Immunization with a single extracellular enveloped virus protein produced in bacteria provides partial protection from a lethal orthopoxvirus infection in a natural host.

Subunit vaccines that use the vaccinia virus extracellular envelope protein A33R alone or combined with other structural proteins are excellent candidates for a new smallpox vaccine. Since a new smallpox vaccine would be used in humans, who are the natural hosts for the Orthopoxvirus variola, the agent of smallpox, it would be important to determine whether a prospective smallpox vaccine can protect from a lethal Orthopoxvirus infection in a natural host. We addressed this question using the mouse-specific Orthopoxvirus ectromelia virus. We demonstrate that immunization with recombinant ectromelia virus envelope protein EVM135 or its ortholog vaccinia virus A33R produced in E. coli protects susceptible mice from a lethal ectromelia virus infection. This is the first report that a subunit vaccine can provide protection to a lethal Orthopoxvirus infection in its natural host.