Antiviral Activity of Antibody In Vitro
In vitro, antiviral activity can be separated into activity against virions and activity against infected cells. The activity against virions most often considered is neutralization. Antibody-dependent complement-mediated virolysis (ADCMV) is also an activity directed against free virions. Antibodies can also bind to viral products on infected cells to trigger effector functions, including activation of complement and antibody-dependent cellular cytotoxicity (ADCC).
Fig.1 Multiple Fc-mediated activities of antiviral monoclonal antibodies. (Lambour, 2016)
Antiviral Activity Against Virions
- Neutralization
Neutralization is the reduction and loss of virus infectivity caused by antibodies, thereby blocking a step in the viral replication cycle that precedes virally encoded transcription or synthesis. There have been multiple attempts to define the mechanisms of neutralization. These mechanisms include aggregation, inhibition of viral entry by inhibition of attachment, and inhibition of fusion with the target cell, as well as post-entry mechanisms, such as interference with primary and secondary uncoating of the genetic information of the virus.
- ADCMV
When viruses are exposed to a source of complement, complement activation can either directly mediate the neutralization of viruses or augment antibody-dependent neutralization. Specific antibody alone can efficiently neutralize many viruses, but complement activation can enhance the antiviral effects of antibodies by opsonizing virions or inducing lysis of the particles (Fig.2C). ADCMV can directly neutralize virus particles through opsonization and membrane attack complex (MAC) formation on the virion. There has been considerable research describing ADCMV and the anti-virolytic evasion methods employed by many enveloped viruses, such as HIV.
Antiviral Activity Against Infected cells
- ADCC
ADCC is triggered by the binding of the Fc segment of antibodies to the Fc receptors (FcRs) on effector cells thereby inducing effector cells to release cytotoxic substances such as perforin and granzymes. Therefore, ADCC responses to viral infection are a form of antibody-regulated immune responses mediated through the Fc fragment. The ADCC activity can contribute to viral clearance through the killing and removal of infected cells.
- Complement-Dependent Cytotoxicity
Complement is activated by antibodies IgG and IgM through activation of the classical pathway to induce complement-dependent cytotoxicity (CDC). The complement system can directly neutralize virus particles through MAC formation on virus-infected cells or targeting intracellular viral components for proteasomal degradation.
Fig.2 Mechanisms by which antibodies mediate effector functions. (Florese, 2007)
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References
- Lambour, J.; et al. Converting monoclonal antibody-based immunotherapies from passive to active: bringing immune complexes into play. Emerging microbes & infections. 2016, 5(1): 1-9.
- Florese, R.H.; Robert-Guroff, M. Non-neutralizing antibodies and vaccine-induced protection against HIV. Future Medicine. 2007, 1(3): 259-271.
