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J Med Virol . Dynamics of Crossed Acquired Immunity Against SARS-CoV-2 Variants: From Vaccine to Hybrid Immunity in China

tetano

Editor, Senior Moderator
J Med Virol


. 2025 Jul;97(7):e70487.
doi: 10.1002/jmv.70487. Dynamics of Crossed Acquired Immunity Against SARS-CoV-2 Variants: From Vaccine to Hybrid Immunity in China

Hao Wang[SUP] 1 [/SUP], Zhihao Zhang[SUP] 1 [/SUP], Mengze Gan[SUP] 2 [/SUP], Zhangbo Cui[SUP] 1 [/SUP], Bihao Wu[SUP] 3 [/SUP], Shuo Feng[SUP] 4 [/SUP], Jun Xu[SUP] 5 [/SUP], Jinge Cao[SUP] 2 [/SUP], Yuying Wen[SUP] 1 [/SUP], Zhen Wang[SUP] 1 [/SUP], Jia Li[SUP] 1 [/SUP], Dongsheng Di[SUP] 1 [/SUP], Siyuan Peng[SUP] 5 [/SUP], Jinfeng Lei[SUP] 5 [/SUP], Guoliang Yang[SUP] 6 [/SUP], Yingying Zhao[SUP] 1 [/SUP], Xuemei Song[SUP] 1 [/SUP], Xiaoyu Kang[SUP] 1 [/SUP], Meige Liu[SUP] 1 [/SUP], Yaxin Wang[SUP] 1 [/SUP], Tingting Yuan[SUP] 1 [/SUP], Tingting Zhou[SUP] 1 [/SUP], Shui Liu[SUP] 1 [/SUP], Qian Liu[SUP] 1 [/SUP], Jing Yi[SUP] 1 [/SUP], Xinlian Li[SUP] 1 [/SUP], Hao Cai[SUP] 1 [/SUP], Qinlin Chen[SUP] 1 [/SUP], Pinpin Long[SUP] 1 [/SUP], Yu Yuan[SUP] 1 [/SUP], Shanshan Cheng[SUP] 1 [/SUP], Chaolong Wang[SUP] 1 [/SUP], Rui Gong[SUP] 3 [/SUP], Qi Wang[SUP] 1 [/SUP], Xionglin Fan[SUP] 2 [/SUP], Tangchun Wu[SUP] 1 [/SUP], Li Liu[SUP] 1 [/SUP]



Affiliations
Abstract

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.

Keywords: SARS‐CoV‐2 variants; crossed acquired immunity; dynamics; hybrid immunity; vaccine immunity.

 
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