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.

• antiviral therapy
• DC
• Fc receptors
• immunotherapy
• immune complexes
• monoclonal antibodies
• vaccine-like effects
• vaccine strategies

This work was supported by grants from the ‘Ligue Nationale contre le Cancer’, the ‘Fondation ARC’, ‘Sidaction’ and the ‘Fondation pour la Recherche Médicale’. Jennifer Lambour, Mar Naranjo-Gomez, Marc Piechaczyk and Mireia Pelegrin are part of the ‘MabImprove Labex’, a public grant overseen by the French National Research Agency (ANR) as part of the ‘Investissements d’Avenir’ program (reference: ANR-10-LABX -53-01) that also supported this work. We are grateful to Drs Eric Kremer (Institute of Molecular Genetics of Montpellier, France) and Robert Hipskind (Institute of Molecular Genetics of Montpellier, France) for critical reading of the manuscript.