Antibody potency, effector function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo

Area of Science:

• Virology
• Immunology
• Pharmacology

Background:

• Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes COVID-19, a global pandemic with significant mortality.
• Limited therapeutic options and no approved vaccines necessitate the development of effective treatments.

Purpose of the Study:

• To evaluate the efficacy of human monoclonal antibodies (hu-mAbs) against SARS-CoV-2 in animal models.
• To determine the correlation between in vitro neutralization and in vivo protection.
• To investigate the role of antibody Fc regions and effector functions in protection.

Main Methods:

• Utilized Syrian hamster and mouse-adapted SARS-CoV-2 (SARS-CoV-2 MA) infection models.
• Administered single and combination hu-mAb therapies for prevention and early treatment.
• Analyzed antibody Fc region binding to Fc receptors and assessed in vivo protective activity.

Main Results:

• Antibody combinations demonstrated effectiveness in both prevention and early therapy.
• In vitro neutralization potency did not consistently correlate with in vivo protection.
• Fc region binding to activating Fc receptors was linked to optimal protection against SARS-CoV-2 MA.
• Some hu-mAbs showed enhanced protection in combination therapy.

Conclusions:

• Intact Fc effector function is critical for optimal hu-mAb protective activity against SARS-CoV-2.
• In vivo efficacy testing is essential for identifying optimal hu-mAb combinations for COVID-19.
• Further research into Fc-mediated mechanisms can guide the development of superior antibody therapies.