The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients.
Lakshmanane Premkumar,Bruno Segovia-Chumbez,Ramesh Jadi,David R. Martinez,Rajendra Raut,Alena J. Markmann,Caleb Cornaby,Luther A. Bartelt,Susan R. Weiss,Yara A. Park,Caitlin E. Edwards,Eric T. Weimer,Erin M. Scherer,Nadine Rouphael,Srilatha Edupuganti,Daniela Weiskopf,Longping V. Tse,Yixuan J. Hou,David M. Margolis,Alessandro Sette,Alessandro Sette,Matthew H. Collins,John L. Schmitz,Ralph S. Baric,Aravinda M. de Silva +24 more
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Results, which reveal the early kinetics of Sars-CoV-2 antibody responses, support using the RBD antigen in serological diagnostic assays and RBD-specific antibody levels as a correlate of SARS-Co V-2 neutralizing antibodies in people.Abstract:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first emerged in late 2019 is responsible for a pandemic of severe respiratory illness. People infected with this highly contagious virus can present with clinically inapparent, mild, or severe disease. Currently, the virus infection in individuals and at the population level is being monitored by PCR testing of symptomatic patients for the presence of viral RNA. There is an urgent need for SARS-CoV-2 serologic tests to identify all infected individuals, irrespective of clinical symptoms, to conduct surveillance and implement strategies to contain spread. As the receptor binding domain (RBD) of the spike protein is poorly conserved between SARS-CoVs and other pathogenic human coronaviruses, the RBD represents a promising antigen for detecting CoV-specific antibodies in people. Here we use a large panel of human sera (63 SARS-CoV-2 patients and 71 control subjects) and hyperimmune sera from animals exposed to zoonotic CoVs to evaluate RBD's performance as an antigen for reliable detection of SARS-CoV-2-specific antibodies. By day 9 after the onset of symptoms, the recombinant SARS-CoV-2 RBD antigen was highly sensitive (98%) and specific (100%) for antibodies induced by SARS-CoVs. We observed a strong correlation between levels of RBD binding antibodies and SARS-CoV-2 neutralizing antibodies in patients. Our results, which reveal the early kinetics of SARS-CoV-2 antibody responses, support using the RBD antigen in serological diagnostic assays and RBD-specific antibody levels as a correlate of SARS-CoV-2 neutralizing antibodies in people.read more
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Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding.
Tyler N. Starr,Allison J. Greaney,Allison J. Greaney,Sarah K Hilton,Sarah K Hilton,Daniel Ellis,Katharine H.D. Crawford,Katharine H.D. Crawford,Adam S. Dingens,Mary Jane Navarro,John E. Bowen,M. Alejandra Tortorici,Alexandra C. Walls,Neil P. King,David Veesler,Jesse D. Bloom,Jesse D. Bloom,Jesse D. Bloom +17 more
TL;DR: It is found that a substantial number of mutations to the RBD are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses.
Journal ArticleDOI
Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity.
Carolyn Rydyznski Moderbacher,Sydney I. Ramirez,Sydney I. Ramirez,Jennifer M. Dan,Jennifer M. Dan,Alba Grifoni,Kathryn M. Hastie,Daniela Weiskopf,Simon Bélanger,Robert K. Abbott,Christina K. Kim,Jinyong Choi,Yu Kato,Eleanor G. Crotty,Cheryl Kim,Stephen A. Rawlings,Jose Mateus,Longping V. Tse,April Frazier,Ralph S. Baric,Bjoern Peters,Jason A. Greenbaum,Erica Ollmann Saphire,Erica Ollmann Saphire,Davey M. Smith,Alessandro Sette,Alessandro Sette,Shane Crotty,Shane Crotty +28 more
TL;DR: A combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4+ and CD8+ T cell and neutralizing antibody responses in acute and convalescent subjects suggested roles for both CD4 plus T cells in protective immunity in COVID-19.
Journal ArticleDOI
Adaptive immunity to SARS-CoV-2 and COVID-19.
TL;DR: In this article, a picture has begun to emerge that reveals that CD4+ T cells, CD8+ Tcells, and neutralizing antibodies all contribute to control SARS-CoV-2 in both non-hospitalized and hospitalized cases of COVID-19.
Journal ArticleDOI
A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein-protein interaction.
Chee Wah Tan,Wan Ni Chia,Xijian Qin,Pei Liu,Mark I-Cheng Chen,Charles Tiu,Zhiliang Hu,Zhiliang Hu,Vivian Chih Wei Chen,Barnaby Edward Young,Barnaby Edward Young,Wan Rong Sia,Yee-Joo Tan,Yee-Joo Tan,Randy Foo,Yongxiang Yi,David C. Lye,Danielle E. Anderson,Lin-Fa Wang +18 more
TL;DR: A blocking assay based on the recombinant receptor-binding domain of SARS-CoV-2 spike protein and human angiotensin-converting enzyme 2 receptor provides an alternative to conventional antibody neutralization assays requiring live virus.
Journal ArticleDOI
Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans.
Jose Mateus,Alba Grifoni,Alison Tarke,John Sidney,Sydney I. Ramirez,Sydney I. Ramirez,Jennifer M. Dan,Jennifer M. Dan,Zoe C Burger,Stephen A. Rawlings,Davey M. Smith,Elizabeth J. Phillips,Simon Mallal,Marshall Lammers,Paul Rubiro,Lorenzo Quiambao,Aaron Sutherland,Esther Dawen Yu,Ricardo da Silva Antunes,Jason A. Greenbaum,April Frazier,Alena J. Markmann,Lakshmanane Premkumar,Aravinda M. de Silva,Bjoern Peters,Bjoern Peters,Shane Crotty,Shane Crotty,Alessandro Sette,Alessandro Sette,Daniela Weiskopf +30 more
TL;DR: A range of preexisting memory CD4+ T cells that are cross-reactive with comparable affinity to SARS-CoV-2 and the common cold coronaviruses human coronavirus (HCoV)-OC43, H coV-229E, H CoV-NL63, and HCov-HKU1 are demonstrated.
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TL;DR: A rapid and simple point‐of‐care lateral flow immunoassay that can detect immunoglobulin M (IgM) and IgG antibodies simultaneously against SARS‐CoV‐2 virus in human blood within 15 minutes which can detect patients at different infection stages is developed.
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