chapter  3
Recombination-Mediated Genetic Engineering of a Bacterial Artificial Chromosome Clone of Modified Vaccinia Virus Ankara (MVA)
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Introduction Modied Vaccinia virus Ankara (MVA) is a replication-decient attenuated poxvirus that was derived from Vaccinia virus by Mayr et al. through more than 500 blind passages in chick embryo broblast (CEF) cell culture [1]. With the notable exception of the Syrian hamster cell line BHK-21 [2], MVA is unable to replicate productively in mammalian cells, though genome replication, late gene expression and immature virion formation usually occur [3], [4]. During its attenuation, MVA acquired large genomic deletions totalling about 30 kb, resulting in the complete loss of 26 open reading frames (ORFs), together with truncation or fragmentation of a further 21 ORFs and numerous smaller scale mutations [5]. MVA does not therefore express many of the known poxviral immune evasion and virulence factors [6]–[8], though how this determines its abortive phenotype in mammalian cells is not well understood [9]. Despite these features, MVA is at

least as immunogenic as conventional replicating Vaccinia virus [10]–[13] and has the advantage of a considerably improved safety prole [14].