Scholars@Duke publication: Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody.

Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody.

Publication , Journal Article

Rappazzo, CG; Tse, LV; Kaku, CI; Wrapp, D; Sakharkar, M; Huang, D; Deveau, LM; Yockachonis, TJ; Herbert, AS; Battles, MB; O'Brien, CM; Belk, J ...

Published in: Science (New York, N.Y.)

February 2021

Published version (DOI)

The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. We employed a directed evolution approach to engineer three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains and neutralizes representative epidemic sarbecoviruses with high potency. Structural and biochemical studies demonstrate that ADG-2 employs a distinct angle of approach to recognize a highly conserved epitope that overlaps the receptor binding site. In immunocompetent mouse models of SARS and COVID-19, prophylactic administration of ADG-2 provided complete protection against respiratory burden, viral replication in the lungs, and lung pathology. Altogether, ADG-2 represents a promising broad-spectrum therapeutic candidate against clade 1 sarbecoviruses.

Duke Scholars

Author Daniel Wrapp Medicine, Duke Human Vaccine Institute

Published In

Science (New York, N.Y.)

DOI

10.1126/science.abf4830

EISSN

1095-9203

ISSN

0036-8075

Publication Date

February 2021

Volume

371

Issue

6531

Start / End Page

823 / 829

Related Subject Headings

Spike Glycoprotein, Coronavirus
Severe acute respiratory syndrome-related coronavirus
Severe Acute Respiratory Syndrome
SARS-CoV-2
Receptors, Coronavirus
Protein Engineering
Protein Domains
Mice, Inbred BALB C
Mice
Immunoglobulin Fc Fragments

Citation

APA

Chicago

ICMJE

MLA

NLM

Rappazzo, C. G., Tse, L. V., Kaku, C. I., Wrapp, D., Sakharkar, M., Huang, D., … Walker, L. M. (2021). Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody. Science (New York, N.Y.), 371(6531), 823–829. https://doi.org/10.1126/science.abf4830

Rappazzo, C Garrett, Longping V. Tse, Chengzi I. Kaku, Daniel Wrapp, Mrunal Sakharkar, Deli Huang, Laura M. Deveau, et al. “Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody.” Science (New York, N.Y.) 371, no. 6531 (February 2021): 823–29. https://doi.org/10.1126/science.abf4830.

Rappazzo CG, Tse LV, Kaku CI, Wrapp D, Sakharkar M, Huang D, et al. Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody. Science (New York, NY). 2021 Feb;371(6531):823–9.

Rappazzo, C. Garrett, et al. “Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody.” Science (New York, N.Y.), vol. 371, no. 6531, Feb. 2021, pp. 823–29. Epmc, doi:10.1126/science.abf4830.

Rappazzo CG, Tse LV, Kaku CI, Wrapp D, Sakharkar M, Huang D, Deveau LM, Yockachonis TJ, Herbert AS, Battles MB, O’Brien CM, Brown ME, Geoghegan JC, Belk J, Peng L, Yang L, Hou Y, Scobey TD, Burton DR, Nemazee D, Dye JM, Voss JE, Gunn BM, McLellan JS, Baric RS, Gralinski LE, Walker LM. Broad and potent activity against SARS-like viruses by an engineered human monoclonal antibody. Science (New York, NY). 2021 Feb;371(6531):823–829.

Published In

Science (New York, N.Y.)

DOI

10.1126/science.abf4830

EISSN

1095-9203

ISSN

0036-8075

Publication Date

February 2021

Volume

371

Issue

6531

Start / End Page

823 / 829

Related Subject Headings

Spike Glycoprotein, Coronavirus
Severe acute respiratory syndrome-related coronavirus
Severe Acute Respiratory Syndrome
SARS-CoV-2
Receptors, Coronavirus
Protein Engineering
Protein Domains
Mice, Inbred BALB C
Mice
Immunoglobulin Fc Fragments