Building a better antibody through the Fc: advances and challenges in harnessing antibody Fc effector functions for antiviral protection

ABSTRACT

Antibodies can provide antiviral protection through neutralization and recruitment of innate effector functions through the Fc domain. While neutralization has long been appreciated for its role in antibody-mediated protection, a growing body of work indicates that the antibody Fc domain also significantly contributes to antiviral protection. Recruitment of innate immune cells such as natural killer cells, neutrophils, monocytes, macrophages, dendritic cells and the complement system by antibodies can lead to direct restriction of viral infection as well as promoting long-term antiviral immunity. Monoclonal antibody therapeutics against viruses are increasingly incorporating Fc-enhancing features to take advantage of the Fc domain, uncovering a surprising breadth of mechanisms through which antibodies can control viral infection. Here, we review the recent advances in our understanding of antibody-mediated innate immune effector functions in protection from viral infection and review the current approaches and challenges to effectively leverage innate immune cells via antibodies.

KEYWORDS:

• Antibodies
• effector functions
• innate immunity
• antibody engineering
• antibody Fc domain
• virus
• antiviral
• immuno-therapeutics
• Ebola virus
• SARS-CoV-2
• influenza

Acknowledgments

We would like to thank members of the Gunn Lab for helpful discussions. We would like to acknowledge funding support from the National Institutes of Allergy and Infectious Diseases U19AI142777, the National Cancer Institute U54CA260581, and the Washington State University College of Veterinary Medicine Intramural Research Grant Fund. Figures were generated with an academic publishing license in Biorender.

Disclosure of potential conflicts of interest

The authors have declared that there are no conflicts of interest.