Modified vaccinia virus Ankara (MVA) is a highly attenuated vaccinia virus that 
is under consideration as an alternative to the conventional smallpox vaccine 
Dryvax. MVA was attenuated by extensive passage of vaccinia virus Ankara in 
chicken embryo fibroblasts. Several immunomodulatory genes and genes that 
influence host range are deleted or mutated, and replication is aborted in the 
late stage of infection in most nonavian cells. The effect of these mutations on 
immunogenicity is not well understood. Since the structural genes appear to be 
intact in MVA, it is hypothesized that critical targets for antibody 
neutralization have been retained. To test this, we probed microarrays of the 
Western Reserve (WR) proteome with sera from humans and macaques after MVA and 
Dryvax vaccination. As most protein sequences of MVA are 97 to 99% identical to 
those of other vaccinia virus strains, extensive binding cross-reactivity is 
expected, except for those deleted or truncated. Despite different hosts and 
immunization regimens, the MVA and Dryvax antibody profiles were broadly 
similar, with antibodies against membrane and core proteins being the best 
conserved. The responses to nonstructural proteins were less well conserved, 
although these are not expected to influence virus neutralization. The broadest 
antibody response was obtained for hyperimmune rabbits with WR, which is 
pathogenic in rabbits. These data indicate that, despite the mutations and 
deletions in MVA, its overall immunogenicity is broadly comparable to that of 
Dryvax, particularly at the level of antibodies to membrane proteins. The work 
supports other information suggesting that MVA may be a useful alternative to 
Dryvax.