title: A humanised murine monoclonal antibody protects mice from Venezuelan equine encephalitis virus, Everglades virus and Mucambo virus when administered up to 48 h after airborne challenge.
abstract: Currently there are no licensed antiviral treatments for the Alphaviruses Venezuelan equine encephalitis virus (VEEV), Everglades virus and Mucambo virus. We previously developed a humanised version of the mouse monoclonal antibody 1A3B-7 (Hu1A3B-7) which exhibited a wide range of reactivity in vitro and was able to protect mice from infection with VEEV. Continued work with the humanised antibody has now demonstrated that it has the potential to be a new human therapeutic. Hu1A3B-7 successfully protected mice from infection with multiple Alphaviruses. The effectiveness of the humanisation process was determined by assessing proliferation responses in human T-cells to peptides derived from the murine and humanised versions of the V(H) and V(L) domains. This analysis showed that the number of human T-cell epitopes within the humanised antibody had been substantially reduced, indicating that Hu1A3B-7 may have reduced immunogenicity in vivo.
authors.affiliation: Biomedical Sciences Department, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK. lmobrien@dstl.gov.uk
authors.forename: Lyn M
authors.initials: LM
authors.lastname: O'Brien
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Goodchild
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Phillpotts
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Perkins
mesh_terms: D000391:Air Microbiology; D000524:Alphavirus / Q000276:immunology*; D018354:Alphavirus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D000595:Amino Acid Sequence; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D004666:Encephalitis Virus, Venezuelan Equine / Q000276:immunology*; D004685:Encephalomyelitis, Venezuelan Equine / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006801:Humans; D007116:Immunization, Passive; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral