COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models

Nat Commun. 2021 Oct 20;12(1):6097. doi: 10.1038/s41467-021-26354-0.

Abstract

Effective treatments against Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Monoclonal antibodies have shown promising results in patients. Here, we evaluate the in vivo prophylactic and therapeutic effect of COVA1-18, a neutralizing antibody highly potent against the B.1.1.7 isolate. In both prophylactic and therapeutic settings, SARS-CoV-2 remains undetectable in the lungs of treated hACE2 mice. Therapeutic treatment also causes a reduction in viral loads in the lungs of Syrian hamsters. When administered at 10 mg kg-1 one day prior to a high dose SARS-CoV-2 challenge in cynomolgus macaques, COVA1-18 shows very strong antiviral activity in the upper respiratory compartments. Using a mathematical model, we estimate that COVA1-18 reduces viral infectivity by more than 95% in these compartments, preventing lymphopenia and extensive lung lesions. Our findings demonstrate that COVA1-18 has a strong antiviral activity in three preclinical models and could be a valuable candidate for further clinical evaluation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics
  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Neutralizing / administration & dosage*
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / pharmacokinetics
  • COVID-19 / blood
  • COVID-19 / immunology
  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Female
  • Humans
  • Lung / metabolism
  • Lung / virology
  • Macaca fascicularis
  • Male
  • Mesocricetus
  • Mice
  • Mice, Transgenic
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / isolation & purification
  • Tissue Distribution
  • Viral Load

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antiviral Agents
  • COVA1-18
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2