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 smallpox vaccines derived from other poxviruses. 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 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) 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,