Reshaping a human monoclonal antibody to inhibit human respiratory syncytial virus infection in vivo.
We transferred the complementarity determining regions from a murine monoclonal antibody that neutralizes infection by respiratory syncytial virus (RSV) to a human IgG1 monoclonal antibody. The resulting reshaped human antibody lost affinity for RSV, but an additional alteration to one of the framework regions restored binding affinity and specificity. This second generation reshaped human monoclonal antibody cross-reacted with all clinical isolates of RSV tested and both prevented disease and cured mice even when administered four days after infection. We expect the antibody will prove useful in the management of this major childhood disease.
Tempest
P R
PR
Scotgen Limited, Aberdeen, Scotland, UK.
Bremner
P
P
Lambert
M
M
Taylor
G
G
Furze
J M
JM
Carr
F J
FJ
Harris
W J
WJ
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D000956:Antigens, Viral / Q000276:immunology; D003001:Cloning, Molecular / Q000379:methods; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D010253:Respirovirus Infections / Q000517:prevention & control* / Q000628:therapy
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region