title: Multivalent smallpox DNA vaccine delivered by intradermal electroporation drives protective immunity in nonhuman primates against lethal monkeypox challenge.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Hirao
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Draghia-Akli
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Prigge
authors.forename: Maria
authors.initials: M
authors.lastname: Yang
authors.forename: Abhishek
authors.initials: A
authors.lastname: Satishchandran
authors.forename: Ling
authors.initials: L
authors.lastname: Wu
authors.forename: Erika
authors.initials: E
authors.lastname: Hammarlund
authors.forename: Amir S
authors.initials: AS
authors.lastname: Khan
authors.forename: Tahar
authors.initials: T
authors.lastname: Babas
authors.forename: Lowrey
authors.initials: L
authors.lastname: Rhodes
authors.forename: Peter
authors.initials: P
authors.lastname: Silvera
authors.forename: Mark
authors.initials: M
authors.lastname: Slifka
authors.forename: Niranjan Y
authors.initials: NY
authors.lastname: Sardesai
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018274:Electroporation / Q000379:methods; D006801:Humans; D008253:Macaca mulatta; D045908:Mpox, Monkeypox / Q000517:prevention & control*; D012900:Smallpox Vaccine / Q000008:administration & dosage / Q000276:immunology*; D016019:Survival Analysis; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D012900:Smallpox Vaccine; D019444:Vaccines, DNA