Modified vaccinia Ankara
Encyclopedia
Vaccinia
virus
es re-engineered to express foreign genes
are robust vectors for production of recombinant proteins, the most common being a vaccine
delivery system for antigens. Concerns about the safety of the vaccinia virus have been addressed by the development of vectors based on attenuated vaccinia viruses. One of them, the Modified Vaccinia Ankara (MVA) virus, is a highly attenuated strain of vaccinia virus that was developed towards the end of the campaign for the eradication of smallpox
by Professor Anton Mayr in Germany. Produced by hundreds of passages of vaccinia virus in chicken
cells
, MVA has lost about 10% of the vaccinia genome and with it the ability to replicate efficiently in primate
cells.
, swine, sheep, cattle
, horses, and elephants, with no local or systemic adverse
effects. Over 120,000 humans have been safely and successfully vaccinated against smallpox
with MVA by intradermal, subcutaneous, or intramuscular injections. Currently, the use of MVA as a recombinant HIV
vaccine (MVA-B
) is being tested in approximately 300 volunteers in several Phase I studies conducted by the International AIDS Vaccine Initiative
. Studies in mice and nonhuman primates have further demonstrated the safety of MVA under conditions of immune
suppression.
Recently, vaccination with smallpox vaccine (a vaccinia virus related to MVA) has been shown, on rare occasions, to cause heart problems in people who received it: heart inflammation (myocarditis
), inflammation of the membrane covering the heart (pericarditis
), and a combination of these two problems (myopericarditis
). A few cases of cardiac chest pain (angina
) and heart attack have also been reported following smallpox vaccination. It is not known at this time if smallpox vaccination causes angina or heart attacks. MVA is an attenuated vaccinia virus and does not replicate in the human body as efficiently as vaccinia. However, whether MVA can induce the same side effects as vaccinia is not known at this time.
Compared to replicating vaccinia viruses, MVA provides similar or higher levels of recombinant gene expression even in non-permissive
cells. In animal models, recombinant MVA vaccines have been found immunogenic and to protect against various infectious agents including influenza, parainfluenza, measles virus, flaviviruses, and plasmodium parasites.
, parainfluenza, measles
virus, flaviviruses, tuberculosis
, Plasmodium
parasites and smallpox.
A considerable amount of data on MVA vector vaccines has been accumulated from studies in macaques.
In addition, combinations of viral vector vaccines have been employed successfully. Studies in mice show that fowlpox
-based and MVA-based vaccines used in combination induce immunity and protection against challenge with Plasmodium parasites. In macaques, DNA-based HIV vaccines can be effectively boosted with recombinant MVA-based vaccines expressing HIV antigens.
Vaccinia
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, and which encodes for approximately 250 genes. The dimensions of the virion are roughly 360 × 270 × 250 nm, with a mass of...
virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es re-engineered to express foreign genes
Gênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
are robust vectors for production of recombinant proteins, the most common being a vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
delivery system for antigens. Concerns about the safety of the vaccinia virus have been addressed by the development of vectors based on attenuated vaccinia viruses. One of them, the Modified Vaccinia Ankara (MVA) virus, is a highly attenuated strain of vaccinia virus that was developed towards the end of the campaign for the eradication of smallpox
Smallpox
Smallpox was an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning "spotted", or varus, meaning "pimple"...
by Professor Anton Mayr in Germany. Produced by hundreds of passages of vaccinia virus in chicken
Chicken
The chicken is a domesticated fowl, a subspecies of the Red Junglefowl. As one of the most common and widespread domestic animals, and with a population of more than 24 billion in 2003, there are more chickens in the world than any other species of bird...
cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
, MVA has lost about 10% of the vaccinia genome and with it the ability to replicate efficiently in primate
Primate
A primate is a mammal of the order Primates , which contains prosimians and simians. Primates arose from ancestors that lived in the trees of tropical forests; many primate characteristics represent adaptations to life in this challenging three-dimensional environment...
cells.
Modified vaccinia Ankara in clinical trials
MVA is widely considered as the vaccinia virus strain of choice for clinical investigation because of its high safety profile. MVA has been administered to numerous animal species including monkeys, miceMICE
-Fiction:*Mice , alien species in The Hitchhiker's Guide to the Galaxy*The Mice -Acronyms:* "Meetings, Incentives, Conferencing, Exhibitions", facilities terminology for events...
, swine, sheep, cattle
Cattle
Cattle are the most common type of large domesticated ungulates. They are a prominent modern member of the subfamily Bovinae, are the most widespread species of the genus Bos, and are most commonly classified collectively as Bos primigenius...
