Converting monoclonal antibody-based immunotherapies from passive to active: bringing immune complexes into play

Abstract

Monoclonal antibodies (mAbs), which currently constitute the main class of biotherapeutics, are now recognized as major medical tools that are increasingly being considered to fight severe viral infections. Indeed, the number of antiviral mAbs developed in recent years has grown exponentially. Although their direct effects on viral blunting have been studied in detail, their potential immunomodulatory actions have been overlooked until recently. The ability of antiviral mAbs to modulate antiviral immune responses in infected organisms has recently been revealed. More specifically, upon recognition of their cognate antigens, mAbs form immune complexes (ICs) that can be recognized by the Fc receptors expressed on different immune cells of infected individuals. This binding may be followed by the modulation of the host immune responses. Harnessing this immunomodulatory property may facilitate improvements in the therapeutic potential of antiviral mAbs. This review focuses on the role of ICs formed with different viral determinants and mAbs in the induction of antiviral immune responses in the context of both passive immunotherapies and vaccination strategies. Potential deleterious effects of ICs on the host immune response are also discussed.

Promising approaches for the treatment and prevention of viral respiratory illnesses

“…95 Neutralizing antibodies can bind and inactivate viruses, inhibit viral cell entry (blocking receptor binding or conformational changes), prevent the release of virions from the cell, or modulate immune effector functions. 96,97 Engineering and production strategies to produce antibody fragments, higher-affinity binding, and longer half-life are contributing to a lower overall cost for therapy, 95 although vaccines are still considered preferable in most cases. It is notable that effective neutralizing mAb epitopes can also inform the rational design of vaccines.…”

Neutrophils are essential for induction of vaccine-like effects by antiviral monoclonal antibody immunotherapies

“…Notably, in addition to antirespiratory syncytial virus (RSV) mAb used to treat infant respiratory disease, several mAbs directed against human cytomegalovirus, HIV, influenza, Ebola, and rabies virus are currently engaged in promising clinical trials (1,3,9,14). While the direct effects of antiviral mAbs on viral propagation have been studied extensively, little attention has been paid to their potential immunomodulatory effects until recently (10,15,16).…”

Patterns of HIV/SIV Prevention and Control by Passive Antibody Immunization

“…Conversely, late-phase polyclonal NAb infusion in immunocompromised SIV-infected rapid progressors showed no protective effect (Binley et al, 2000), suggesting the importance of intact endogenous immunity for NAb-mediated viral suppression. Taken together, results collectively show that NAbs provide a wide spectrum of protective mechanisms in vivo , particularly those involving Fc receptors (Lambour et al, 2016), against AIDS virus replication.…”