Gene Gun-delivered Dna Vaccines for Hemorrhagic Fever with Renal Syndrome: Advancement to Clinical Trials

We developed a DNA vaccine to protect against hemorrhagic fever with renal syndrome (HFRS). The vaccine consists of two plasmid DNAs that produce immunogenic proteins of two of the four etiologic agents of HFRS, Hantaan, and Puumala viruses. The DNA is precipitated onto micrometer-sized gold beads and delivered to the skin of animals or human volunteers using a hand-held disposable “gene gun.” We showed that these DNA vaccines elicited high levels of antiviral neutralizing antibodies and protected animals from challenge with all four HFRS-causing viruses. We assessed the safety of the gene gun-delivered DNAs in animals using Good Laboratory Practices (GLP). Rigorous statistical analyses indicated that there were no significant differences between vaccinated and control animals. To demonstrate potency and stability of the vaccines, we developed a rapid, reliable, and sensitive flow-cytometric assay. The assay was adapted to fit within a standard operating procedure (SOP) for regulation under GLP guidelines. Safety and potency results were submitted to the U.S. Food and Drug Administration and after their review, a Phase 1 clinical study in 27 volunteers was initiated. This DNA-gene gun vaccine study is the first of its kind to be performed by the U.S. military, and if successful, will introduce a technology that could be applied for developing vaccines for many endemic diseases or bioterrorism pathogens that threaten troops.