4.6 Article

A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection

Journal

JOURNAL OF IMMUNOLOGY
Volume 205, Issue 4, Pages 915-922

Publisher

AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.2000583

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Funding

  1. National Institute of Allergy and Infectious Diseases (NIAID) [R21 AI139813, U01 AI141990, HHSN272201700060C, 75N93019C00062, 5T32CA009547, R01AI104739]
  2. NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) [HHSN272201400008C]
  3. National Institutes of Health (NIH) [R01 AI127828]
  4. Defense Advanced Research Projects Agency [HR001117S0019]
  5. Collaborative Influenza Vaccine Innovation Centers [75N93019C00051]
  6. National Cancer Institute Cancer Center [P30 CA91842]
  7. National Center for Research Resources (an Institute for Clinical and Translational Science/Clinical and Translational Sciences Award) [UL1 TR000448]
  8. Helen Hay Whitney postdoctoral fellowship

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for millions of infections and hundreds of thousands of deaths globally. There are no widely available licensed therapeutics against SARS-CoV-2, highlighting an urgent need for effective interventions. The virus enters host cells through binding of a receptor-binding domain within its trimeric spike glycoprotein to human angiotensin-converting enzyme 2. In this article, we describe the generation and characterization of a panel of murine mAbs directed against the receptor-binding domain. One mAb, 2B04, neutralized wild-type SARS-CoV-2 in vitro with remarkable potency (half-maximal inhibitory concentration of <2 ng/ml). In a murine model of SARS-CoV-2 infection, 2B04 protected challenged animals from weight loss, reduced lung viral load, and blocked systemic dissemination. Thus, 2B04 is a promising candidate for an effective antiviral that can be used to prevent SARS-CoV-2 infection.

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