Modified vaccinia Ankara strains with identical coding sequences actually represent complex mixtures of viruses that determine the biological properties of each strain

Modified vaccinia Ankara (MVA) was developed by serial passages on chicken embryo fibroblast cells. After passage 570, the virus was considered homogenous and genetically stable. Three MVA strains (MVA-572, MVA-1721 and MVA-BN (R)) have been analyzed and shown to be 100% genetically identical; although significant differences in their phenotypes were illustrated. All MVA strains except MVA-BN (R) replicated in human cells, or killed immune suppressed mice. Viruses isolated from dead animals were shown to represent variants present within MVA-572 or MVA-1721 used to inoculate the mice. These subpopulations were shown to encode mutations, or contain less than the six deletions associated with MVA and had significantly altered phenotypes compared to the parental MVA strains. MVA is a complex polyclonal mixture of viruses, the composition of which governs the phenotype. (C) 2009 Elsevier Ltd. All rights reserved.