Modified vaccinia Ankara

Modified vaccinia Ankara
Vaccine description
Target	Smallpox, mpox
Vaccine type	Attenuated
Clinical data
Trade names	Imvanex, Imvamune, Jynneos
Other names	MVA
AHFS/Drugs.com	Professional Drug Facts
Routes of; administration	Subcutaneous, Intradermal
ATC code	J07BX ( WHO );
Legal status
Legal status	CA: ℞-only / Schedule D; UK: POM (Prescription only); US: ℞-only ; EU:Rx-only;
Identifiers
ChemSpider	none;

Last updated February 05, 2024

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]

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.^[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

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).^[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,^[15] 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.^[18] After removing a certain MVA gene, the vaccine produced an improved immune response in mice.^[19]

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.^[20]

Related Research Articles

A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.

The smallpox vaccine is the first vaccine to have been developed against a contagious disease. In 1796, British physician Edward Jenner demonstrated that an infection with the relatively mild cowpox virus conferred immunity against the deadly smallpox virus. Cowpox served as a natural vaccine until the modern smallpox vaccine emerged in the 20th century. From 1958 to 1977, the World Health Organization (WHO) conducted a global vaccination campaign that eradicated smallpox, making it the only human disease to be eradicated. Although routine smallpox vaccination is no longer performed on the general public, the vaccine is still being produced to guard against bioterrorism, biological warfare, and mpox.

<span class="mw-page-title-main">Mpox</span> Infectious viral disease

Mpox is an infectious viral disease that can occur in humans and some other animals. Symptoms include a rash that forms blisters and then crusts over, fever, and swollen lymph nodes. The illness is usually mild and most of those infected will recover within a few weeks without treatment. The time from exposure to onset of symptoms ranges from five to twenty-one days and symptoms typically last from two to four weeks. Cases may be severe, especially in children, pregnant women or people with suppressed immune systems.

Vaccinia virus is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, which encodes approximately 250 genes. The dimensions of the virion are roughly 360 × 270 × 250 nm, with a mass of approximately 5–10 fg. The vaccinia virus is the source of the modern smallpox vaccine, which the World Health Organization (WHO) used to eradicate smallpox in a global vaccination campaign in 1958–1977. Although smallpox no longer exists in the wild, vaccinia virus is still studied widely by scientists as a tool for gene therapy and genetic engineering.

Orthopoxvirus is a genus of viruses in the family Poxviridae and subfamily Chordopoxvirinae. Vertebrates, including mammals and humans, and arthropods serve as natural hosts. There are 12 species in this genus. Diseases associated with this genus include smallpox, cowpox, horsepox, camelpox, and monkeypox. The most widely known member of the genus is Variola virus, which causes smallpox. It was eradicated globally by 1977, through the use of Vaccinia virus as a vaccine. The most recently described species is the Alaskapox virus, first isolated in 2015.

TroVax is a cancer vaccine that was developed by Oxford BioMedica. No cancer vaccines have been proven to cure cancer or extend life yet, TroVax has been studied in a number of trials for colon cancer.

GeoVax is a clinical-stage biotechnology company which develops vaccines. GeoVax's development platform uses Modified Vaccinia Ankara (MVA) vector technology, with improvements to antigen design and manufacturing capabilities. GeoVax uses recombinant DNA or recombinant viruses to produce virus-like particles (VLPs) in the person being vaccinated.

MVA-B, or Modified Vaccinia Ankara B, is an HIV vaccine created to give immune resistance to infection by the human immunodeficiency virus. It was developed by a team of Spanish researchers at the Spanish National Research Council's Biotechnology National Centre headed by Dr. Mariano Esteban. The vaccine is based on the Modified vaccinia Ankara (MVA) virus used during the 1970s to help eradicate the smallpox virus. The B in the name "refers to HIV-B, the most common HIV subtype in Europe". It has been stated by Dr. Esteban that, in the future, the vaccine could potentially reduce the virulence of HIV to a "minor chronic infection akin to herpes".

