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PMID: 15488951 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Molecular characterization of a panel of murine monoclonal antibodies specific for the SARS-coronavirus.

Molecular immunology ·Vol. 42 ·No. 1 ·2005-01-00 ·Pages 125-36

Gubbins MJ, Plummer FA, Yuan XY, Johnstone D, Drebot M, Andonova M, Andonov A, Berry JD

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 0.075 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 V(H)-gene alleles. For instance, one evident trend is high sequence conservation in the V(H) 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.

MeSH Terms
Amino Acid Sequence Animals Antibodies, Monoclonal/biosynthesis Antibody Specificity Evolution, Molecular Hybridomas Immunoglobulin Heavy Chains/genetics Immunoglobulin Light Chains/genetics Mice Molecular Sequence Data Neutralization Tests SARS Virus/immunology
Chemicals
Antibodies, Monoclonal Immunoglobulin Heavy Chains Immunoglobulin Light Chains
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Gubbins Michael J
National Microbiology Laboratory, Health Canada, 1015 Arlington Street, Winnipeg, Man., Canada R3E 3R2.
Plummer Frank A
Yuan Xin Y
Johnstone Darrell
Drebot Mike
Andonova Maya
Andonov Anton
Berry Jody D
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Article Info
Journal
Molecular immunology
Abbr.
Mol Immunol
ISSN
0161-5890
DOI
10.1016/j.molimm.2004.06.032
Published
2005-01-00
Pages
125-36
Language
English
Region
England
NLM ID
7905289
PMCID
PMC7112650
Subset
IM
Databases
GENBANK
AY605265, AY605266, AY605267, AY605268, AY605269, AY605270, AY605279, AY605280, AY605281, AY605282
External Links
PubMed source DOI: 10.1016/j.molimm.2004.06.032 PMC Full Text View journal details
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