Modified vaccinia Ankara

The Modified Vaccinia Ankara (MVA) is an attenuated vaccine of a poxvirus.[1][2] It was licensed and used as a poxvirus vaccine in Bavaria and is a vector for vaccination against non-poxvirus diseases.

Properties

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.[3] 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 Munich, Germany. Produced between 1953 and 1968 by more than 500 serial passages of vaccinia virus (from a wild strain discovered by the Turkish vaccine institute of Ankara) in chicken cells[4] (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).[5][6]

Clinical trials

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.

Immunogenicity

In animal models, MVA vaccines have been found to be immunogenic and protective against various infectious agents including immunodeficiency viruses, influenza,[6] parainfluenza, measles virus, flaviviruses, tuberculosis,[7] Plasmodium parasites and smallpox as well as certain cancers.[8]

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.

References
  1. Antoine G, Scheiflinger F, Dorner F, Falkner FG (May 1998). "The complete genomic sequence of the modified vaccinia Ankara strain: comparison with other orthopoxviruses". Virology. 244 (2): 365–96. doi:10.1006/viro.1998.9123. PMID 9601507.
  2. Kennedy JS, Greenberg RN (January 2009). "IMVAMUNE: modified vaccinia Ankara strain as an attenuated smallpox vaccine". Expert Review of Vaccines. 8 (1): 13–24. doi:10.1586/14760584.8.1.13. PMID 19093767. S2CID 35854977.
  3. Pavot V, Sebastian S, Turner AV, Matthews J, Gilbert SC (4 April 2017). "Generation and Production of Modified Vaccinia Virus Ankara (MVA) as a Vaccine Vector". Recombinant Virus Vaccines. Methods in Molecular Biology. 1581. Springer New York. pp. 97–119. doi:10.1007/978-1-4939-6869-5_6. ISBN 9781493968671. PMID 28374245.
  4. Volz A, Sutter G (2017). "Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development". Advances in Virus Research. Elsevier Inc. 97 (97): 187–243. doi:10.1016/bs.aivir.2016.07.001. PMC 7112317. PMID 28057259.
  5. Di Lullo G, Soprana E, Panigada M, Palini A, Erfle V, Staib C, et al. (March 2009). "Marker gene swapping facilitates recombinant Modified Vaccinia Virus Ankara production by host-range selection". Journal of Virological Methods. 156 (1–2): 37–43. doi:10.1016/j.jviromet.2008.10.026. PMID 19038289.
  6. Soprana E, Panigada M, Knauf M, Radaelli A, Vigevani L, Palini A, et al. (June 2011). "Joint production of prime/boost pairs of Fowlpox Virus and Modified Vaccinia Ankara recombinants carrying the same transgene". Journal of Virological Methods. 174 (1–2): 22–8. doi:10.1016/j.jviromet.2011.03.013. PMID 21419167.
  7. Andersen P, Woodworth JS (August 2014). "Tuberculosis vaccines--rethinking the current paradigm". Trends in Immunology. 35 (8): 387–95. doi:10.1016/j.it.2014.04.006. PMID 24875637.
  8. Amato RJ, Stepankiw M (March 2012). "Evaluation of MVA-5T4 as a novel immunotherapeutic vaccine in colorectal, renal and prostate cancer". Future Oncology. 8 (3): 231–7. doi:10.2217/fon.12.7. PMID 22409460.
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