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 September 14, 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] On 13 September 2024, the WHO has granted prequalification status to the MVA-BN vaccine, as the first vaccine approved for use against mpox.^[13]

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.^[14]

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).^[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

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]

Related Research Articles

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 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 for research, and to guard against bioterrorism, biological warfare, and mpox.

<span class="mw-page-title-main">Mpox</span> Viral disease of humans and animals

Mpox 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, and most infected individuals recover within a few weeks without treatment. The time from exposure to the onset of symptoms ranges from three to seventeen days, and symptoms typically last from two to four weeks. However, cases may be severe, especially in children, pregnant women, or people with suppressed immune systems.

The 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 mpox. 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.

Viral vectors are modified viruses designed to deliver genetic material into cells. This process can be performed inside an organism or in cell culture. Viral vectors have widespread applications in basic research, agriculture, and medicine.

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.

ACAM2000 is a smallpox vaccine and an mpox vaccine manufactured by Emergent Biosolutions. It provides protection against smallpox for people determined to be at high risk for smallpox infection. ACAM2000 is a live replicating vaccinia virus vaccine.

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. It is a zoonotic virus belonging to the Orthopoxvirus genus, making it closely related to the variola, cowpox, and vaccinia viruses. MPV is oval, with a lipoprotein outer membrane. The genome is approximately 190 kb. Smallpox and monkeypox viruses are both orthopoxviruses, and the smallpox vaccine is effective against mpox if given within 3–5 years before the disease is contracted. Symptoms of mpox in humans include a rash that forms blisters and then crusts over, fever, and swollen lymph nodes. The virus is transmissible between animals and humans by direct contact to the lesions or bodily fluids. The virus was given the name monkeypox virus after being isolated from monkeys, but most of the carriers of this virus are smaller mammals.

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.

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 and Thörishaus near Bern, Switzerland. The company has research and development facilities in Martinsried, Germany and San Diego, California, as well as offices in Zug, Switzerland, and Morrisville, North Carolina. The company uses viral vectors and virus-like particles in its research and development.

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.

Antonio G. Siccardi is an Italian immunologist and virologist.

Raccoonpox virus (RCN) is a double-stranded DNA virus and a member of the orthopoxviruses in the family Poxviridae and subfamily Chordopoxvirinae. 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.

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 was 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 2022, mpox had spread to all 50 states in the United States, as well as Washington, D.C., and Puerto Rico. The United States had the highest number of mpox cases in the world during the outbreak. California had the highest number of mpox cases in the United States.

The 2022–2023 mpox outbreak in Germany is part of an ongoing global outbreak of human mpox caused by the West African clade of the monkeypox virus. At the beginning of September 2022, Spain, France, Germany and the United Kingdom are the countries with most cumulative cases in Europe.

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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