Modified Vaccinia Ankara (MVA) is a highly attenuated, or weakened, strain of the vaccinia virus. The vaccinia virus belongs to the poxvirus family, which includes the variola virus that causes smallpox. The primary characteristic of MVA is its inability to replicate efficiently within human cells.
While it can enter cells, it cannot produce new, infectious virus particles, ensuring it cannot spread throughout the body or cause illness. This distinguishes it from older smallpox vaccines that could replicate and sometimes lead to adverse side effects.
Origin and Development of MVA
MVA was developed during the global effort to eradicate smallpox, which used vaccines with a live, replicating vaccinia virus. While effective, these first-generation vaccines carried risks of side effects, especially for individuals with weakened immune systems. This prompted a search for a safer alternative, leading to the development of MVA in Germany during the 1950s and 1960s. The original virus strain was sourced from Ankara, Turkey, which is reflected in its name.
The creation of MVA involved a technique called serial passaging. Scientists repeatedly cultivated the Ankara strain of vaccinia virus in chicken embryo fibroblast cells for over 570 cycles. This continuous adaptation to avian cells caused the virus to lose significant portions of its genetic material, amounting to over 14% of its genome.
These genetic deletions removed many genes that orthopoxviruses use to overcome the defenses of mammalian host cells. The result was a virus that could no longer complete its life cycle in humans but retained the features needed to provoke an immune response. This established MVA as a safer “third-generation” vaccine, which was administered to thousands in Germany before smallpox vaccination campaigns concluded.
How MVA Stimulates the Immune System
When administered via subcutaneous injection, MVA particles enter human cells. Because of the genetic deletions from its development, its life cycle is halted before it can assemble new virions. This prevents infectious particles from forming or being released from the infected cell.
Despite being unable to replicate, the infected human cell’s machinery reads the virus’s genetic code and produces viral proteins known as antigens. These antigens are presented on the cell’s surface, acting as signals to the immune system. This process mimics the early stages of a natural viral infection without the danger of a spreading pathogen.
The presence of these foreign proteins alerts immune cells. Antigen-presenting cells activate T-cells to identify and destroy infected cells, while B-cells are stimulated to produce antibodies. These antibodies are tailored to recognize and neutralize the virus. This coordinated response establishes long-term immunological memory, preparing the body to fight off a future infection.
Primary Vaccine Applications
The most established use for MVA is as a vaccine against orthopoxviruses like smallpox and mpox. Marketed under trade names including JYNNEOS in the United States, Imvanex in Europe, and Imvamune in Canada, the MVA-BN vaccine is a standard public health tool. It is approved for use against both smallpox and mpox, and the World Health Organization granted it prequalification status for mpox in 2024.
A primary advantage of the MVA vaccine is its safety profile, making it suitable for a broader population than older smallpox vaccines. Because it is non-replicating, it can be administered to individuals with compromised immune systems, such as those with HIV or skin conditions like eczema. This improved safety also removes the risk of a lesion forming at the injection site, a common occurrence with previous vaccines.
The vaccine is recommended for individuals at high risk of mpox exposure during an outbreak, including close contacts of confirmed cases. It is also used for preventative vaccination for laboratory personnel who work with orthopoxviruses.
Use as a Viral Vector Platform
Beyond its use against poxviruses, MVA serves as a versatile platform for creating vaccines against other diseases. Scientists use its structure as a viral vector, which is a biological delivery vehicle. By inserting a gene from another pathogen, such as a virus or bacterium, into the MVA genome, the virus can be engineered to produce that pathogen’s antigens.
When this engineered MVA is administered, it enters human cells and produces the protein from the inserted gene. The immune system then recognizes this foreign antigen and builds a specific response to it. This method allows MVA to be adapted to teach the immune system how to fight off numerous pathogens by presenting their antigens on a safe viral platform.
MVA-based vaccines are being investigated for diseases like HIV, malaria, influenza, and tuberculosis. There is also exploration into using MVA vectors to create therapeutic cancer vaccines, which would train the immune system to recognize and attack tumor cells. This adaptability makes MVA a valuable tool for developing new vaccines.