Increasing numbers of human cowpox virus
infections that are being observed and that particularly affect young non-vaccinated persons have renewed interest in this
zoonotic disease. Usually causing a self-limiting local
infection, human
cowpox can in fact be fatal for immunocompromised individuals. Conventional
smallpox vaccination presumably protects an individual from
infections with other Orthopoxviruses, including cowpox virus. However, available live
vaccines are causing severe adverse reactions especially in individuals with impaired immunity. Because of a decrease in protective immunity against Orthopoxviruses and a coincident increase in the proportion of immunodeficient individuals in today's population, safer
vaccines need to be developed. Recombinant
subunit vaccines containing cross-reactive
antigens are promising candidates, which avoid the application of infectious virus. However,
subunit vaccines should contain carefully selected
antigens to confer a solid cross-protection against different Orthopoxvirus species. Little is known about the cross-reactivity of
antibodies elicited to cowpox virus
proteins. Here, we first identified 21 immunogenic
proteins of
cowpox and vaccinia virus by serological screenings of genomic Orthopoxvirus expression libraries. Screenings were performed using sera from vaccinated humans and animals as well as clinical sera from patients and animals with a naturally acquired cowpox virus
infection. We further analyzed the cross-reactivity of the identified immunogenic
proteins. Out of 21 identified
proteins 16 were found to be cross-reactive between
cowpox and vaccinia virus. The presented findings provide important indications for the design of new-generation recombinant
subunit vaccines.