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Antiviral Res. 2017 Aug;144:44-47. doi: 10.1016/j.antiviral.2017.05.007. Epub 2017 May 18.

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

Author information

1
Experimental Therapeutics Centre, Agency for Science, Technology and Research, Singapore; Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
2
Visterra Singapore International Pte Ltd, Singapore.
3
Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
4
Visterra Inc, Cambridge, MA, USA.
5
Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore; Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Singapore-MIT Alliance in Research and Technology, Infectious Diseases Interdisciplinary Research Group, Singapore. Electronic address: engeong.ooi@duke-nus.edu.sg.

Abstract

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.

KEYWORDS:

Antiviral efficacy; Dengue virus; Fc-gamma receptor; Non-human primate; Therapeutic monoclonal antibody

PMID:
28529000
DOI:
10.1016/j.antiviral.2017.05.007
[Indexed for MEDLINE]
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