title: A Structural and Mathematical Modeling Analysis of the Likelihood of Antibody-Dependent Enhancement in Influenza.
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.
authors.affiliation: Visterra, Inc. One Kendall Square, Suite B3301, Cambridge, MA 02139, USA.
authors.forename: Boopathy
authors.initials: B
authors.lastname: Ramakrishnan
authors.affiliation: Visterra, Inc. One Kendall Square, Suite B3301, Cambridge, MA 02139, USA.
authors.forename: Karthik
authors.initials: K
authors.lastname: Viswanathan
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 01890, USA.
authors.forename: Kannan
authors.initials: K
authors.lastname: Tharakaraman
authors.affiliation: Center for the Science of Therapeutics, Broad Institute, Cambridge, MA 02142, USA.
authors.forename: Vlado
authors.initials: V
authors.lastname: Dančík
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 01890, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Raman
authors.affiliation: Visterra, Inc. One Kendall Square, Suite B3301, Cambridge, MA 02139, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Babcock
authors.affiliation: Visterra, Inc. One Kendall Square, Suite B3301, Cambridge, MA 02139, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Shriver
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 01890, USA. Electronic address: rams@mit.edu.
authors.forename: Ram
authors.initials: R
authors.lastname: Sasisekharan
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000276:immunology* / Q000627:therapeutic use; D019067:Antibody-Dependent Enhancement; D003715:Dengue / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007251:Influenza, Human / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D008954:Models, Biological; D008958:Models, Molecular; D014766:Viremia / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes