Development of a Genetically-Engineered Venezuelan Equine Encephalitis Virus Vaccine.

摘要

Infection of equines with epizootic Venezuelan equine encephalitis (VEE) virus frequently results in fever, leukopenia, meningoencephalitis, and death. Histopathologic changes in the hemolymphatic system include wide spread lymphoid necrosis and depletion of hematopoietic cells in the bone marrow. Changes in the CNS correlated with clinical encephalitis and include diffuse meningoencephalitis with perivascular infiltration of leukocytes, and necrosis. We have evaluated the efficacy of a recombinant vaccinia/VEE virus vaccine (TC-5A) to protect horses against challenge with equine virulent VEE virus. Horses immunized with vaccinia/VEE virus recombinant virus developed low titer ELISA and neutralizing antibodies after the first immunization. These animals were reimmunized 92 days after the first immunization with recombinant virus to boost the immune response prior to virus challenge. Serum antibody titers seven days following reimmunization were high, indicating antigenic priming had been accomplished by the initial recombinant virus immunization. Horses immunized with the vaccine/VEE recombinant, wild-type vaccinia virus, and TC-83 vaccine were all challenged with PFu of equine virulent VEE virus. Following challenge animals immunized with wild-type vaccinia virus developed a leukopenia, became viremic, febrile, depressed and were euthanized on the sixth day after challenge. Horses immunized with either TC-83 or vaccina/VEE recombinant viruses did not become viremic or develop clinical or hematologic signs of VEE following challenge. (SDW)