Modified vaccinia virus Ankara undergoes limited replication in human cells and lacks several immunomodulatory proteins: implications for use as a human vaccine.
Modified virus Ankara (MVA) is a vaccinia virus (VV) strain that was attenuated by serial passage through chick embryo fibroblasts (CEFs) and contains six large genomic deletions compared with parental virus. MVA replicates well in CEFs, but poorly in most mammalian cells. Recombinant MVA is a promising human vaccine candidate due to its restricted host range, immunogenicity and avirulence in animal models, and excellent safety record as a smallpox vaccine. Here we present a further characterization of MVA and demonstrate that: (i) MVA can replicate, albeit poorly, in transformed human cell lines, but not in primary human fibroblasts although there is limited cell-to-cell spread; (ii) MVA is a potent inducer of type I interferon (IFN) from primary human cells, which may restrict virus spread in vivo; and (iii) unlike other VV strains, MVA does not express soluble receptors for IFN-gamma, IFN-alpha/beta, tumour necrosis factor and CC chemokines, but does express a soluble interleukin-1beta receptor. This provides a plausible and testable explanation for the good immunogenicity of MVA despite its poor replication in mammals. The implications of these findings for the use of MVA as a safe and immunogenic human vaccine candidate are discussed.
Blanchard
T J
TJ
Sir William Dunn School of Pathology, University of Oxford, UK.
Alcami
A
A
Andrea
P
P
Smith
G L
GL
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D007370:Interferon Type I / Q000276:immunology; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D011817:Rabbits; D053633:Receptor, Interferon alpha-beta; D018121:Receptors, Cytokine / Q000378:metabolism*; D017471:Receptors, Interferon / Q000378:metabolism; D014616:Vaccinia virus / Q000276:immunology* / Q000378:metabolism / Q000502:physiology*; D014765:Viral Vaccines; D014779:Virus Replication; D000096743:Interferon gamma Receptor
D007370:Interferon Type I; D008565:Membrane Proteins; D053633:Receptor, Interferon alpha-beta; D018121:Receptors, Cytokine; D017471:Receptors, Interferon; D014765:Viral Vaccines; D000096743:Interferon gamma Receptor