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PMID: 15247913 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus.

Nature medicine ·Vol. 10 ·No. 8 ·2004-08-00 ·Pages 871-5

Traggiai E, Becker S, Subbarao K, Kolesnikova L, Uematsu Y, Gismondo MR, Murphy BR, Rappuoli R, Lanzavecchia A

Abstract

Passive serotherapy can confer immediate protection against microbial infection, but methods to rapidly generate human neutralizing monoclonal antibodies are not yet available. We have developed an improved method for Epstein-Barr virus transformation of human B cells. We used this method to analyze the memory repertoire of a patient who recovered from severe acute respiratory syndrome coronavirus (SARS-CoV) infection and to isolate monoclonal antibodies specific for different viral proteins, including 35 antibodies with in vitro neutralizing activity ranging from 10(-8)M to 10(-11)M. One such antibody confers protection in vivo in a mouse model of SARS-CoV infection. These results show that it is possible to interrogate the memory repertoire of immune donors to rapidly and efficiently isolate neutralizing antibodies that have been selected in the course of natural infection.

MeSH Terms
Adult Animals Antibodies, Monoclonal/isolation & purification B-Lymphocytes/immunology Chlorocebus aethiops DNA Primers Disease Models, Animal Enzyme-Linked Immunosorbent Assay Herpesvirus 4, Human/metabolism Humans Immunization, Passive/methods Immunologic Memory/immunology Membrane Glycoproteins/genetics,metabolism Mice Microscopy, Immunoelectron Neutralization Tests Polymerase Chain Reaction Severe Acute Respiratory Syndrome/immunology Spike Glycoprotein, Coronavirus Transformation, Genetic Vero Cells Viral Envelope Proteins/genetics,metabolism alpha-Macroglobulins/metabolism
Chemicals
Antibodies, Monoclonal DNA Primers Membrane Glycoproteins Spike Glycoprotein, Coronavirus Viral Envelope Proteins alpha-Macroglobulins polyclonal B cell activator spike glycoprotein, SARS-CoV
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Traggiai Elisabetta
Institute for Research in Biomedicine, Via Vela 6, CH 6500 Belllinzona, Switzerland.
Becker Stephan
Subbarao Kanta
Kolesnikova Larissa
Uematsu Yasushi
Gismondo Maria Rita
Murphy Brian R
Rappuoli Rino
Lanzavecchia Antonio
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Article Info
Journal
Nature medicine
Abbr.
Nat Med
ISSN
1078-8956
DOI
10.1038/nm1080
Published
2004-08-00
Epub
2004-00-11
Pages
871-5
Language
English
Region
United States
NLM ID
9502015
PMCID
PMC7095806
Subset
IM
External Links
PubMed source DOI: 10.1038/nm1080 PMC Full Text View journal details
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