Understanding orthopoxvirus interference with host immune responses to inform novel vaccine design

Jenner's original vaccine used cowpox virus. Cowpox virus and, subsequently, vaccinia virus, a closely related Orthopoxvirus, provided the means to eradicate smallpox. This history and the unique properties of the virus suggest that vaccinia virus will continue to provide a useful vaccine platform. Yet, surprisingly, it has become apparent that much of the virus genome encodes accessory proteins that interfere with host immune responses to infection. Manipulation of these genes offers the potential for new generations of orthopoxvirus vaccines in which we will have far greater control over key features of the vaccination, including the sites of virus infection, the degree of virus replication, the pathogenicity of the virus and, most importantly, the suppression or induction of immune responses of specific types.