A recombinant humanized monoclonal antibody completely protects mice against lethal challenge with Venezuelan equine encephalitis virus.
A recombinant humanized antibody to Venezuelan equine encephalitis virus (VEEV) was constructed in a monocistronic adenoviral expression vector with a foot-and-mouth-disease virus-derived 2A self-cleavage oligopeptide inserted between the antibody heavy and light chains. After expression in mammalian cells, the heavy and light chains of the humanized antibody (hu1A4A1IgG1-2A) were completely cleaved and properly dimerized. The purified hu1A4A1IgG1-2A retained VEEV binding affinity and neutralizing activity similar to its parental murine antibody. The half-life of hu1A4A1IgG1-2A in mice was approximately 2 days. Passive immunization of hu1A4A1IgG1-2A in mice (50 microg/mouse) 24 h before or after virulent VEEV challenge provided complete protection, indicating that hu1A4A1IgG1-2A has potent prophylactic and therapeutic effects against VEEV infection.
Hu
Wei-Gang
WG
Defence Research and Development Canada - Suffield, Medicine Hat, Alberta, Canada T1A 8K6. wei-gang.hu@drdc-rddc.gc.ca
Phelps
Amanda L
AL
Jager
Scott
S
Chau
Damon
D
Hu
Charles C
CC
O'Brien
Lyn M
LM
Perkins
Stuart D
SD
Gates
Amanda J
AJ
Phillpotts
Robert J
RJ
Nagata
Les P
LP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology / Q000627:therapeutic use*; D000918:Antibody Specificity; D002460:Cell Line; D004666:Encephalitis Virus, Venezuelan Equine / Q000276:immunology; D004685:Encephalomyelitis, Venezuelan Equine / Q000517:prevention & control*; D006207:Half-Life; D006801:Humans; D007116:Immunization, Passive; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D014764:Viral Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D014764:Viral Proteins; C057421:virus protein 2A