Vaccinia virus recombinants encoding the truncated structural gene region of Venezuelan equine encephalitis virus (VEEV) give solid protection against peripheral challenge but only partial protection against airborne challenge with virulent VEEV

Vaccinia virus (VV) recombinants that contain the genes encoding the Venezu elian equine encephalitis virus (VEEV) structural gene region (C-E3-E2-5 K- EI) solidly protect mice against peripheral challenge with virulent VEEV, b ut provide only partial protection against airborne challenge. To improve u pon these results we focussed on the principal antigens involved in protect ion. VV recombinants encoding the structural genes E3-E2-6 K-E1, E3-E2-6 K or 6 K-E1 were prepared and evaluated for their ability to protect Balb/c m ice after a single dorsal scarification with 10(8) PFU against peripheral o r airborne challenge with virulent VEEV: The antibody response was also exa mined. Our experiments provide new evidence that truncates of the VEEV stru ctural region (E3-E2-6 K-EI, E3-E2-6 K), cloned and expressed in VV, protec t against challenge with virulent virus. They also confirm the important ro le of E2 in protection. However, we were unable to improve upon previously reported levels of protection against airborne challenge. A substantial lev el of circulating antibodies and the presence of local IgA (not always indu ced by mucosal immunization) (Greenway ei al., 1992) appear essential for p rotection against the airborne virus. Current VV-VEEV recombinants seem una ble to elicit this level of immune response and further improvements are th erefore required to increase the immunogenicity of VV-VEEV vaccines.