Modified vaccinia Ankara (MVA) is an attenuated (weakened) strain of the

vaccinia The vaccinia virus (VACV or VV) 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 ...

virus. It is being used as a

vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...

(called MVA-BN, brand names: Imvanex in the EU, Imvamune in Canada, and Jynneos in the US) against

smallpox Smallpox was an infectious disease caused by Variola virus (often called Smallpox virus), which belongs to the genus '' Orthopoxvirus''. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (W ...

and

mpox Mpox (, ; formerly known as monkeypox) is an infectious viral disease that can occur in humans and other animals. Symptoms include a rash that forms blisters and then crusts over, fever, and swollen lymph nodes. The illness is usually mild, ...

, having fewer side effects than

smallpox vaccine The smallpox vaccine is used to prevent smallpox infection caused by the variola virus. It is the first vaccine to have been developed against a contagious disease. In 1796, British physician Edward Jenner demonstrated that an infection with th ...

s derived from other

poxviruses ''Poxviridae'' is a family of double-stranded DNA viruses. Vertebrates and arthropods serve as natural hosts. The family contains 22 genera that are assigned to two subfamilies: ''Chordopoxvirinae'' and ''Entomopoxvirinae''. ''Entomopoxvirinae'' ...

. 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 A viral vector is a modified virus designed to gene delivery, deliver genetic material into cell (biology), cells. This process can be performed inside an organism or in cell culture. Viral vectors have widespread applications in basic research, ...

for vaccines against non-

poxvirus ''Poxviridae'' is a family of double-stranded DNA viruses. Vertebrates and arthropods serve as natural hosts. The family contains 22 genera that are assigned to two subfamilies: ''Chordopoxvirinae'' and ''Entomopoxvirinae''. ''Entomopoxvirinae'' ...

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 is the capital city of Turkey and List of national capitals by area, the largest capital by area in the world. Located in the Central Anatolia Region, central part of Anatolia, the city has a population of 5,290,822 in its urban center ( ...

) in chicken embryo

fibroblast A fibroblast is a type of cell (biology), biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and ...

s. 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 Express, The Expresss or EXPRESS may refer to: Arts, entertainment and media Film * ''Express: Aisle to Glory'', a 1998 comedy short film featuring Kal Penn * ''The Express: The Ernie Davis Story'', a 2008 film starring Dennis Quaid * The Expre ...

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 Bavarian Nordic A/S is a fully integrated biotechnology company focused on the development, manufacturing and commercialization of vaccines. The company is headquartered in Hellerup, Denmark, with manufacturing facilities in Kvistgård, Denmark ...

, resulting in the vaccine MVA-BN, which is unable to replicate in human cells. The vaccine is given

subcutaneously The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, or superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and m ...

in two doses, at least 28 days apart. It was approved in Canada in 2013, as a smallpox vaccine and in 2020 also against mpox and related

orthopoxvirus ''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 wi ...

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 mpox. On 13 September 2024, the WHO has granted prequalification status to the MVA-BN vaccine, as the first vaccine approved for use against mpox. In August 2022, the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) gave emergency use authorization for

intradermal Intradermal injection (also intracutaneous or intradermic, abbreviated as ID) is a shallow or superficial injection of a substance into the dermis, which is located between the epidermis and the hypodermis. For certain substances, administration ...

(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.

Development as a viral vector

Modified vaccinia Ankara strains engineered to express foreign

genes In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

are vectors for production of recombinant proteins, the most common being a

delivery system for

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

. A recombinant MVA-based vector for vaccination with different fluorescent

reporter gene Reporter genes are molecular tools widely used in molecular biology, genetics, and biotechnology to study gene function, expression patterns, and regulatory mechanisms. These genes encode proteins that produce easily detectable signals, such as ...

s 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 eukaryot ...

with the

transgene A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...

of an

antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, 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 sympto ...

parainfluenza Human parainfluenza viruses (HPIVs) are the viruses that cause human parainfluenza. HPIVs are a paraphyletic group of four distinct single-stranded RNA viruses belonging to the ''Paramyxoviridae'' family. These viruses are closely associated with ...

measles Measles (probably from Middle Dutch or Middle High German ''masel(e)'', meaning "blemish, blood blister") is a highly contagious, Vaccine-preventable diseases, vaccine-preventable infectious disease caused by Measles morbillivirus, measles v ...

virus,

flaviviruses ''Flavivirus'', renamed ''Orthoflavivirus'' in 2023, is a genus of positive-strand RNA viruses in the family ''Flaviviridae''. The genus includes the West Nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus, Zika viru ...

tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...

, ''

Plasmodium ''Plasmodium'' is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of ''Plasmodium'' species involve development in a Hematophagy, blood-feeding insect host (biology), host which then inj ...

'' parasites as well as certain

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

s. MVA-B is an experimental vaccine to protect against

HIV infection The human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a preventable disease. It can ...

, 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 The Centers for Disease Control and Prevention (CDC) is the National public health institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency under the United S ...

(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.

Development as a poxvirus vaccine

Development as a viral vector

Research

References

Further reading