Modified vaccinia Ankara
The Modified Vaccinia Ankara (MVA) is an attenuated vaccine of a poxvirus. It was licensed and used as a poxvirus vaccine in Bavaria and is a vector for vaccination against non-poxvirus diseases.
Vaccinia viruses re-engineered to express foreign genes are vectors for production of recombinant proteins, the most common being a vaccine delivery system for antigens. Concerns about the safety of the vaccinia virus have been addressed by the development of vectors based on attenuated vaccinia viruses. One of them, the Modified Vaccinia Ankara (MVA') virus, is a highly attenuated strain of vaccinia virus that was developed towards the end of the campaign for the eradication of smallpox by Anton Mayr in Germany. Produced by more than 500 passages of vaccinia virus in chicken cells (chicken embryo fibroblast, MVA has lost about 10% of the vaccinia genome and with it the ability to replicate efficiently in primate cells. A recombinant MVA-based vector for vaccination with different fluorescent reporter genes was developed by Antonio Siccardi, which indicate the progress of genetic recombination with the transgene of an antigen (green, colorless, red).
MVA is widely considered as the vaccinia virus strain of choice for clinical investigation because of its high safety profile. MVA has been administered to numerous animal species including monkeys, mice, swine, sheep, cattle, horses, and elephants, with no local or systemic adverse effects. Over 120,000 humans have been safely and successfully vaccinated against smallpox with MVA by intradermal, subcutaneous, or intramuscular injections.
Currently, the use of MVA as a recombinant HIV vaccine (MVA-B) is being tested in approximately 300 volunteers in several Phase I studies conducted by the International AIDS Vaccine Initiative. Studies in mice and nonhuman primates have further demonstrated the safety of MVA under conditions of immune suppression. Compared to replicating vaccinia viruses, MVA provides similar or higher levels of recombinant gene expression even in non-permissive cells.
Recently, vaccination with smallpox vaccine (a vaccinia virus related to MVA) has been shown, on rare occasions, to cause heart problems in people who received it: heart inflammation (myocarditis), inflammation of the membrane covering the heart (pericarditis), and a combination of these two problems (myopericarditis). A few cases of cardiac chest pain (angina) and heart attack have also been reported following smallpox vaccination. It is not known at this time if smallpox vaccination causes angina or heart attacks. MVA is an attenuated vaccinia virus and does not replicate in the human body as efficiently as vaccinia. However. Whether or not MVA can induce the same side effects as vaccinia is not known at this time.
In animal models, MVA vaccines have been found to be immunogenic and protective against various infectious agents including immunodeficiency viruses, influenza, parainfluenza, measles virus, flaviviruses, tuberculosis, Plasmodium parasites and smallpox as well as certain cancers.
A considerable amount of data on MVA vector vaccines has been accumulated from studies in macaques. In addition, combinations of viral vector vaccines have been employed successfully. Studies in mice show that fowlpox-based and MVA-based vaccines used in combination induce immunity and protection against challenge with Plasmodium parasites. In macaques, DNA-based HIV vaccines can be effectively boosted with recombinant MVA-based vaccines expressing HIV antigens.
Challenge Studies in Primates
Immunization regimens incorporating priming with DNA vaccine and boosting with recombinant MVA-based vaccine have been found to provide some protection in non-human primates following challenge with an immunodeficiency virus. While vaccination did not prevent infection in these studies, it did result in lower viral load setpoints, increased CD4 counts, and reduced morbidity and mortality in vaccinated animals, compared to controls.
- G. Antoine, F. Scheiflinger, F. Dorner, F. G. Falkner: The complete genomic sequence of the modified vaccinia Ankara strain: comparison with other orthopoxviruses. In: Virology. Band 244, Nummer 2, Mai 1998, ISSN 0042-6822, S. 365–396, doi:10.1006/viro.1998.9123, PMID 9601507.
- J. S. Kennedy, R. N. Greenberg: IMVAMUNE: modified vaccinia Ankara strain as an attenuated smallpox vaccine. In: Expert review of vaccines. Band 8, Nummer 1, Januar 2009, ISSN 1744-8395, S. 13–24, doi:10.1586/14760522.214.171.124, PMID 19093767.
- G. Di Lullo, E. Soprana, M. Panigada, A. Palini, Volker Erfle, C. Staib, G. Sutter, A. G. Siccardi: Marker gene swapping facilitates recombinant Modified Vaccinia Virus Ankara production by host-range selection. In: Journal of virological methods. Band 156, Nummer 1–2, März 2009, ISSN 0166-0934, S. 37–43, doi:10.1016/j.jviromet.2008.10.026, PMID 19038289.
- E. Soprana, M. Panigada, M. Knauf, A. Radaelli, L. Vigevani, A. Palini, C. Villa, M. Malnati, G. Cassina, Reinhard Kurth, S. Norley, A. G. Siccardi: Joint production of prime/boost pairs of Fowlpox Virus and Modified Vaccinia Ankara recombinants carrying the same transgene. In: Journal of virological methods. Band 174, Nummer 1–2, Juni 2011, ISSN 1879-0984, S. 22–28, doi:10.1016/j.jviromet.2011.03.013, PMID 21419167.
- P. Andersen, J. S. Woodworth: Tuberculosis vaccines–rethinking the current paradigm. In: Trends in immunology. Band 35, Nummer 8, August 2014, ISSN 1471-4981, S. 387–395, doi:10.1016/j.it.2014.04.006, PMID 24875637.
- R. J. Amato, M. Stepankiw: Evaluation of MVA-5T4 as a novel immunotherapeutic vaccine in colorectal, renal and prostate cancer. In: Future oncology (London, England). Band 8, Nummer 3, März 2012, ISSN 1744-8301, S. 231–237, doi:10.2217/fon.12.7, PMID 22409460.