A vaccinia virus renaissance New vaccine and immunotherapeutic uses after smallpox eradication

In 1796, Edward Jenner introduced the concept of vaccination with cowpox virus, an Orthopoxvirus within the family Poxviridae that elicits cross protective immunity against related orthopoxviruses, including smallpox virus (variola virus). Over time, vaccinia virus (VAC V) replaced cowpox virus as the smallpox vaccine, and vaccination efforts eventually led to the global eradication of smallpox in 1979. VAC V has many characteristics that make it an excellent vaccine and that were crucial for the successful eradication of smallpox, including (1) its exceptional thermal stability (a very important but uncommon characteristic in live vaccines), (2) its ability to elicit strong humoral and cell-mediated immune responses, (3) the fact that it is easy to propagate and (4) that it is not oncogenic, given that VAC V replication occurs exclusively within the host cell cytoplasm and there is no evidence that the viral genome integrates into the host genome. Since the eradication of smallpox, VAC V has experienced a renaissance of interest as a viral vector for the development of recombinant vaccines, immunotherapies and oncolytic therapies, as well as the development of next-generation smallpox vaccines. This revival is mainly due to the successful use and extensive characterization of VAC V as a vaccine during the smallpox eradication campaign, along with the ability to genetically manipulate its large dsDNA genome while retaining infectivity and immunogenicity, its wide mammalian host range, and its natural tropism for tumor cells that allows its use as an oncolytic vector. This review provides an overview of new uses of VAC V that are currently being explored for the development of vaccines, immunotherapeutics and oncolytic virotherapies.