Transchromosomic bovine-derived anti-SARS-CoV-2 polyclonal human antibodies protects hACE2 transgenic hamsters against multiple variants

• Published in: iScience Vol. 26; no. 10; p. 107764
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.10.2023; Elsevier
• Subjects: Immune response; Immunology; Virology; Immunology; Immune response; Virology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.107764

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 in vitro neutralization for Munich, Alpha, Beta, Gamma, and Δ144-146 variants and, although diminished, retained PRNT50 and PRNT80 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. [Display omitted] •A transchromosomic bovine polyclonal antibody neutralizes variants of SARS-CoV-2•We use a novel human ACE2 (hACE2) transgenic hamster model of SARS-CoV-2 infection•The polyclonal antibody protects hACE2 hamsters from all variants tested•Hyperimmunization of the bovines may promote protection against SARS-CoV-2 variants Immunology; Immune response; Virology