Gilliland Theron, Dunn Matthew, Liu Yanan, Alcorn Maria D H, Terada Yutaka, Vasilatos Shauna, Lundy Jeneveve, Li Rong, Nambulli Sham, Larson Deanna, Duprex Paul, Wu Hua, Luke Thomas, Bausch Christoph, Egland Kristi, Sullivan Eddie, Wang Zhongde, Klimstra William B
Center for Vaccine Research and Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Department of Animal Dairy, Veterinary Sciences, Utah State University, Logan, UT 84341, USA.
iScience. 2023 Aug 29;26(10):107764. doi: 10.1016/j.isci.2023.107764. eCollection 2023 Oct 20.
Pandemic SARS-CoV-2 has undergone rapid evolution resulting in the emergence of many variants with mutations in the spike protein, some of which appear to evade antibody neutralization, transmit more efficiently, and/or exhibit altered virulence. This raises significant concerns regarding the efficacy of anti-S monoclonal antibody-based therapeutics which have failed against variant SARS-CoV-2 viruses. To address this concern, SAB-185, a human anti-SARS-CoV-2 polyclonal antibody was generated in the DiversitAb platform. SAB-185 exhibited equivalent, robust neutralization for Munich, Alpha, Beta, Gamma, and Δ144-146 variants and, although diminished, retained PRNT and PRNT neutralization endpoints for Delta and Omicron variants. Human ACE2 transgenic Syrian hamsters, which exhibit lethal SARS-CoV-2 disease, were protected from mortality after challenge with the Munich, Alpha, Beta, Delta, and Δ144-146 variants and clinical signs after non-lethal Omicron BA.1 infection. This suggests that SAB-185 may be an effective immunotherapy even in the presence of ongoing viral mutation.
大流行的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）经历了快速进化，导致出现了许多刺突蛋白发生突变的变体，其中一些变体似乎能够逃避抗体中和、更有效地传播和/或表现出改变的毒力。这引发了人们对基于抗S单克隆抗体的治疗方法疗效的重大担忧，这些治疗方法对SARS-CoV-2病毒变体无效。为了解决这一担忧，在DiversitAb平台上产生了一种人抗SARS-CoV-2多克隆抗体SAB-185。SAB-185对慕尼黑、阿尔法、贝塔、伽马和Δ144-146变体表现出同等强大的中和作用，并且尽管中和作用有所减弱，但对德尔塔和奥密克戎变体仍保留了蚀斑减少中和试验（PRNT）中和终点。人血管紧张素转换酶2（ACE2）转基因叙利亚仓鼠会出现致死性SARS-CoV-2疾病，在用慕尼黑、阿尔法、贝塔、德尔塔和Δ144-146变体攻击后可免受死亡，在非致死性奥密克戎BA.1感染后可免受临床症状影响。这表明即使在病毒持续突变的情况下，SAB-185也可能是一种有效的免疫疗法。
