Integrated Research Facility at Fort Detrick, Division of Clinical Research (DCR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Ft. Detrick, Frederick, MD, 21702, USA.
Biostatistics Research Branch (BRB), Division of Clinical Research (DCR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
Antiviral Res. 2024 Oct;230:105987. doi: 10.1016/j.antiviral.2024.105987. Epub 2024 Aug 13.
The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and onset of the coronavirus disease-19 (COVID-19) pandemic led to an immediate need for therapeutic treatment options. Therapeutic antibodies were developed to fill a gap when traditional antivirals were not available. In late 2020, the United States Government undertook an effort to compare candidate therapeutic antibodies in virus neutralization assays and in the hamster model of SARS-CoV-2 infection. With the emergence of SARS-CoV-2 variants, the effort expanded to evaluate the efficacy of nearly 50 products against major variants. A subset of products was further evaluated for therapeutic efficacy in hamsters. Here we report results of the hamster studies, including pathogenicity with multiple variants, neutralization capacity of products, and efficacy testing of products against Delta and Omicron variants. These studies demonstrate the loss of efficacy of early products with variant emergence and support the use of the hamster model for evaluating therapeutics.
严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的出现和 2019 冠状病毒病(COVID-19)大流行的爆发导致了对治疗方法的迫切需求。当传统抗病毒药物不可用时,治疗性抗体被开发出来以填补空白。2020 年底,美国政府努力在病毒中和测定和 SARS-CoV-2 感染的仓鼠模型中比较候选治疗性抗体。随着 SARS-CoV-2 变体的出现,该努力扩大到评估近 50 种产品对主要变体的疗效。一部分产品进一步在仓鼠中评估治疗功效。在这里,我们报告仓鼠研究的结果,包括多种变体的致病性、产品的中和能力以及产品对 Delta 和 Omicron 变体的疗效测试。这些研究表明,随着变体的出现,早期产品的疗效丧失,并支持使用仓鼠模型来评估治疗方法。