Possible mechanisms of action of the mAbs with antiviral properties. Panel A shows a hypothetical viral life cycle, highlighting potential points for therapeutic antiviral mAbs. Antibodies can block receptor engagement by binding to specific virus surface proteins (1), as well as by binding to the viral receptor or co-receptor on host cell surface (2). Some antibodies, can neutralize viral infection through interfering with conformational changes required for membrane fusion and subsequent release of the viral core into the target-cell cytoplasm; this post-binding neutralization may occur at the cell surface (3), or inside the endosomes for the viruses (for example, HCV) whose entry into the cell requires an endocytosis step (4). Antibodies recognizing viral or host proteins expressed on infected cell surface can exert protective actions through the Fc-mediated effector functions (for example, CDC, ADCC) (5). Again, mAbs may prevent the release of progeny virions (6). At the bottom the antibody neutralizing effects on the viruses before cell binding, including the direct virolysis by CDC and the mAb-mediated enhanced phagocitosis, are shown (7). In Panel B, the possible mAb-mediated immunomodulary therapies are depicted. In some chronic viral infections, virus-specific immune cells may persist in a 'non-functional' state, because of an imbalance of immunoregulatory signals involving multiple inhibitory and activating receptors, triggered by soluble factors and/or cell surface ligands. Therapeutic approaches using specific mAbs to block host immunosuppressive molecules (antagonism) or to trigger activating receptors (agonism) may be a valid strategy to restore immune cell function and treat various chronic viral infections.
Flego et al. BMC Medicine 2013 11:4 doi:10.1186/1741-7015-11-4