Longitudinal Analysis of Humoral and Cellular Immune Response up to 6 Months after SARS-CoV-2 BA.5/BF.7/XBB Breakthrough Infection and BA.5/BF.7-XBB Reinfection
Xun Wang,
Meng Zhang,
Kaifeng Wei,
Chen Li,
Jinghui Yang,
Shujun Jiang,
Chaoyue Zhao,
Xiaoyu Zhao,
Rui Qiao,
Yuchen Cui,
Yanjia Chen,
Jiayan Li,
Guonan Cai,
Changyi Liu,
Jizhen Yu,
Wenhong Zhang,
Faren Xie,
Pengfei Wang,
Yanliang Zhang
Affiliations
Xun Wang
Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200437, China
Meng Zhang
Department of Infectious Diseases, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210023, China
Kaifeng Wei
College of Traditional Chinese Medicine·College of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
Chen Li
Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200437, China
Jinghui Yang
Department of Infectious Diseases, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210023, China
Shujun Jiang
Department of Infectious Diseases, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210023, China
Chaoyue Zhao
Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200437, China
Xiaoyu Zhao
Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200437, China
Rui Qiao
Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200437, China
Yuchen Cui
Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200437, China
Yanjia Chen
Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200437, China
Jiayan Li
Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200437, China
Guonan Cai
Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200437, China
Changyi Liu
Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200437, China
Jizhen Yu
Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200437, China
Wenhong Zhang
Department of Infectious Diseases, National Medical Center for Infectious Diseases and Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200437, China
Faren Xie
Department of Infectious Diseases, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210023, China
Pengfei Wang
Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetic Engineering, MOE Engineering Research Center of Gene Technology, School of Life Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200437, China
Yanliang Zhang
Department of Infectious Diseases, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210023, China
The rapid mutation of SARS-CoV-2 has led to multiple rounds of large-scale breakthrough infection and reinfection worldwide. However, the dynamic changes of humoral and cellular immunity responses to several subvariants after infection remain unclear. In our study, a 6-month longitudinal immune response evaluation was conducted on 118 sera and 50 PBMC samples from 49 healthy individuals who experienced BA.5/BF.7/XBB breakthrough infection or BA.5/BF.7-XBB reinfection. By studying antibody response, memory B cell, and IFN-γ secreting CD4+/CD8+ T cell response to several SARS-CoV-2 variants, we observed that each component of immune response exhibited distinct kinetics. Either BA.5/BF.7/XBB breakthrough infection or BA.5/BF.7-XBB reinfection induces relatively high level of binding and neutralizing antibody titers against Omicron subvariants at an early time point, which rapidly decreases over time. Most of the individuals at 6 months post-breakthrough infection completely lost their neutralizing activities against BQ.1.1, CH.1.1, BA.2.86, JN.1 and XBB subvariants. Individuals with BA.5/BF.7-XBB reinfection exhibit immune imprinting shifting and recall pre-existing BA.5/BF.7 neutralization antibodies. In the BA.5 breakthrough infection group, the frequency of BA.5 and XBB.1.16-RBD specific memory B cells, resting memory B cells, and intermediate memory B cells gradually increased over time. On the other hand, the frequency of IFN-γ secreting CD4+/CD8+ T cells induced by WT/BA.5/XBB.1.16 spike trimer remains stable over time. Overall, our research indicates that individuals with breakthrough infection have rapidly declining antibody levels but have a relatively stable cellular immunity that can provide some degree of protection from future exposure to new antigens.
