dose. The lifting of Zero-COVID-19 policy coincided with a surge in Omicron breakthrough infections among our participants, occurring 12 months after the third vaccine dose. We assessed neutralizing antibodies (NAbs) against prototype/variant strains and T cell responses to BA.5 Spike and conserved peptide pools (CPPs) in PBMCs. NAbs and T-cell responses significantly increased after policy's cessation, surpassing levels seen 1 month post-third dose. Over 90% of participants showed notable NAb increases between Visit 5 and 6 without additional boosters, suggesting probable SARS-CoV-2 infections. Cross-reactive NAbs decreased for BA.5 (1.5-fold), XBB.1.5 (15.4-fold), and JN.1 (44.8-fold) compared to the prototype strain. T-cell responses to BA.5 Spike and CPPs remained stable. From vaccine to hybrid immunity, sustained cellular immunity protects against severe outcomes despite reduced NAb cross-reactivity. Updated variant-targeted vaccines remain crucial, especially for those with weaker immune responses.
Authors
- Qinlin Chen
- Hao Cai (ORCID: https://orcid.org/0000-0002-1492-4701)
- Pinpin Long (ORCID: https://orcid.org/0000-0002-4435-7111)
- Yingying Zhao (ORCID: https://orcid.org/0000-0002-0213-3291)
- Siyuan Peng (ORCID: https://orcid.org/0000-0002-7465-239X)
- Jinfeng Lei
- Jia Li (ORCID: https://orcid.org/0000-0003-0522-0873)
- Xuemei Song
- Chaolong Wang (ORCID: https://orcid.org/0000-0003-3945-1012)
- Yuying Wen
- Xinlian Li (ORCID: https://orcid.org/0000-0002-1666-6953)
- Shanshan Cheng (ORCID: https://orcid.org/0000-0002-3020-6195)
- Tingting Yuan (ORCID: https://orcid.org/0009-0005-2498-8193)
- Jun Xu (ORCID: https://orcid.org/0000-0001-9285-158X)
- Dongsheng Di (ORCID: https://orcid.org/0000-0002-3663-4035)
- Zhangbo Cui (ORCID: https://orcid.org/0009-0000-1501-0402)
- Shuo Feng (ORCID: https://orcid.org/0000-0002-6683-162X)
- Jinge Cao
- Mengze Gan (ORCID: https://orcid.org/0000-0002-9663-6737)
- Xionglin Fan (ORCID: https://orcid.org/0000-0001-9754-372X)
- Qian Liu (ORCID: https://orcid.org/0000-0001-5128-2413)
- Qi Wang (ORCID: https://orcid.org/0000-0002-1728-8763)
- Zhihao Zhang (ORCID: https://orcid.org/0000-0002-3260-7195)
- Meilin Liu (ORCID: https://orcid.org/0000-0002-6188-2372)
- Yaxin Wang (ORCID: https://orcid.org/0000-0003-0695-3542)
- Li Liu (ORCID: https://orcid.org/0000-0001-7455-1735)
- Zhen Wang (ORCID: https://orcid.org/0000-0003-3173-6961)
- Hao Wang (ORCID: https://orcid.org/0000-0003-4493-3147)
- Shui Liu (ORCID: https://orcid.org/0000-0002-0765-2867)
- Bihao Wu
- Tingting Zhou (ORCID: https://orcid.org/0000-0003-1331-3981)
- Xiaoyu Kang (ORCID: https://orcid.org/0000-0002-6331-0722)
- Guoliang Yang
- Rui Gong (ORCID: https://orcid.org/0000-0001-9222-5642)
- Yu Yuan
- Tangchun Wu (ORCID: https://orcid.org/0000-0001-9931-5106)
- Jing Yi
Institutions
- Chinese Academy of Sciences (CN)
- University of Oxford (GB)
- Hubei Provincial Center for Disease Control and Prevention (CN)
- Wuhan Institute of Virology (CN)
- Central Hospital of Wuhan (CN)
- Huazhong University of Science and Technology (CN)
Publication Details
- Journal
- Journal of Medical Virology
- Published
- 2025-07-01
- DOI
- https://doi.org/10.1002/jmv.70487
- Citations
- 2
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 2.79
Funders
- National Natural Science Foundation of China
- Huazhong University of Science and Technology
- Tongji University
- National Key Research and Development Program of China
- Tongji Medical College, Huazhong University of Science and Technology