Julander Justin G, Anderson Nicole, Haese Nicole, Andoh Takeshi, Streblow Daniel N, Cortez Pierre, Carter Kara, Marniquet Xavier, Watson Hugh, Mandron Marie
Institute for Antiviral Research, Utah State University, Logan, UT, USA.
Institute for Antiviral Research, Utah State University, Logan, UT, USA.
Antiviral Res. 2022 Jun;202:105295. doi: 10.1016/j.antiviral.2022.105295. Epub 2022 Mar 24.
Chikungunya virus (CHIKV) has re-emerged as a significant human pathogen in the 21st century, causing periodic, and sometimes widespread, outbreaks over the past 15 years. Although mortality is very rare, a debilitating arthralgia is very common and may persist for months or years. There are no antivirals that are approved for the treatment of CHIKV infection, and current treatment options consist of supportive care only. Herein, we demonstrate the efficacy of a CHIKV-specific antibody in the prophylactic and therapeutic treatment of CHIKV in mouse models of disease. The fully human anti-CHIKV monoclonal Ab SVIR023 demonstrated broad in vitro activity against representative strains from the three major CHIKV clades. Therapeutic treatment with SVIR023 administered 1- or 3-days post-infection resulted in reduced virus in various tissues in a dose- and time-dependent manner. Prophylactic treatment up to 4 weeks prior to virus challenge was also effective in preventing disease in mice. Mice treated with SVIR023 and infected with CHIKV were resistant to secondary challenge and no evidence of antibody enhancement of disease was observed. Treatment with SVIR023 was effective in mouse models of CHIKV infection and disease and further evaluation towards clinical development is warranted.
基孔肯雅病毒(CHIKV)在21世纪再度成为一种重要的人类病原体,在过去15年中引发了周期性的、有时甚至是广泛的疫情。虽然死亡率非常低,但使人衰弱的关节痛却很常见,且可能持续数月或数年。目前尚无获批用于治疗CHIKV感染的抗病毒药物,当前的治疗选择仅包括支持性护理。在此,我们在疾病小鼠模型中证明了一种CHIKV特异性抗体在CHIKV预防和治疗中的有效性。全人源抗CHIKV单克隆抗体SVIR023对来自CHIKV三个主要分支的代表性毒株具有广泛的体外活性。感染后1天或3天给予SVIR023进行治疗,可使多种组织中的病毒量以剂量和时间依赖性方式减少。在病毒攻击前长达4周进行预防性治疗对预防小鼠疾病也有效。用SVIR023治疗并感染CHIKV的小鼠对二次攻击具有抵抗力,且未观察到疾病抗体增强的迹象。SVIR023治疗在CHIKV感染和疾病的小鼠模型中有效,值得进一步评估以推进临床开发。