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A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2.

ABSTRACT: Neutralizing antibodies could potentially be used as antivirals against the coronavirus disease 2019 (COVID-19) pandemic. Here, we report isolation of four human-origin monoclonal antibodies from a convalescent patient, all of which display neutralization abilities. The antibodies B38 and H4 block binding between the spike glycoprotein receptor binding domain (RBD) of the virus and the cellular receptor angiotensin-converting enzyme 2 (ACE2). A competition assay indicated different epitopes on the RBD for these two antibodies, making them a potentially promising virus-targeting monoclonal antibody pair for avoiding immune escape in future clinical applications. Moreover, a therapeutic study in a mouse model validated that these antibodies can reduce virus titers in infected lungs. The RBD-B38 complex structure revealed that most residues on the epitope overlap with the RBD-ACE2 binding interface, explaining the blocking effect and neutralizing capacity. Our results highlight the promise of antibody-based therapeutics and provide a structural basis for rational vaccine design.

SUBMITTER: Wu Y

PROVIDER: S-EPMC7223722 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2.

Wu Yan Y Wang Feiran F Shen Chenguang C Peng Weiyu W Li Delin D Zhao Cheng C Li Zhaohui Z Li Shihua S Bi Yuhai Y Yang Yang Y Gong Yuhuan Y Xiao Haixia H Fan Zheng Z Tan Shuguang S Wu Guizhen G Tan Wenjie W Lu Xuancheng X Fan Changfa C Wang Qihui Q Liu Yingxia Y Zhang Chen C Qi Jianxun J Gao George Fu GF Gao Feng F Liu Lei L

Science (New York, N.Y.) 20200513 6496

Neutralizing antibodies could potentially be used as antivirals against the coronavirus disease 2019 (COVID-19) pandemic. Here, we report isolation of four human-origin monoclonal antibodies from a convalescent patient, all of which display neutralization abilities. The antibodies B38 and H4 block binding between the spike glycoprotein receptor binding domain (RBD) of the virus and the cellular receptor angiotensin-converting enzyme 2 (ACE2). A competition assay indicated different epitopes on t ...[more]

PMID: 32404477

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Project description:New World arenaviruses are rodent-transmitted viruses and include a number of pathogens that are responsible for causing severe human disease. This includes Junín virus (JUNV), which is the causative agent of Argentine hemorrhagic fever. The wild nature and mobility of the rodent reservoir host makes it difficult to control the disease, and currently passive immunization with high-titer neutralizing antibody-containing plasma from convalescent patients is the only specific therapy. However, dwindling supplies of naturally available convalescent plasma, and challenges in developing similar resources for other closely related viruses, have made the development of alternative antibody-based therapeutic approaches of critical importance. In this study, we sought to induce a neutralizing antibody response in rabbits against the receptor-binding subunit of the viral glycoprotein, GP1, and the specific peptide sequences in GP1 involved in cellular receptor contacts. While these specific receptor-interacting peptides did not efficiently induce the production of neutralizing antibodies when delivered as a particulate antigen (as part of hepatitis B virus core-like particles), we showed that recombinant JUNV GP1 purified from transfected mammalian cells induced virus-neutralizing antibodies at high titers in rabbits. Further, neutralization was observed across a range of unrelated JUNV strains, a feature that is critical for effectiveness in the field. These results underscore the potential of GP1 alone to induce a potent neutralizing antibody response and highlight the importance of epitope presentation. In addition, effective virus neutralization by rabbit antibodies supports the potential applicability of this species for the future development of immunotherapeutics (e.g., based on humanized monoclonal antibodies). Such information can be applied in the design of vaccines and immunogens for both prevention and specific therapies against this and likely also other closely related pathogenic New World arenaviruses.

Dataset Information

A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2.

Publications

A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2.

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