Genetically Engineered Viruses as Vaccines -
Although in the past attenuated strains of vaccinia virus were obtained by serial virus passage, have been used for this purpose in 1980's and 1990's Deletion of several genes (thymidine kinase, a growth factor, hemagglutinin, 13.8 kD secreted protein, and ribonucleotide reductase) decreases its virulence.

Similarly insertion of some lymphokine genes (e.g. interleukin-2 or IL-2) also lead to decreased virulence. While reducing virulence or pathogenicity, immune response of the recombinant protein (coded by gene inserted in the virus for developing specific vaccine) must be increased.

More than one gene can also be stably integrated into attenuated vaccinia virus for developing recombinant virus to be used as a vaccine against multiple pathogens.

A glycoprotein gene of rabies virus has been integrated and the resulting rabies virus vaccine has been field tested in Europe and U.S.A. giving promising results.

Other vaccines against HIV are being developed using the gene for HIV-1 envelope glycoprotein. In future, the widespread use of Vaccinia as a live vaccine will depend on improving safety, while achieving higher response to the recombinant protein.