Constitutive Augmentation of Heat Shock Response in a Producer Cell for Viral Vaccines

Highly attenuated poxviruses are very promising vectors for protective and therapeutic vaccines. They do not replicate in human recipients providing an extremely safe and yet very strong immune stimulation against the vectored antigen. However, because they have to be given at very high doses for full efficacy but are difficult to produce improved cellular substrates for these viruses are urgently needed. We have further improved yields for modified vaccinia Ankara, one of the highly attenuated poxviruses, via expression of a gene from unrelated adenovirus in the AGE1.CR avian designer cell line. We speculate that this factor specifically and constitutively activates beneficial heat shock responses in the host cell allowing production of MVA in suspension cultures to titers close to 109 pfu/mL in a scalable, chemically defined process.