Monoclonal antibody protects mice against infection and disease when given either before or up to 24 h after airborne challenge with virulent Venezuelan equine encephalitis virus.
Airborne infection with Venezuelan equine encephalitis virus (VEEV) is a significant hazard for laboratory workers, who may not be immunised against VEEV infection as there is no vaccine currently available suitable for human use. We describe a potential alternative strategy that could protect workers exposed to VEEV or similar viruses. VEEV-specific murine monoclonal antibodies (MAB), given by intraperitoneal (i.p.) injection to mice as a single dose of 100 microg, have a half-life of 6-10 days in serum and spread by transudation to respiratory secretions. Administration of MAB (approximately 4 mg/kg) to mice 24h before challenge with approximately 100LD50 of virulent VEEV protected up to 100% animals. The same dose of MAB delivered up to 24h after challenge protected approximately 50%. Two MAB that were synergistic in vitro in plaque reduction neutralisation tests were not synergistic in vivo in protection assays. An examination of virus multiplication, in the blood and internal organs (brain, spleen, lung) of MAB-treated mice infected by the airborne route with VEEV, suggested that therapeutic activity depended both upon the prevention of virus infection of the brain, and the rapid clearance of virus from the periphery. Antiviral therapy with VEEV-specific human or "humanised" MAB, providing that they are administered early, may offer an alternative means of specific medical intervention for those with a known exposure to VEEV.
Phillpotts
R J
RJ
Dstl, Medical Sciences Department, Porton Down, Wiltshire SP4 0JQ, UK.
Jones
L D
LD
Howard
S C
SC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000494:pharmacology*; D000914:Antibodies, Viral / Q000378:metabolism / Q000494:pharmacology*; D004666:Encephalitis Virus, Venezuelan Equine / Q000276:immunology* / Q000472:pathogenicity; D004685:Encephalomyelitis, Venezuelan Equine / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D017056:Medical Laboratory Personnel; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D009784:Occupational Diseases / Q000276:immunology / Q000517:prevention & control; D015047:Zoonoses
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral