Broad cross neutralizing antibodies against sarbecoviruses generated by SARS-CoV-2 infection and vaccination in humans
Yabin Hu,
Qian Wu,
Fangfang Chang,
Jing Yang,
Xiaoyue Zhang,
Qijie Wang,
Jun Chen,
Shishan Teng,
Yongchen Liu,
Xingyu Zheng,
You Wang,
Rui Lu,
Dong Pan,
Zhanpeng Liu,
Fen Liu,
Tianyi Xie,
Chanfeng Wu,
Yinggen Tang,
Fei Tang,
Jun Qian,
Hongying Chen,
Wenpei Liu,
Yi-Ping Li,
Xiaowang Qu
Affiliations
Yabin Hu
College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases
Qian Wu
College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases
Fangfang Chang
Institute of Human Virology, Zhongshan School of Medicine, and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University
Jing Yang
The First School of Clinical Medicine, Southern Medical University
Xiaoyue Zhang
College of Life Sciences, Northwest A&F University
Qijie Wang
The Central Hospital of Shaoyang
Jun Chen
The First School of Clinical Medicine, Southern Medical University
Shishan Teng
College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases
Yongchen Liu
Institute of Human Virology, Zhongshan School of Medicine, and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University
Xingyu Zheng
College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases
You Wang
College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases
Rui Lu
College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases
Dong Pan
College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases
Zhanpeng Liu
College of Life Sciences, Northwest A&F University
Fen Liu
College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases
Tianyi Xie
College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases
Chanfeng Wu
College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases
Yinggen Tang
College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases
Fei Tang
Institute of Human Virology, Zhongshan School of Medicine, and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University
Jun Qian
Institute of Human Virology, Zhongshan School of Medicine, and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University
Hongying Chen
College of Life Sciences, Northwest A&F University
Wenpei Liu
College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases
Yi-Ping Li
Institute of Human Virology, Zhongshan School of Medicine, and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University
Xiaowang Qu
College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases
Abstract The outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2 highlight the need for countermeasures to prevent future coronavirus pandemics. Given the unpredictable nature of spillover events, preparing antibodies with broad coronavirus-neutralizing activity is an ideal proactive strategy. Here, we investigated whether SARS-CoV-2 infection and vaccination could provide cross-neutralizing antibodies (nAbs) against zoonotic sarbecoviruses. We evaluated the cross-neutralizing profiles of plasma and monoclonal antibodies constructed from B cells from coronavirus disease 2019 (COVID-19) convalescents and vaccine recipients; against sarbecoviruses originating from bats, civets, and pangolins; and against SARS-CoV-1 and SARS-CoV-2. We found that the majority of individuals with natural infection and vaccination elicited broad nAb responses to most tested sarbecoviruses, particularly to clade 1b viruses, but exhibited very low cross-neutralization to SARS-CoV-1 in both natural infection and vaccination, and vaccination boosters significantly augmented the magnitude and breadth of nAbs to sarbecoviruses. Of the nAbs, several exhibited neutralization activity against multiple sarbecoviruses by targeting the spike receptor-binding domain (RBD) and competing with angiotensin-converting enzyme 2 (ACE2) binding. SCM12-61 demonstrated exceptional potency, with half-maximal inhibitory concentration (IC50) values of 0.001–0.091 μg/mL against tested sarbecoviruses; while VSM9-12 exhibited remarkable cross-neutralizing breadth against sarbecoviruses and SARS-CoV-2 Omicron subvariants, highlighting the potential of these two nAbs in combating sarbecoviruses and SARS-CoV-2 Omicron subvariants. Collectively, our findings suggest that vaccination with an ancestral SARS-CoV-2 vaccine, in combination with broad nAbs against sarbecoviruses, may provide a countermeasure for preventing further sarbecovirus outbreaks in humans.
