Modified vaccinia Ankara explained

Type:vaccine
Target:Smallpox, mpox
Vaccine Type:attenuated
Tradename:Imvanex, Imvamune, Jynneos
Routes Of Administration:Subcutaneous, Intradermal
Atc Prefix:J07
Atc Suffix:BX
Legal Ca:Rx-only
Legal Ca Comment:/ Schedule D[1]
Legal Uk:POM
Legal Us:Rx-only
Legal Us Comment:[2]
Legal Eu:Rx-only
Legal Eu Comment:[3]
Chemspiderid:none
Synonyms:MVA

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, Imvamune in Canada, and Jynneos in the US) against smallpox and mpox,[4] having fewer side effects than smallpox vaccines derived from other poxviruses.

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."

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.

Development as a poxvirus vaccine

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.

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.

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.[6] The vaccine is given subcutaneously in two doses, at least 28 days apart. It was approved in Canada in 2013, as a smallpox vaccine[7] and in 2020 also against mpox and related orthopoxvirus infections. It was approved in the European Union in 2013, as a vaccine against smallpox[8] and in the US in September 2019, against smallpox and mpox.[9] [10] [11]

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.[12]

Development as a viral vector

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.[13] 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).[14] [15]

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

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. After removing a certain MVA gene, the vaccine produced an improved immune response in mice.[18]

Research

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.[19]

Further reading

Notes and References

  1. Web site: Product Monograph including Patient Medication Information - Imvamune. 26 November 2021. 19 June 2022. 26 May 2022. https://web.archive.org/web/20220526154523/https://pdf.hres.ca/dpd_pm/00063755.PDF. live.
  2. Web site: Jynneos- vaccinia virus modified strain ankara-bavarian nordic non-replicating antigen injection, suspension . DailyMed . 14 February 2022 . 26 May 2022 . 27 May 2022 . https://web.archive.org/web/20220527035655/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=69fc3841-a461-4706-bdcb-1176c40bf486 . live .
  3. Web site: Imvanex EPAR . 2 October 2014 . European Medicines Agency (EMA) . 27 April 2022 . https://web.archive.org/web/20220427235228/https://www.ema.europa.eu/en/medicines/human/EPAR/imvanex . live .
  4. Web site: June 2022. NACI Rapid Response - Interim guidance on the use of Imvamune in the context of monkeypox outbreaks in Canada. Public Health Agency of Canada. 19 June 2022. 19 June 2022. https://web.archive.org/web/20220619052249/https://www.canada.ca/content/dam/phac-aspc/documents/services/immunization/national-advisory-committee-on-immunization-naci/guidance-imvamune-monkeypox/guidance-imvamune-monkeypox-en.pdf. live.
  5. Volz A, Sutter G . Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development . Advances in Virus Research . 97 . 187–243 . 2017 . 28057259 . 7112317 . 10.1016/bs.aivir.2016.07.001 .
  6. Kennedy JS, Greenberg RN . IMVAMUNE: modified vaccinia Ankara strain as an attenuated smallpox vaccine . Expert Review of Vaccines . 8 . 1 . 13–24 . January 2009 . 19093767 . 9709931 . 10.1586/14760584.8.1.13 . 35854977 .
  7. Web site: Products for Human Use. Submission #144762. 13 June 2014. Health Canada. 144762 (Submission Number). https://web.archive.org/web/20140617224429/http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/regist/reg_innov_dr-eng.php. 17 June 2014. Register of Innovative Drugs. 26 June 2014.
  8. Web site: Imvanex. 27 May 2016. European Medicines Agency. Human Medicines. 12 June 2016. 20 June 2018. https://web.archive.org/web/20180620154521/http://www.ema.europa.eu/ema//index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F002596%2Fhuman_med_001666.jsp&mid=WC0b01ac058001d124#authorisation. live.
  9. Web site: FDA approves first live, non-replicating vaccine to prevent smallpox and monkeypox . U.S. Food and Drug Administration (FDA) . 24 September 2019 . https://web.archive.org/web/20191017055501/https://www.fda.gov/news-events/press-announcements/fda-approves-first-live-non-replicating-vaccine-prevent-smallpox-and-monkeypox . 17 October 2019 . live . 17 October 2019.
  10. Web site: Smallpox Vaccine Supply & Strength . National Institute of Allergy and Infectious Diseases (NIAID) . 26 September 2019 . https://web.archive.org/web/20191017060706/https://www.niaid.nih.gov/diseases-conditions/smallpox-vaccine . 17 October 2019 . live . 16 October 2019.
  11. Greenberg RN, Hay CM, Stapleton JT, Marbury TC, Wagner E, Kreitmeir E, Röesch S, von Krempelhuber A, Young P, Nichols R, Meyer TP, Schmidt D, Weigl J, Virgin G, Arndtz-Wiedemann N, Chaplin P . 6 . 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 . 2016 . 27327616 . 4915701 . 10.1371/journal.pone.0157335 . doi . free . 2016PLoSO..1157335G .
  12. 9 August 2022 . Monkeypox Update: FDA Authorizes Emergency Use of Jynneos Vaccine to Increase Vaccine Supply . 14 August 2022 . U.S. Food and Drug Administration (FDA) .
  13. Book: Pavot V, Sebastian S, Turner AV, Matthews J, Gilbert SC . Recombinant Virus Vaccines . Generation and Production of Modified Vaccinia Virus Ankara (MVA) as a Vaccine Vector . Methods in Molecular Biology . 1581 . 97–119 . 4 April 2017 . 28374245 . 10.1007/978-1-4939-6869-5_6 . Springer New York . 9781493968671 .
  14. . 6 . Marker gene swapping facilitates recombinant Modified Vaccinia Virus Ankara production by host-range selection . Journal of Virological Methods . 156 . 1–2 . 37–43 . March 2009 . 19038289 . 10.1016/j.jviromet.2008.10.026 .
  15. Soprana E, Panigada M, Knauf M, Radaelli A, Vigevani L, Palini A, Villa C, Malnati M, Cassina G, Kurth R, Norley S, Siccardi AG . 6 . 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 . June 2011 . 21419167 . 10.1016/j.jviromet.2011.03.013 . 6 July 2022 . live . https://web.archive.org/web/20220706064109/https://edoc.rki.de/handle/176904/1157 . 6 July 2022 .
  16. Andersen P, Woodworth JS . Tuberculosis vaccines--rethinking the current paradigm . Trends in Immunology . 35 . 8 . 387–395 . August 2014 . 24875637 . 10.1016/j.it.2014.04.006 .
  17. Amato RJ, Stepankiw M . Evaluation of MVA-5T4 as a novel immunotherapeutic vaccine in colorectal, renal and prostate cancer . Future Oncology . 8 . 3 . 231–237 . March 2012 . 22409460 . 10.2217/fon.12.7 .
  18. Pérez P, Marín MQ, Lázaro-Frías A, Sorzano CÓ, Gómez CE, Esteban M, García-Arriaza J . Deletion of Vaccinia Virus A40R Gene Improves the Immunogenicity of the HIV-1 Vaccine Candidate MVA-B . Vaccines . 8 . 1 . 70 . February 2020 . 32041218 . 7158668 . 10.3390/vaccines8010070 . doi . free .
  19. Kuehn BM . Single Monkeypox Vaccine Dose Provides Some Protection . JAMA . 328 . 18 . 1801 . November 2022 . 36346407 . 10.1001/jama.2022.18452 . 253396637 . free .

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