Molecular deconvolution of the neutralizing antibodies induced by an inactivated SARS-CoV-2 virus vaccine

doi:10.1007/s13238-021-00840-z

. 2021 Oct;12(10):818-823.

doi: 10.1007/s13238-021-00840-z. Epub 2021 Apr 28.

Molecular deconvolution of the neutralizing antibodies induced by an inactivated SARS-CoV-2 virus vaccine

Xingdong Zhou^#^{1

2}, Hui Wang^#³, Qun Ji², Mingjuan Du², Yuexia Liang¹, Huanhuan Li¹, Fan Li¹, Hang Shang¹, Xiujuan Zhu³, Wei Wang², Lichun Jiang², Alexey V Stepanov⁴, Tianyu Ma¹, Nanxin Gong¹, Xiaodong Jia⁵, Alexander G Gabibov⁴, Zhiyong Lou⁶, Yinying Lu⁷, Yu Guo⁸, Hongkai Zhang^{9

10}, Xiaoming Yang¹¹

Affiliations

¹ State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin, 300071, China.
² Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210, China.
³ Beijing Institute of Biological Products Company Limited, Beijing, 100176, China.
⁴ M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia, 117997.
⁵ Comprehensive Liver Cancer Center, The 5th Medical Center of PLA General Hospital, Beijing, 100039, China.
⁶ MOE Key Laboratory of Protein Science & Collaborative Innovation Center of Biotherapy, School of Medicine, Tsinghua University, Beijing, 100084, China. louzy@mail.tsinghua.edu.cn.
⁷ Comprehensive Liver Cancer Center, The 5th Medical Center of PLA General Hospital, Beijing, 100039, China. Luyinying1973@163.com.
⁸ State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin, 300071, China. guoyu@nankai.edu.cn.
⁹ State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin, 300071, China. hongkai@nankai.edu.cn.
¹⁰ Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210, China. hongkai@nankai.edu.cn.
¹¹ Beijing Institute of Biological Products Company Limited, Beijing, 100176, China. yangxiaoming@sinopharm.com.

^# Contributed equally.

PMID: 33909239
PMCID: PMC8080482
DOI: 10.1007/s13238-021-00840-z

Molecular deconvolution of the neutralizing antibodies induced by an inactivated SARS-CoV-2 virus vaccine

Xingdong Zhou et al. Protein Cell. 2021 Oct.

. 2021 Oct;12(10):818-823.

doi: 10.1007/s13238-021-00840-z. Epub 2021 Apr 28.

Authors

Affiliations

¹ State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin, 300071, China.
² Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210, China.
³ Beijing Institute of Biological Products Company Limited, Beijing, 100176, China.
⁴ M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia, 117997.
⁵ Comprehensive Liver Cancer Center, The 5th Medical Center of PLA General Hospital, Beijing, 100039, China.
⁶ MOE Key Laboratory of Protein Science & Collaborative Innovation Center of Biotherapy, School of Medicine, Tsinghua University, Beijing, 100084, China. louzy@mail.tsinghua.edu.cn.
⁷ Comprehensive Liver Cancer Center, The 5th Medical Center of PLA General Hospital, Beijing, 100039, China. Luyinying1973@163.com.
⁸ State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin, 300071, China. guoyu@nankai.edu.cn.
⁹ State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin, 300071, China. hongkai@nankai.edu.cn.
¹⁰ Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210, China. hongkai@nankai.edu.cn.
¹¹ Beijing Institute of Biological Products Company Limited, Beijing, 100176, China. yangxiaoming@sinopharm.com.

^# Contributed equally.

PMID: 33909239
PMCID: PMC8080482
DOI: 10.1007/s13238-021-00840-z

No abstract available

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Figures

**Figure 1**
**SARS-CoV-2-specific response in human vaccination**. (A) Immunization and blood collection regimen. (B) Binding of plasma from donor 1 and donor 2 to SARS-CoV-2 S protein, as determined by ELISA. The mean values and SDs of three technical replicates are shown. (C) Neutralization of two SARS-CoV-2 strains (QD01 and P701) by plasma from donor 1 and donor 2. The mean values and SDs of two technical replicates are shown. (D) Violin plot showing SHM levels (nucleotides) of each donor. The lower, middle and upper edges of the boxplots represent the 25th, 50th and 75th percentiles, respectively. (E) Distribution of heavy chain CDR3 lengths in B cells from vaccinated and naïve donors. (F) Bar graph showing VH germline usage (%) in vaccinated and naïve donors. (G) Outline of microfluidics-based construction of a natively paired VH:VL antibody repertoire. Isolated B cells were purified from blood samples and encapsulated into water-in-oil droplets with beads for mRNA capture. mRNA-captured beads and RT-PCR reagents were reencapsulated, resulting in an amplicon-derived scFv library that can be screened by phage display technology. (H) Schematic of OE-PCR to construct natively paired VH:VL antibody libraries. VH and VL from each encapsulated B cell mRNA are amplified with specific primer sets and paired in-frame via complementary overhangs (yellow). A nested PCR with VH and CL primers generates full-length scFv with SfiI restriction sites for subcloning into phagemid vectors for library generation

