TY - JOUR
T1 - Human immunoglobulin from transchromosomic bovines hyperimmunized with SARS-CoV-2 spike antigen efficiently neutralizes viral variants
AU - Liu, Zhuoming
AU - Wu, Hua
AU - Egland, Kristi A.
AU - Gilliland, Theron C.
AU - Dunn, Matthew D.
AU - Luke, Thomas C.
AU - Sullivan, Eddie J.
AU - Klimstra, William B.
AU - Bausch, Christoph L.
AU - Whelan, Sean P.J.
N1 - Funding Information:
SAB Biotherapeutics, Inc., is receiving support from the Department of Defense (DoD) Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense (JPEO-CBRND) Joint Project Lead for Enabling Biotechnologies (JPL-EB), and from the Biomedical Advanced Research Development Authority (BARDA), part of the Assistant Secretary for Preparedness and Response (ASPR) at the US. Department of Health and Human Services, to develop SAB-185, a countermeasure to SARS-CoV-2 (Effort sponsored by the US. Government under Other Transaction number W15QKN-16-9-1002 between the Medical CBRN Defense Consortium (MCDC), and the Government). The US Government is authorized to reproduce and distribute reprints for Governmental purposes notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of the US. Government. E.J.S, C.L.B, HW, K.A.E, and T.C.L are employees of SAB Biotherapeutics, Inc. SAB Biotherapeutics, Inc. S.P.J.W and Z.L are employees of Washington University of Saint Louis and conducted this research under a contract with SAB Biotherapeutics, Inc. W.B.K, T.C.G and M.D.D are employees of the University of Pittsburgh and conducted this research under a contract with SAB Biotherapeutics, Inc.
Publisher Copyright:
© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - SARS-cov-2
KW - polyclonal antibodies
KW - transchromosomic bovines
KW - variants
UR - http://www.scopus.com/inward/record.url?scp=85109821154&partnerID=8YFLogxK
U2 - 10.1080/21645515.2021.1940652
DO - 10.1080/21645515.2021.1940652
M3 - Article
C2 - 34228597
AN - SCOPUS:85109821154
SN - 2164-5515
VL - 18
JO - Human Vaccines and Immunotherapeutics
JF - Human Vaccines and Immunotherapeutics
IS - 2
M1 - 1940652
ER -