Fc gamma receptor activation during viral infections: a double-edged sword

Over the last several decades, antibodies (Abs) have become a valuable weapon in the fight against viral infections, with several studies demonstrating the importance of both neutralizing and non-neutralizing Ab responses in preventing or controlling viral infections in-vivo. Fc receptor mediated non-neutralizing effector functions such as, Ab-dependent Cellular Cytotoxicity (ADCC), phagocytosis and cytokine expression, have all been shown to contribute to effective immune responses in-vivo. However, in the case of some viral infections, such as dengue, Ab/Fc receptor mediated interactions enhance the severity of dengue hemorrhagic fever via Antibody Dependent Enhancement (ADE), which is hypothesized to primarily occur via Fc gamma receptor (FcγR) interactions. Importantly, in the context of the current SARS CoV-2 pandemic, researchers have observed that disease severity correlates with anti-SARS CoV-2 spike protein levels. Further, previous studies on a SARS1 vaccine suggest that ADE may contribute to mortality in animal models. These findings have important implications for anti-spike based SARS CoV-2 therapeutics and vaccine approaches. Therefore, our laboratory has begun to profile the levels of FcγR activation in a cohort of SARS CoV-2 convalescent patients versus severe hospitalized patients, to begin to understand whether ADE is a primary driver of severity and mortality during COVID-19 disease.

Learning objectives:

1. To learn how non-neutralizing Ab responses contribute to immune regulation during viral infections

2. To learn how in the majority of viral infections, non-neutralizing antibodies help to potently control infections in-vivo

3. To learn that in the context of certain viral infections, such as dengue, non-neutralizing Ab functions can be detrimental to the host and enhance severity of disease