Adaptive immunity to vaccinia virus: Revisiting an old friend

The study of immunity to vaccinia virus has had a renaissance in recent years, largely owing to a desire to produce a safe and efficacious vaccine against smallpox in the context of biodefense concerns. This review focuses on three areas that have seen recent advances: the mapping of epitopes, data from the clinic (including efforts to determine the longevity of responses in humans and recent smallpox vaccine trials) and the use of animal models to determine the requisites for successful immunity and the effect of vaccinia virus immunomodulators on adaptive immune responses. This is intended to be a snapshot of areas generating current interest rather than a comprehensive review, and each area is discussed in terms of current achievements and challenges for the future.