Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with amino-acid substitutions and deletions in spike protein (S) can reduce the effectiveness of monoclonal antibodies (mAbs) and may compromise immunity induced by vaccines. We report a polyclonal, fully human, anti-SARS-CoV-2 immunoglobulin produced in transchromosomic bovines (Tc-hIgG-SARS-CoV-2) hyperimmunized with two doses of plasmid DNA encoding the SARS-CoV-2 Wuhan strain S gene, followed by repeated immunization with S protein purified from insect cells. The resulting Tc-hIgG-SARS-CoV-2, termed SAB-185, efficiently neutralizes SARS-CoV-2, and vesicular stomatitis virus (VSV) SARS-CoV-2 chimeras in vitro . Neutralization potency was retained for S variants including S477N, E484K, and N501Y, substitutions present in recent variants of concern. In contrast to the ease of selection of escape variants with mAbs and convalescent human plasma, we were unable to isolate VSV-SARS-CoV-2 mutants resistant to Tc-hIgG-SARS-CoV-2 neutralization. This fully human immunoglobulin that potently inhibits SARS-CoV-2 infection may provide an effective therapeutic to combat COVID-19.
Keywords: SARS-cov-2; polyclonal antibodies; transchromosomic bovines; variants.
【저자키워드】 SARS-CoV-2, variants, polyclonal antibodies, transchromosomic bovines, 【초록키워드】 COVID-19, severe acute respiratory syndrome coronavirus 2, coronavirus, Immunity, Vaccines, S protein, neutralization, SARS-COV-2 infection, monoclonal antibody, variant, variants of concern, in vitro, severe acute respiratory syndrome Coronavirus, monoclonal antibodies, anti-SARS-CoV-2, immunization, variants, Spike protein, DNA, Immunoglobulin, VSV, N501Y, therapeutic, Effectiveness, substitutions, Deletion, bovine, E484K, polyclonal antibodies, mutant, respiratory, convalescent, vesicular stomatitis virus, mAbs, mAb, Human plasma, S gene, dose, Plasmid, followed by, vesicular stomatitis, acute respiratory syndrome, acute respiratory syndrome coronavirus, neutralization potency, Substitution, Wuhan strain, amino-acid, stomatitis, deletions, insect cells, S477N, human immunoglobulin, repeated, effective, polyclonal, plasmid DNA, neutralize, anti-SARS-CoV-2 immunoglobulin, produced, resulting, inhibit, reduce, retained, purified, S variant, the SARS-CoV-2, 【제목키워드】 Human, bovine, viral variant, SARS-CoV-2 spike antigen, neutralize,