A Potent Recombinant Polyclonal Antibody Therapeutic for Protection Against New SARS-CoV-2 Variants of Concern

Emerging variants of SARS-CoV-2 possess mutations that prevent antibody therapeutics from maintaining anti-viral binding and neutralizing efficacy. Monoclonal antibodies (mAb) shown to neutralize Wuhan-Hu-1 SARS-CoV-2 (ancestral) strain have reduced potency against newer variants. Plasma derived polyclonal hyperimmune drugs have improved neutralization breadth compared to mAbs, but lower titers against SARS-CoV-2 require higher dosages for treatment. We previously developed a highly diverse, recombinant polyclonal antibody therapeutic anti-SARS-CoV-2 immunoglobulin hyperimmune (rCIG). Compared to plasma-derived standard (NIBSC-20/130) or mAb SAD-S35, rCIG has improved neutralization of SARS-CoV-2 across World Health Organization (WHO) variants; however, its potency was reduced against some variants relative to ancestral, in particular omicron. Omicron-specific antibody sequences were enriched from yeast expressing rCIG-scFv antibodies and exhibited increased binding and neutralization to omicron BA.2 while maintaining binding and neutralization to the ancestral strain. Polyclonal antibody libraries such as rCIG can be utilized to develop antibody therapeutics against present and future SARS-CoV-2 threats.