Summary auto-generated
Modified vaccinia virus Ankara (MVA) is a highly attenuated poxvirus with restricted host range that offers excellent safety profiles for vaccine development and recombinant gene expression. However, its propagation has been limited to primary chicken embryo fibroblasts (CEF), which are difficult to maintain. This study screened various mammalian cell lines to identify alternative hosts for MVA production. Researchers infected multiple human transformed cell lines, animal cell lines, and primary human cells with recombinant MVA expressing the lacZ reporter gene. Baby hamster kidney (BHK) cells supported robust MVA replication with kinetics and recombinant protein expression nearly identical to CEF cells, making them a practical alternative for routine virus propagation. In contrast, most other cell lines tested were non-permissive or allowed only minimal viral replication. Importantly, MVA failed to replicate productively in any primary human cell type tested, including fibroblasts, peripheral blood mononuclear cells, monocytes, and dendritic cells, despite allowing efficient recombinant gene expression. These findings significantly enhance MVA's practical utility and safety profile for developing expression vectors and live recombinant vaccines for infectious diseases and cancer therapy.
Key findings
- Baby hamster kidney (BHK) cells support MVA replication and recombinant gene expression comparable to primary chicken embryo fibroblasts, providing an accessible alternative cell line for routine MVA propagation
- MVA replication was blocked in all tested primary human cell types (fibroblasts, PBMC, monocytes, dendritic cells), while recombinant gene expression remained efficient
- Most other mammalian cell lines tested were non-permissive for MVA replication, confirming the virus's restricted host range and enhanced safety profile
- The identification of BHK cells as a suitable production system improves the accessibility and reproducibility of MVA-based vaccine development
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Abstract
Although desirable for safety reasons, the host range restrictions of modified vaccinia virus Ankara (MVA) make it less applicable for general use. Propagation in primary chicken embryo fibroblasts (CEF) requires particular cell culture experience and has no pre-established record of tissue culture reproducibility. We investigated a variety of established cell lines for productive virus growth and recombinant gene expression. Baby hamster kidney cells (BHK), a well-characterized, easily maintained cell line, supported MVA growth and as proficient expression of the E. coli lacZ reporter gene as the highly efficient CEF, whereas other cell lines were non-permissive or allowed only very limited MVA replication. Importantly, no virus production occurred in patient-derived infected primary human cells. These results emphasize the safety and now improved accessibility of MVA for the development of expression vectors and live recombinant vaccines.