Enhancement of antiviral effectiveness against viral respiratory pathogens by engineering Fc domain of antibodies

-Richismita Hazra, Amity University Kolkata

Antibodies serve as analytical barriers to viruses or viral infections. They play a dual role in communicating the existence of invading pathogens in infected cells, also, in interfering with the processes that are essential to the viral lifecycle. The antibodies activate phagocytes which is a potential mechanism of eradiating viruses. A virus-bound antibody binds to receptors, on the surface of phagocytic cells and undergoes phagocytosis thereby engulfing and hence destroying the virus.

So, antibodies against viral pathogens have proved remedial processes for the control of infections and researches from the past have entrenched that their antiviral potency is based on the combined effectiveness or functioning of Fab and Fc domains.

The Fragment Antigen-Binding fragment (Fab) is the region of an antibody to which the antigens bind.

The Fragment Crystallizable (Fc) region plays a role in modulating immune cell activity. This region binds to specific proteins and establishes the fact that each antibody generates an appropriate immune response for a particular antigen. By binding to Fc receptors (FcγRs) and other immune molecules, the Fc domain mediates various physiological effects like cell lysis and triggers the clearance of virus and destruction of infected cells. This research reports that when Fc of the anti-influenza IgG monoclonal antibodies (mAbs) is engineered for selective binding to the activating FcγR, FcγRIIa, it results in an improvement in the prevention or treatment of lethal viral respiratory infection with upgraded dendritic cell maturation and induction of protective CD8⁺ T-cell responses. This research highlights that IgG antibodies have the capability of promoting protective adaptive immunity towards viral infections on selective activation of dendritic cell-T cell pathway. This has a remarkable influence on the development of antibody therapeutics with upgraded antiviral effectiveness against viral respiratory pathogens.

Source: DOI https://doi.org/10.1038/s41586-020-2838-z

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