The threat of a
smallpox-based bioterrorist event or a human
monkeypox outbreak has heightened the importance of new, safe
vaccine approaches for these pathogens to
complement older poxviral
vaccine platforms. As poxviruses are large, complex viruses, they present technological challenges for simple
recombinant vaccine development where a multicomponent mixtures of
vaccine antigens are likely important in protection. We report that a synthetic, multivalent, highly concentrated,
DNA vaccine delivered by a minimally invasive, novel skin electroporation microarray can drive polyvalent immunity in macaques, and offers protection from a highly pathogenic
monkeypox challenge. Such a diverse, high-titer antibody response produced against 8 different
DNA-encoded
antigens delivered simultaneously in microvolumes has not been previously described. These studies represent a significant improvement in the efficiency of the
DNA vaccine platform, resulting in immune responses that mimic live
viral infections, and would likely have relevance for
vaccine design against complex human and animal pathogens.