Modified vaccinia Ankara

Modified vaccinia AnkaraVaccine description

Target disease| Smallpox, mpox
Type| Attenuated virus
Names
Trade names| Imvanex, Imvamune, Jynneos
Other names| MVA
Clinical data
Routes of
use| Subcutaneous, Intradermal[1]
External links
AHFS/Drugs.com| Professional Drug Facts
Legal
Legal status|

* CA: ℞-only / Schedule D[2]
* UK: POM (Prescription only)
* US: ℞-only [1]
* EU: Rx-only [3]

Identifiers
ChemSpider|

* none

ATC code|

* J07BX (WHO)

Modified vaccinia Ankara (MVA) is an attenuated (weakened) strain of the vaccinia virus. It is being used as a vaccine (called MVA-BN, brand names: Imvanex in the EU,[3] Imvamune in Canada,[2] and Jynneos in the US[1]) against smallpox and mpox,[4] having fewer side effects than smallpox vaccines derived from other poxviruses.[5]

This third-generation smallpox vaccine has the advantage that it cannot reproduce complete virions in human cells, "the block of the MVA life cycle occurs at the step of virion assembly resulting in assembly of immature virus particles that are not released from the infected cell."[5]

By inserting antigen genes into its genome, modified vaccinia Ankara virus is also used as an experimental viral vector for vaccines against non-poxvirus diseases.[6]

## Contents

* 1 Development as a poxvirus vaccine
* 2 Development as a viral vector
* 3 Research
* 4 References
* 5 Further reading

## Development as a poxvirus vaccine[edit | edit source]

The traditional smallpox vaccine, which was used in the smallpox eradication campaign 1958–1977, consists of a live vaccinia virus which can replicate in humans but usually does not cause disease. It can however sometimes lead to serious side effects. Modified vaccinia Ankara virus is a highly attenuated strain of vaccinia virus that was developed in Munich, Germany between 1953 and 1968. It was produced by more than 500 serial passages of vaccinia virus (from a wild strain discovered by the Turkish vaccine institute of Ankara) in chicken embryo fibroblasts.[5] After testing the safety and effectiveness as a vaccine, it was approved in Germany in 1977, and then given to about 120,000 people until 1980, when smallpox vaccinations ended in Germany. No severe adverse events were seen during this time.[5]

It was later found that through the passaging, modified vaccinia virus Ankara had lost about 10% of the ancestral vaccinia genome and with it the ability to replicate efficiently in most mammalian cells. While it can enter host cells, express its genes and replicate its genome, it fails to assemble virus particles that are released from the cell.[5]

The vaccine was further developed and manufactured by the Danish company Bavarian Nordic, resulting in the vaccine MVA-BN, which is unable to replicate in human cells.[7] The vaccine is given subcutaneously in two doses, at least 28 days apart.[8] It was approved in Canada in 2013, as a smallpox vaccine[9] and in 2020 also against mpox and related orthopoxvirus infections. It was approved in the European Union in 2013, as a vaccine against smallpox[3][8] and in the US in September 2019, against smallpox and mpox.[10][11][12]

In August 2022, the US Food and Drug Administration (FDA) gave emergency use authorization for intradermal (rather than subcutaneous) mpox vaccination using a lower dose of Jynneos, which would increase the number of available doses up to five-fold. The vaccination would still be given in two doses, 28 days apart. A 2015 study had tested a regimen of one-fifth dose given intradermally.[13]

## Development as a viral vector[edit | edit source]

Timeline for construction of MVA-based vaccine after a human case of infection with influenza[14]

Modified vaccinia Ankara strains engineered to express foreign genes are vectors for production of recombinant proteins, the most common being a vaccine delivery system for antigens.[6] A recombinant MVA-based vector for vaccination with different fluorescent reporter genes was developed, which indicate the progress of genetic recombination with the transgene of an antigen (green, colorless, red).[15][16]

In animal models, MVA-based vector vaccines have been found to be immunogenic and protective against various infectious agents including immunodeficiency viruses, influenza,[16] parainfluenza, measles virus, flaviviruses, tuberculosis,[17] Plasmodium parasites as well as certain cancers.[18]

MVA-B is an experimental vaccine to protect against HIV infection, produced by inserting HIV genes into the genome of modified vaccinia virus Ankara. In phase I clinical trials in 2013, it was found to be safe but produced only moderate levels of anti-HIV immunity.[19] After removing a certain MVA gene, the vaccine produced an improved immune response in mice.[20]

## Research[edit | edit source]

A US Centers for Disease Control and Prevention (CDC) analysis of the vaccination status of 5402 individuals who had mpox infections during the summer of 2022 showed that unvaccinated people appeared to be 14 times more likely to be infected than those with a single (of two recommended) doses; the results were noted to be admittedly preliminary.[21]