**Figure 2**
**Characterization of isolated S protein-reactive antibodies**. Sequence information of the identified neutralizing antibodies. 1-0106 is named for clone 1-0106 isolated from donor 1. Midpoint neutralization concentrations (IC₅₀) for four SARS-CoV-2 strains (QD01/P701/HN97/F13). Each symbol represents an individual antibody. A competition assay was performed among different antibodies for binding to the RBD. The immobilized RBD was first incubated with 1-106, 1-108, 2-0126, 2-0139 or 2-01H5. The capture of the second antibodies was monitored by measuring further changes after injecting the second antibody in the presence of the first antibody. (D) Binding of each antibody to RBD and S protein mutants

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References

1. Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene M, Chappell JD, Denison MR, Stevens LJ, Pruijssers AJ, et al. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N Engl J Med. 2020;383:2427–2438. doi: 10.1056/NEJMoa2028436. - DOI - PMC - PubMed
1. Brouwer PJM, Caniels TG, van der Straten K, Snitselaar JL, Aldon Y, Bangaru S, Torres JL, Okba NMA, Claireaux M, Kerster G, et al. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science. 2020;369:643–650. doi: 10.1126/science.abc5902. - DOI - PMC - PubMed
1. Cao Y, Su B, Guo X, Sun W, Deng Y, Bao L, Zhu Q, Zhang X, Zheng Y, Geng C, et al. Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput Single-cell sequencing of convalescent patients’ B cells. Cell. 2020;182:73–84. doi: 10.1016/j.cell.2020.05.025. - DOI - PMC - PubMed
1. Jones I, Roy P. Sputnik V COVID-19 vaccine candidate appears safe and effective. Lancet. 2021;397(10275):642–643. doi: 10.1016/S0140-6736(21)00191-4. - DOI - PMC - PubMed
1. Ju B, Zhang Q, Ge J, Wang R, Sun J, Ge X, Yu J, Shan S, Zhou B, Song S, et al. Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature. 2020;584:115–119. doi: 10.1038/s41586-020-2380-z. - DOI - PubMed

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[1] Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene M, Chappell JD, Denison MR, Stevens LJ, Pruijssers AJ, et al. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N Engl J Med. 2020;383:2427–2438. doi: 10.1056/NEJMoa2028436. - DOI - PMC - PubMed

[2] Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene M, Chappell JD, Denison MR, Stevens LJ, Pruijssers AJ, et al. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N Engl J Med. 2020;383:2427–2438. doi: 10.1056/NEJMoa2028436. - DOI - PMC - PubMed

[3] Brouwer PJM, Caniels TG, van der Straten K, Snitselaar JL, Aldon Y, Bangaru S, Torres JL, Okba NMA, Claireaux M, Kerster G, et al. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science. 2020;369:643–650. doi: 10.1126/science.abc5902. - DOI - PMC - PubMed

[4] Brouwer PJM, Caniels TG, van der Straten K, Snitselaar JL, Aldon Y, Bangaru S, Torres JL, Okba NMA, Claireaux M, Kerster G, et al. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science. 2020;369:643–650. doi: 10.1126/science.abc5902. - DOI - PMC - PubMed

[5] Cao Y, Su B, Guo X, Sun W, Deng Y, Bao L, Zhu Q, Zhang X, Zheng Y, Geng C, et al. Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput Single-cell sequencing of convalescent patients’ B cells. Cell. 2020;182:73–84. doi: 10.1016/j.cell.2020.05.025. - DOI - PMC - PubMed

[6] Cao Y, Su B, Guo X, Sun W, Deng Y, Bao L, Zhu Q, Zhang X, Zheng Y, Geng C, et al. Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput Single-cell sequencing of convalescent patients’ B cells. Cell. 2020;182:73–84. doi: 10.1016/j.cell.2020.05.025. - DOI - PMC - PubMed

[7] Jones I, Roy P. Sputnik V COVID-19 vaccine candidate appears safe and effective. Lancet. 2021;397(10275):642–643. doi: 10.1016/S0140-6736(21)00191-4. - DOI - PMC - PubMed

[8] Jones I, Roy P. Sputnik V COVID-19 vaccine candidate appears safe and effective. Lancet. 2021;397(10275):642–643. doi: 10.1016/S0140-6736(21)00191-4. - DOI - PMC - PubMed

[9] Ju B, Zhang Q, Ge J, Wang R, Sun J, Ge X, Yu J, Shan S, Zhou B, Song S, et al. Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature. 2020;584:115–119. doi: 10.1038/s41586-020-2380-z. - DOI - PubMed

[10] Ju B, Zhang Q, Ge J, Wang R, Sun J, Ge X, Yu J, Shan S, Zhou B, Song S, et al. Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature. 2020;584:115–119. doi: 10.1038/s41586-020-2380-z. - DOI - PubMed

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Molecular deconvolution of the neutralizing antibodies induced by an inactivated SARS-CoV-2 virus vaccine

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Molecular deconvolution of the neutralizing antibodies induced by an inactivated SARS-CoV-2 virus vaccine

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