DNA-based vaccines have an excellent safety record, are inherently stable, are simple to create, can be manufactured rapidly and do not require cold-chain storage, making this technology attractive for use against bioterrorism threats, emerging infectious diseases or genetically engineered pathogens. Despite these attributes, DNA vaccines have not achieved routine usage in large part due to poor immunogenicity related to ineffective delivery methods. We previously developed and tested a DNA vaccine for the Category A biothreat Lassa virus (LASV). This arenavirus is endemic in West Africa where it infects hundreds of thousands of people each year and can cause a highly lethal hemorrhagic fever. We showed that a codon optimized DNA vaccine for LASV delivered by intradermal electroporation (ID-EP) is completely protective against LASV challenge in both guinea pig and nonhuman primate disease models. Although these results are highly encouraging and the ID-EP technology is a very tolerable delivery method from a patient perspective, improvements are still needed to make the technology suitable for mass vaccination. In this application, we describe technological improvements that we expect will result in better vaccine efficacy and ease of use as compared to our existing delivery platform. We propose to develop novel devices with dual depth and/or multiple EP arrays that can target spatially separated skin areas. We will test the devices using the LASV DNA vaccine by itself or delivered in combination with cytokine adjuvants or with DNA vaccines for two additional arenaviruses. Our main goals are: 1) Develop automated, multi-head ID/EP devices able to deliver multiple products to discreet sites simultaneously and/or target different compartments of the skin;2) Determine the affect of co-administering the LASV DNA vaccine with plasmids encoding molecular adjuvants delivered with the novel ID-EP devices;and, 3) Assess the ability of the multi-array ID-EP devices to effectively deliver multiagent arenavirus vaccines. Accomplishment of these goals will not only fill a critical biodefense and public health gap with respect to medical countermeasures against LASV, but will also advance the DNA vaccine field in general by providing a highly tolerable mass vaccination method amenable to multiagent vaccine delivery.

Public Health Relevance

This application seeks to further the preclinical development of a DNA-based vaccine delivery platform including integrated and automated intradermal electroporation delivery. First-of-their-kind devices will be engineered and tested with a vaccine against Lassa virus, a Category A pathogen. The improved vaccine platform will be suitable for mass vaccination using multiagent vaccines.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Special Emphasis Panel (ZAI1-SM-M (J1))
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Repik, Patricia M
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Geneva Foundation
United States
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Cashman, Kathleen A; Wilkinson, Eric R; Wollen, Suzanne E et al. (2017) DNA vaccines elicit durable protective immunity against individual or simultaneous infections with Lassa and Ebola viruses in guinea pigs. Hum Vaccin Immunother 13:3010-3019