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 monkeypox, having fewer side effects than the traditional smallpox vaccine. 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 Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism (''in vivo'') or in cell culture (''in vitro''). Viruses have evolved specialized molecul ...

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 Ankara ( , ; ), historically known as Ancyra and Angora, is the capital of Turkey. Located in the central part of Anatolia, the city has a population of 5.1 million in its urban center and over 5.7 million in Ankara Province, mak ...

) in chicken embryo fibroblasts. 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. The vaccine is given subcutaneously in two doses, at least 28 days apart. It was approved in Canada in 2013, as a smallpox vaccine and in 2020 also against monkeypox and related orthopoxvirus infections. It was approved in the European Union in 2013, as a vaccine against smallpox and in the US in September 2019, against smallpox and monkeypox. In August 2022, the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) gave emergency use authorization for intradermal (rather than subcutaneous) monkeypox 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.

Development as a viral vector

Modified vaccinia Ankara strains engineered to express foreign

genes In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

are vectors for production of recombinant proteins, the most common being a vaccine delivery system for antigens. A recombinant MVA-based vector for vaccination with different fluorescent reporter genes was developed, which indicate the progress of

genetic recombination Genetic recombination (also known as genetic reshuffling) is the exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent. In eukaryo ...

with the transgene of an

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

(green, colorless, red). In animal models, MVA-based vector vaccines have been found to be immunogenic and protective against various infectious agents including immunodeficiency viruses,

influenza Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms ...

, parainfluenza,

measles Measles is a highly contagious infectious disease caused by Measles morbillivirus, measles virus. Symptoms usually develop 10–12 days after exposure to an infected person and last 7–10 days. Initial symptoms typically include fever, often ...

virus, flaviviruses,

tuberculosis Tuberculosis (TB) is an infectious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in w ...

, '' Plasmodium'' parasites as well as certain

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...

s. 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.

Research

A US Centers for Disease Control and Prevention (CDC) analysis of the vaccination status of 5402 individuals who had monkeypox 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.

Development as a poxvirus vaccine

Development as a viral vector

Research

References

Further reading