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Trends Microbiol. 2016 Dec;24(12):933-943. doi: 10.1016/j.tim.2016.09.003. Epub 2016 Oct 14.

A Structural and Mathematical Modeling Analysis of the Likelihood of Antibody-Dependent Enhancement in Influenza.

Author information

1
Visterra, Inc. One Kendall Square, Suite B3301, Cambridge, MA 02139, USA.
2
Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 01890, USA.
3
Center for the Science of Therapeutics, Broad Institute, Cambridge, MA 02142, USA.
4
Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 01890, USA. Electronic address: rams@mit.edu.

Abstract

Broadly neutralizing monoclonal antibodies (bNAbs) for viral infections, such as HIV, respiratory syncytial virus (RSV), and influenza, are increasingly entering clinical development. For influenza, most neutralizing antibodies target influenza virus hemagglutinin. These bNAbs represent an emerging, promising modality for treatment and prophylaxis of influenza due to their multiple mechanisms of antiviral action and generally safe profile. Preclinical work in other viral diseases, such as dengue, has demonstrated the potential for antibody-based therapies to enhance viral uptake, leading to enhanced viremia and worsening of disease. This phenomenon is referred to as antibody-dependent enhancement (ADE). In the context of influenza, ADE has been used to explain several preclinical and clinical phenomena. Using structural and viral kinetics modeling, we assess the role of ADE in the treatment of influenza with a bNAb.

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