Nature Medicine10, 871 - 875 (2004)
Published online: 11 July 2004; | doi:10.1038/nm1080
An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus
Elisabetta Traggiai1, 6, Stephan Becker2, 6, Kanta Subbarao3, 6, Larissa Kolesnikova2, Yasushi Uematsu4, Maria Rita Gismondo5, Brian R Murphy3, Rino Rappuoli4
& Antonio Lanzavecchia1
1
Institute for Research in Biomedicine, Via Vela 6, CH 6500 Belllinzona, Switzerland.
2
Institut für Virologie, Robert-Koch-Str. 17, D-35037 Marburg, Germany.
3
Laboratory of Infectious Diseases, NIAID/NIH, 50 South Drive, Bethesda, Maryland 20892-8007, USA.
4
Chiron Vaccines, Via Fiorentina 1, I-53100 Siena, Italy.
5
Istituto di Microbiologia, Ospedale Luigi Sacco, Via Grassi 74, I-20175 Milano, Italy.
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 10-8M to 10-11M. 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.
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