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Preclinical evaluation of VIS513, a therapeutic antibody against dengue virus, in non-human primates
Antiviral Research ( IF 7.6 ) Pub Date : 2017-05-18 , DOI: 10.1016/j.antiviral.2017.05.007
Eugenia Z. Ong , Yadunanda Budigi , Hwee Cheng Tan , Luke N. Robinson , Kirk J. Rowley , Alexander Winnett , Sven Hobbie , Zachary Shriver , Gregory J. Babcock , Eng Eong Ooi

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.



中文翻译:

非人类灵长类动物中针对登革热病毒的治疗性抗体VIS513的临床前评估

尽管有有用的体内活性,但没有针对登革热病毒(DENV)的疗法在临床试验中显示出功效。本文中,我们探索了剂量和病毒学终点,以指导在非人灵长类动物(NHP)中进行泛血清型抗DENV IgG1抗体VIS513的人体试验设计。尽管在治疗后仍可检测到RNAemia,但在NHPs高峰期或高峰后服用VIS513可以中和传染性DENV。人IgG与猕猴Fc-γ受体的不同相互作用可能会延迟中和的DENV的清除。我们的研究结果表明,VIS513具有抗病毒作用,并在评估抗DENV生物制剂试验的病毒学终点时应重点考虑。

更新日期:2017-05-18
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