## References[edit | edit source]

1. ↑ 1.0 1.1 1.2 "Jynneos- vaccinia virus modified strain ankara-bavarian nordic non-replicating antigen injection, suspension". DailyMed. 14 February 2022. Archived from the original on 27 May 2022. Retrieved 26 May 2022.
2. ↑ 2.0 2.1 "Product Monograph including Patient Medication Information - Imvamune" (PDF). 26 November 2021. Archived (PDF) from the original on 26 May 2022. Retrieved 19 June 2022.
3. ↑ 3.0 3.1 3.2 "Imvanex EPAR". European Medicines Agency (EMA). Archived from the original on 27 April 2022. Retrieved 2 October 2014.
4. ↑ "NACI Rapid Response - Interim guidance on the use of Imvamune in the context of monkeypox outbreaks in Canada" (PDF). Public Health Agency of Canada. June 2022. Archived (PDF) from the original on 19 June 2022. Retrieved 19 June 2022.
5. ↑ 5.0 5.1 5.2 5.3 5.4 Volz A, Sutter G (2017). "Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development". Advances in Virus Research. 97: 187–243. doi:10.1016/bs.aivir.2016.07.001. PMC 7112317. PMID 28057259.
6. ↑ 6.0 6.1 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. Vol. 1581\. Springer New York. pp. 97–119. doi:10.1007/978-1-4939-6869-5_6. ISBN 9781493968671. PMID 28374245.
7. ↑ 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.
8. ↑ 8.0 8.1 "Imvanex". Human Medicines. European Medicines Agency. 27 May 2016. Archived from the original on 20 June 2018. Retrieved 12 June 2016.
9. ↑ "Products for Human Use. Submission #144762". Register of Innovative Drugs. Health Canada. 13 June 2014. 144762 (Submission Number). Archived from the original on 17 June 2014. Retrieved 26 June 2014.
10. ↑ "FDA approves first live, non-replicating vaccine to prevent smallpox and monkeypox". U.S. Food and Drug Administration (FDA). 24 September 2019. Archived from the original on 17 October 2019. Retrieved 17 October 2019. This article incorporates text from this source, which is in the public domain.
11. ↑ "Smallpox Vaccine Supply & Strength". National Institute of Allergy and Infectious Diseases (NIAID). 26 September 2019. Archived from the original on 17 October 2019. Retrieved 16 October 2019.
12. ↑ Greenberg RN, Hay CM, Stapleton JT, Marbury TC, Wagner E, Kreitmeir E, et al. (2016). "A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN®) in 56-80-Year-Old Subjects". PLOS ONE. 11 (6): e0157335. Bibcode:2016PLoSO..1157335G. doi:10.1371/journal.pone.0157335. PMC 4915701. PMID 27327616.
13. ↑ "Monkeypox Update: FDA Authorizes Emergency Use of Jynneos Vaccine to Increase Vaccine Supply" (Press release). U.S. Food and Drug Administration (FDA). 9 August 2022. Archived from the original on 11 August 2022. Retrieved 14 August 2022.
14. ↑ Altenburg, Arwen F.; Kreijtz, Joost H. C. M.; De Vries, Rory D.; Song, Fei; Fux, Robert; Rimmelzwaan, Guus F.; Sutter, Gerd; Volz, Asisa (July 2014). "Modified Vaccinia Virus Ankara (MVA) as Production Platform for Vaccines against Influenza and Other Viral Respiratory Diseases". Viruses. 6 (7): 2735–2761. doi:10.3390/v6072735. ISSN 1999-4915.
15. ↑ 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.
16. ↑ 16.0 16.1 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): 22–28. doi:10.1016/j.jviromet.2011.03.013. PMID 21419167. Archived from the original on 6 July 2022. Retrieved 6 July 2022.
17. ↑ Andersen P, Woodworth JS (August 2014). "Tuberculosis vaccines--rethinking the current paradigm". Trends in Immunology. 35 (8): 387–395. doi:10.1016/j.it.2014.04.006. PMID 24875637.
18. ↑ 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): 231–237. doi:10.2217/fon.12.7. PMID 22409460.
19. ↑ Clinical trial number NCT00679497 for "A Phase I Study of Modified Vaccinia Virus Ankara (MVA-B) in Healthy Volunteers at Low Risk of HIV Infection" at ClinicalTrials.gov
20. ↑ Pérez P, Marín MQ, Lázaro-Frías A, Sorzano CÓ, Gómez CE, Esteban M, García-Arriaza J (February 2020). "Deletion of Vaccinia Virus A40R Gene Improves the Immunogenicity of the HIV-1 Vaccine Candidate MVA-B". Vaccines. 8 (1): 70. doi:10.3390/vaccines8010070. PMC 7158668. PMID 32041218.
21. ↑ Kuehn BM (November 2022). "Single Monkeypox Vaccine Dose Provides Some Protection". JAMA. 328 (18): 1801. doi:10.1001/jama.2022.18452. PMID 36346407. S2CID 253396637.

## Further reading[edit | edit source]

* Altenburg AF, Kreijtz JH, de Vries RD, Song F, Fux R, Rimmelzwaan GF, et al. (July 2014). "Modified vaccinia virus ankara (MVA) as production platform for vaccines against influenza and other viral respiratory diseases". Viruses. 6 (7): 2735–2761. doi:10.3390/v6072735. PMC 4113791. PMID 25036462.

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