Preclinical evaluation of VIS513, a therapeutic antibody against dengue virus, in non-human primates

• Published in: Antiviral research Vol. 144; pp. 44 - 47
• Main Authors: Ong, Eugenia Z., Budigi, Yadunanda, Tan, Hwee Cheng, Robinson, Luke N., Rowley, Kirk J., Winnett, Alexander, Hobbie, Sven, Shriver, Zachary, Babcock, Gregory J., Ooi, Eng Eong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-08-2017
• Subjects: Animals; Antibodies, Viral - administration & dosage; Antiviral Agents - administration & dosage; Antiviral efficacy; Dengue - therapy; Dengue virus; Dengue Virus - immunology; Drug Evaluation, Preclinical; Fc-gamma receptor; Immunologic Factors - administration & dosage; Immunotherapy - methods; Macaca; Non-human primate; Therapeutic monoclonal antibody; Treatment Outcome; Antiviral efficacy; Dengue virus; Therapeutic monoclonal antibody; Fc-gamma receptor; Non-human primate
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2017.05.007

Despite useful in vivo activity, no therapeutic against dengue virus (DENV) has demonstrated efficacy in clinical trials. Herein, we explored dosing and virological endpoints to guide the design of human trials of VIS513, a pan-serotype anti-DENV IgG1 antibody, in non-human primates (NHPs). Dosing VIS513 pre- or post-peak viremia in NHPs neutralized infectious DENV although RNAemia remained detectable post-treatment; differential interaction of human IgGs with macaque Fc-gamma receptors may delay clearance of neutralized DENV. Our findings suggest useful antiviral utility of VIS513 and highlight an important consideration when evaluating virological endpoints of trials for anti-DENV biologics.
•VIS513 is an engineered pan-serotype anti-dengue virus (DENV) IgG1 antibody.•Dosing VIS513 pre- or post-peak viremia in NHPs led to neutralization of infectious DENV; despite persistence of RNAemia.•Differential affinity of human IgG1 and macaque Fc-gamma receptor may impede clearance of neutralized DENV.•This work guides the rationale for VIS513 dosing and virological endpoints in a human trial.