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

Theron Gilliland; Matthew Dunn; Yanan Liu; Maria D H Alcorn; Yutaka Terada; Shauna Vasilatos; Jeneveve Lundy; Rong Li; Sham Nambulli; Deanna Larson; Paul Duprex; Hua Wu; Thomas Luke; Christoph Bausch; Kristi Egland; Eddie Sullivan; Zhongde Wang; William B Klimstra

doi:10.1016/j.isci.2023.107764

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

iScience. 2023 Aug 29;26(10):107764. doi: 10.1016/j.isci.2023.107764. eCollection 2023 Oct 20.

Authors

Theron Gilliland¹, Matthew Dunn¹, Yanan Liu², Maria D H Alcorn¹, Yutaka Terada¹, Shauna Vasilatos¹, Jeneveve Lundy¹, Rong Li², Sham Nambulli³, Deanna Larson², Paul Duprex³, Hua Wu⁴, Thomas Luke⁴, Christoph Bausch⁴, Kristi Egland⁴, Eddie Sullivan⁴, Zhongde Wang², William B Klimstra¹

Affiliations

¹ Center for Vaccine Research and Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
² Department of Animal Dairy, Veterinary Sciences, Utah State University, Logan, UT 84341, USA.
³ Center for Vaccine Research and Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15261, USA.
⁴ SAb Biotherapeutics, Inc, Sioux Falls, SD 57104, USA.

Abstract

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.

Keywords: Immune response; Immunology; Virology.