Molecular characterization of a panel of murine monoclonal antibodies specific for the SARS-coronavirus.
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.
Gubbins
Michael J
MJ
National Microbiology Laboratory, Health Canada, 1015 Arlington Street, Winnipeg, Man., Canada R3E 3R2.
Plummer
Frank A
FA
Yuan
Xin Y
XY
Johnstone
Darrell
D
Drebot
Mike
M
Andonova
Maya
M
Andonov
Anton
A
Berry
Jody D
JD
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D000918:Antibody Specificity; D019143:Evolution, Molecular; D006825:Hybridomas; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains