Broad cross neutralizing antibodies against sarbecoviruses generated by SARS-CoV-2 infection and vaccination in humans
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 (IC<sub>50</sub>) 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.
Authors
- Zhanpeng Liu (ORCID: https://orcid.org/0000-0001-8865-8808)
- Tianyi Xie (ORCID: https://orcid.org/0000-0001-6390-6043)
- Jun Qian (ORCID: https://orcid.org/0000-0001-7697-2875)
- Wenpei Liu (ORCID: https://orcid.org/0000-0002-4624-2879)
- Fangfang Chang
- Qijie Wang (ORCID: https://orcid.org/0000-0002-9910-1455)
- Fei Tang (ORCID: https://orcid.org/0000-0003-1475-5028)
- Shishan Teng
- Xiaowang Qu
- Yi‐Ping Li (ORCID: https://orcid.org/0000-0001-6011-3101)
- H. J. Yang (ORCID: https://orcid.org/0009-0004-8274-9863)
- You Wang (ORCID: https://orcid.org/0000-0002-1725-7465)
- Xiaoyue Zhang (ORCID: https://orcid.org/0000-0002-9381-8930)
- Rui Lü (ORCID: https://orcid.org/0000-0001-6883-5643)
- Jun Chen (ORCID: https://orcid.org/0000-0002-3850-4875)
- Hongying Chen (ORCID: https://orcid.org/0000-0001-8258-0683)
- Dong Pan (ORCID: https://orcid.org/0009-0003-4548-2082)
- Yongchen Liu (ORCID: https://orcid.org/0000-0002-1772-5572)
- Yabin Hu
- Xingyu Zheng
- Chanfeng Wu
- Yinggen Tang
- Fen Liu (ORCID: https://orcid.org/0009-0005-2469-7513)
- Qian Wu (ORCID: https://orcid.org/0009-0003-5273-6722)
Institutions
- Sun Yat-sen University (CN)
- North West Agriculture and Forestry University (CN)
- The Central Hospital of Shaoyang (CN)
- Chenzhou First People's Hospital (CN)
- Southern Medical University (CN)
- Northwest A&F University (CN)
- University of South China (CN)
Publication Details
- Journal
- npj Vaccines
- Published
- 2024-10-22
- DOI
- https://doi.org/10.1038/s41541-024-00997-8
- Citations
- 8
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 3.11
Funders
- European Commission
- National Natural Science Foundation of China
- Science and Technology Planning Project of Guangdong Province