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Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses

  1. Author:
    Banach, Bailey B.
    Cerutti, Gabriele
    Fahad, Ahmed S.
    Shen, Chen-Hsiang
    De Souza, Matheus Oliveira
    Katsamba, Phinikoula S.
    Tsybovsky, Yaroslav
    Wang, Pengfei
    Nair, Manoj S.
    Huang, Yaoxing
    Francino-Urdaniz, Irene M.
    Steiner, Paul J.
    Gutierrez-Gonzalez, Matias
    Liu, Lihong
    Acevedo, Sheila N. Lopez
    Nazzari, Alexandra F.
    Wolfe, Jacy R.
    Luo, Yang
    Olia, Adam S.
    Teng, I-Ting
    Yu, Jian
    Zhou, Tongqing
    Reddem, Eswar R.
    Bimela, Jude
    Pan, Xiaoli
    Madan, Bharat
    Laflin, Amy D.
    Nimrania, Rajani
    Yuen, Kwok-Yung
    Whitehead, Timothy A.
    Ho, David D.
    Kwong, Peter D.
    Shapiro, Lawrence
    DeKosky, Brandon J.

  2. Author Address

    Univ Kansas, Bioengn Grad Program, Lawrence, KS 66045 USA.Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.Univ Kansas, Dept Pharmaceut Chem, Lawrence, KS 66045 USA.NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.Frederick Natl Lab Canc Res, Electron Microscopy Lab, Canc Res Technol Program, Leidos Biomed Res, Frederick, MD 21702 USA.Columbia Univ, Aaron Diamond AIDS Res Ctr, Vagelos Coll Phys & Surg, New York, NY 10032 USA.Univ Colorado, Dept Chem & Biol Engn, Boulder, CO 80305 USA.Columbia Univ, Zuckerman Mind Brain Behav Inst, New York, NY 10027 USA.Univ Hong Kong, Li Ka Shing Fac Med, Carol Yu Ctr Infect, Dept Microbiol,State Key Lab Emerging Infect Dis, Hong Kong, Peoples R China.Queen Mart Hosp, Dept Microbiol, Hong Kong, Peoples R China.Univ Hong Kong, Dept Clin Microbiol & Infect Control, Shenzhen Hosp, Shenzhen, Peoples R China.Univ Kansas, Dept Chem Engn, Lawrence, KS 66045 USA.
    1. Year: 2021
    2. Date: Oct 5
    3. Epub Date: 2021 Sep 28
  2. Journal: Cell Reports
  3. Cell Press
    1. 37
    2. 1
  5. Type of Article: Article
  6. Article Number: ARTN 109771
  7. ISSN: 2211-1247
  1. Abstract:

    Understanding mechanisms of protective antibody recognition can inform vaccine and therapeutic strategies against SARS-CoV-2. We report a monoclonal antibody, 910-30, targeting the SARS-CoV-2 receptor-binding site for ACE2 as a member of a public antibody response encoded by IGHV3-53/IGHV3-66 genes. Sequence and structural analyses of 910-30 and related antibodies explore how class recognition features correlate with SARS-CoV-2 neutralization. Cryo-EMstructures of 910-30 bound to the SARS-CoV-2 spike trimer reveal binding interactions and its ability to disassemble spike. Despite heavy-chain sequence similarity, biophysical analyses of IGHV3-53/3-66-encoded antibodies highlight the importance of native heavy:light pairings for ACE2-binding competition and SARS-CoV-2 neutralization. We develop paired heavy:light class sequence signatures and determine antibody precursor prevalence to be similar to 1 in 44,000 human B cells, consistent with public antibody identification in several convalescent COVID-19 patients. These class signatures reveal genetic, structural, and functional immune features that are helpful in accelerating antibody-based medical interventions for SARS-CoV-2.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.celrep.2021.109771
  3. PMID: 34587480
  4. PMCID: PMC8479507
  5. View record in Web of Science®
  6. WOS: 000704665900006

Library Notes

  1. Fiscal Year: FY2021-2022
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