Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9142218 | Molecular Immunology | 2005 | 12 Pages |
Abstract
The availability of monoclonal antibodies (mAbs) specific for the SARS-coronavirus (SARS-CoV) is important for the development of both diagnostic tools and treatment of infection. A molecular characterization of nine monoclonal antibodies raised in immune mice, using highly purified, inactivated SARS-CoV as the inoculating antigen, is presented in this report. These antibodies are specific for numerous viral protein targets, and six of them are able to effectively neutralize SARS-CoV in vitro, including one with a neutralizing titre of 0.075Â nM. A phylogenetic analysis of the heavy and light chain sequences reveals that the mAbs share considerable homology. The majority of the heavy chains belong to a single Ig germline V-gene family, while considerably more sequence variation is evident in the light chain sequences. These analyses demonstrate that neutralization ability can be correlated with specific murine VH-gene alleles. For instance, one evident trend is high sequence conservation in the VH chains of the neutralizing mAbs, particularly in CDR-1 and CDR-2. The results suggest that optimization of murine mAbs for neutralization of SARS-CoV infection will likely be possible, and will aid in the development of diagnostic tools and passive treatments for SARS-CoV infection.
Keywords
i.p.variable region heavy chainSARS-coronavirusFreund’s Complete Adjuvants.c.PBSCDRCOVMonoclonal antibodyimmunoglobulin Immunogeneticsphylogenetic analysisDiversityNeutralizingintraperitonealsubcutaneousSARSsevere acute respiratory syndromePhosphate buffered salinecomplementarity determining regionJoiningFrameworkmurineCoronavirus
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Authors
Michael J. Gubbins, Frank A. Plummer, Xin Y. Yuan, Darrell Johnstone, Mike Drebot, Maya Andonova, Anton Andonov, Jody D. Berry,