The monkeypox virus, is a species of double-stranded DNA virus that causes mpox disease in humans and other mammals. The monkeypox virus is a zoonotic virus belonging to the orthopoxvirus genus, making it closely related to the variola, cowpox, and vaccinia viruses. MPV is oval-shaped with a lipoprotein outer membrane. The genome is approximately 190 kb.

Vaccinia immune globulin (VIG) is made from the pooled blood of individuals who have been inoculated with the smallpox vaccine. The antibodies these individuals developed in response to the smallpox vaccine are removed and purified. This results in VIG. It can be administered intravenously. It is used to treat individuals who have developed progressive vaccinia after smallpox vaccination.

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Ebola vaccines are vaccines either approved or in development to prevent Ebola. As of 2022, there are only vaccines against the Zaire ebolavirus. The first vaccine to be approved in the United States was rVSV-ZEBOV in December 2019. It had been used extensively in the Kivu Ebola epidemic under a compassionate use protocol. During the early 21st century, several vaccine candidates displayed efficacy to protect nonhuman primates against lethal infection.

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Raccoonpox virus (RCN) is a double-stranded DNA virus and a member of the orthopoxviruses in the family Poxviridae and subfamily Chordopoxvirinae which consists of eight genera: Avipoxvirus, Capripoxvirus, Leporipoxvirus, Molluscipoxvirus, Orthopoxvirus, Parapoxvirus, Suipoxvirus and Yatapoxvirus Vertebrates are the natural host of Chordopoxvirinae subfamily viruses. More specifically, raccoons are the natural hosts of RCN. RCN was isolated in 1961 from the upper respiratory tissues of 2 raccoons in a group of 92 observably healthy raccoons trapped close to Aberdeen, Maryland.

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A viral vector vaccine is a vaccine that uses a viral vector to deliver genetic material (DNA) that can be transcribed by the recipient's host cells as mRNA coding for a desired protein, or antigen, to elicit an immune response. As of April 2021, six viral vector vaccines, four COVID-19 vaccines and two Ebola vaccines, have been authorized for use in humans.

A genetic vaccine is a vaccine that contains nucleic acids such as DNA or RNA that lead to protein biosynthesis of antigens within a cell. Genetic vaccines thus include DNA vaccines, RNA vaccines and viral vector vaccines.

The 2022–2023 mpox outbreak in the United States is part of the larger outbreak of human mpox caused by the West African clade of the monkeypox virus. The United States was the fourth country outside of the African countries with endemic mpox, to experience an outbreak in 2022. The first case was documented in Boston, Massachusetts, on May 17, 2022. As of August 22, mpox has spread to all 50 states in the United States, as well as Washington, D.C., and Puerto Rico. The United States has the highest number of mpox cases in the world. California has the highest number of mpox cases in the United States.

Polyvalent influenza vaccine is a type of influenza vaccine that provides immunity against more than one type of antigen. In the second week after receiving the flu shot, the body's immune system is triggered by the antigens so the body starts producing antibodies. These antibodies help fight against influenza viruses. Influenza symptoms and deaths can be prevented by getting an influenza vaccine every year. Currently circulating influenza strains that can cause seasonal epidemics include influenza A viruses, which can be further divided into subtype A(H1N1) and A(H3N2), and influenza B viruses.

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References

1 2 3 "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.
1 2 "Product Monograph including Patient Medication Information - Imvamune" (PDF). 26 November 2021. Archived (PDF) from the original on 26 May 2022. Retrieved 19 June 2022.
1 2 3 "Imvanex EPAR". European Medicines Agency (EMA). Archived from the original on 27 April 2022. Retrieved 2 October 2014.
↑ "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.
1 2 3 4 5 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.
1 2 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.
↑ 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. PMC 9709931 . PMID 19093767. S2CID 35854977.
1 2 "Imvanex". Human Medicines. European Medicines Agency. 27 May 2016. Archived from the original on 20 June 2018. Retrieved 12 June 2016.
↑ "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.
↑ "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 .
↑ "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.
↑ 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.
↑ "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. Retrieved 14 August 2022.
↑ 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.
1 2 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.
↑ 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.
↑ 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.
↑ 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
↑ 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.
↑ 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.