The Mechanism of Antiviral Antibody in Limiting Viral Infection

Antiviral Antibodies

Antiviral antibodies are critical for host protection and are the basis of successful vaccines. The antibodies neutralize viruses by blocking the interaction between the virus and host cell through binding to free virus or binding to the required receptor on the cell surface for attaching and entering the virus into the cell. They also help to eliminate viral infections by representing the presented antigens on the infected target cell to the immune system effector cells. These cells permit the mechanisms as antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP) or a way known as complement-dependent cytotoxicity (CDC) to eliminate infected cells The vast majority of virus-specific antibodies, however, have no neutralizing activity. This is because they are elicited by virion fragments, or by viral proteins that are released from dying, infected cells. Nonneutralizing antibodies that bind to surface-accessible determinants have been shown to help to control certain virus infections by activating the complement system, augmenting ADCP and/or ADCC.

Fig.1 Mechanisms of action of the monoclonal antibodies with antiviral properties. (Flego, 2013)

Complement System

The complement system is a constituent of innate immunity that serves as a vital link between innate and adaptive immunity. It gets activated in most viral infections and leads to neutralization of virus via opsonization of C3b, aggregation, phagocytosis, membrane attack complex (MAC) mediated lysis of virus or virus-infected cells. Three general activation pathways, referred to as the classical, alternative, and lectin pathways, all converge on C3, the central component of the complement system. The classical complement pathway is initiated by the binding of the complement component C1q to antigen-antibody complexes with the antibody isotypes IgG and IgM, inducing antiviral activity. These viruses include human cytomegalovirus (HCMV) and certain retroviruses such as the human immunodeficiency virus (HIV).

Fig.2 Overview of the complement system. (Mellors, 2020)

Antiviral Antibody-based Therapies

Monoclonal antibodies (mAbs) owing to the unique properties of target specificity are an important class among therapeutic agents. mAb therapy is a form of passive immunotherapy that is classically intended to blunt viral infections via direct and rapid targeting of the infectious agent. So far, most antiviral mAbs with therapeutic potential have initially been selected for their ability to neutralize virions via the recognition of viral surface antigens essential for receptor binding and/or entry into host cells. However, there are few approved therapeutic mAbs for viral infections. In addition, the high cost associated with antibody therapies is prohibitive in prophylactic use of antibodies for intractable viruses such as HIV and influenza A virus for a large population, particularly in low-resource areas.

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References

1. Flego, M.; et al. Clinical development of monoclonal antibody-based drugs in HIV and HCV diseases. BMC medicine. 2013, 11(1): 1-17.
2. Mellors, J.; et al. Viral evasion of the complement system and its importance for vaccines and therapeutics. Frontiers in Immunology. 2020, 11: 1450.

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