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Possible future monoclonal antibody (mAb)-based therapy against arbovirus infections - PubMed

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Review

Possible future monoclonal antibody (mAb)-based therapy against arbovirus infections

Giuseppe Sautto et al. Biomed Res Int. 2013.

Abstract

More than 150 arboviruses belonging to different families are known to infect humans, causing endemic infections as well as epidemic outbreaks. Effective vaccines to limit the occurrence of some of these infections have been licensed, while for the others several new immunogens are under development mostly for their improvements concerning safety and effectiveness profiles. On the other hand, specific and effective antiviral drugs are not yet available, posing an urgent medical need in particular for emergency cases. Neutralizing monoclonal antibodies (mAbs) have been demonstrated to be effective in the treatment of several infectious diseases as well as in preliminary in vitro and in vivo models of arbovirus-related infections. Given their specific antiviral activity as well-tolerated molecules with limited side effects, mAbs could represent a new therapeutic approach for the development of an effective treatment, as well as useful tools in the study of the host-virus interplay and in the development of more effective immunogens. However, before their use as candidate therapeutics, possible hurdles (e.g., Ab-dependent enhancement of infection, occurrence of viral escape variants) must be carefully evaluated. In this review are described the main arboviruses infecting humans and candidate mAbs to be possibly used in a future passive immunotherapy.

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Figures

Figure 1
Figure 1

Mechanisms of antibody-dependent enhancement (ADE) of infection. (a) After binding to the viral epitope, the Ab is recognized by a cellular Fc-γ receptor, bringing the viral particle in proximity of the target cell; (b) the binding of the Ab induces conformational changes within the structure of the viral target protein. These changes improve the affinity for the cellular receptor; (c) molecular mimicry by a viral motif of cellular membrane components leads an autoreactive Ab to bind both the viral and the cellular target, bringing the virus in proximity of the target cell.

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