, horses, and elephants, with no local or systemic adverse
Adverse
Adverse or adverse interest, in law, is anything that functions contrary to a party's interest. This word should not be confused with averse.-Adverse possession:...
effects. Over 120,000 humans have been safely and successfully vaccinated against smallpox
Smallpox
Smallpox was an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning "spotted", or varus, meaning "pimple"...
with MVA by intradermal, subcutaneous, or intramuscular injections. Currently, the use of MVA as a recombinant HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
vaccine (MVA-B
MVA-B
MVA-B, or Modified Vaccinia Ankara B, is a particular HIV vaccine created to give immune resistance to infection by the HIV 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...
) is being tested in approximately 300 volunteers in several Phase I studies conducted by the International AIDS Vaccine Initiative
International AIDS Vaccine Initiative
The International AIDS Vaccine Initiative is a global not-for-profit, public-private partnership working to accelerate the development of vaccines to prevent HIV infection and AIDS. IAVI researches and develops vaccine candidates, conducts policy analyses, serves as an advocate for the field and...
. Studies in mice and nonhuman primates have further demonstrated the safety of MVA under conditions of immune
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
suppression.
Recently, vaccination with smallpox vaccine (a vaccinia virus related to MVA) has been shown, on rare occasions, to cause heart problems in people who received it: heart inflammation (myocarditis
Myocarditis
Myocarditis is inflammation of heart muscle . It resembles a heart attack but coronary arteries are not blocked.Myocarditis is most often due to infection by common viruses, such as parvovirus B19, less commonly non-viral pathogens such as Borrelia burgdorferi or Trypanosoma cruzi, or as a...
), inflammation of the membrane covering the heart (pericarditis
Pericarditis
Pericarditis is an inflammation of the pericardium . A characteristic chest pain is often present.The causes of pericarditis are varied, including viral infections of the pericardium, idiopathic causes, uremic pericarditis, bacterial infections of the precardium Pericarditis is an inflammation of...
), and a combination of these two problems (myopericarditis
Myopericarditis
Myopericarditis is a combination of both myocarditis and pericarditis appearing in a single individual. It is when fluid is in the heart. Myopericarditis refers primarily to a pericarditis with lesser myocarditis, as opposed to a perimyocarditis, though the two terms are often used interchangeably....
). A few cases of cardiac chest pain (angina
Angina
Angina pectoris, commonly known as angina, is chest pain due to ischemia of the heart muscle, generally due to obstruction or spasm of the coronary arteries . Coronary artery disease, the main cause of angina, is due to atherosclerosis of the cardiac arteries...
) and heart attack have also been reported following smallpox vaccination. It is not known at this time if smallpox vaccination causes angina or heart attacks. MVA is an attenuated vaccinia virus and does not replicate in the human body as efficiently as vaccinia. However, whether MVA can induce the same side effects as vaccinia is not known at this time.
Compared to replicating vaccinia viruses, MVA provides similar or higher levels of recombinant gene expression even in non-permissive
Permissive
When a cell or host is defined as permissive in virology, it refers to the fact that the virus is able to circumvent host defenses and is able to replicate. Usually this occurs when the virus has modulated one or several of the host cellular intrinsic defenses, and the host immune system...
cells. In animal models, recombinant MVA vaccines have been found immunogenic and to protect against various infectious agents including influenza, parainfluenza, measles virus, flaviviruses, and plasmodium parasites.
Immunogenicity
In animal models, MVA vaccines have been found to be immunogenic and protective against various infectious agents including immunodeficiency viruses, influenzaInfluenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
, parainfluenza, measles
Measles
Measles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...
virus, flaviviruses, tuberculosis
MVA85A
MVA85A is a new-generation vaccine against tuberculosis developed by researchers at Oxford University. This vaccine produces higher levels of long-lasting cellular immunity when used together with the old TB vaccine called BCG. Phase I clinical trials have been completed and phase II clinical...
, Plasmodium
Plasmodium
Plasmodium is a genus of parasitic protists. Infection by these organisms is known as malaria. The genus Plasmodium was described in 1885 by Ettore Marchiafava and Angelo Celli. Currently over 200 species of this genus are recognized and new species continue to be described.Of the over 200 known...
parasites and smallpox.
A considerable amount of data on MVA vector vaccines has been accumulated from studies in macaques.
In addition, combinations of viral vector vaccines have been employed successfully. Studies in mice show that fowlpox
Fowlpox
Fowlpox is a worldwide disease of poultry caused by viruses of the family Poxviridae and the genus Avipoxvirus. The viruses causing fowlpox are distinct from one another but antigenically similar, possible hosts including chickens, turkeys, quail, canaries, pigeons, and many other species of...
-based and MVA-based vaccines used in combination induce immunity and protection against challenge with Plasmodium parasites. In macaques, DNA-based HIV vaccines can be effectively boosted with recombinant MVA-based vaccines expressing HIV antigens.