1. Protective Efficacy and Long-Term Immunogenicity in Cynomolgus Macaques by Ebola Virus Glycoprotein Synthetic DNA Vaccines
- Author
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Megan C. Wise, Jean D. Boyer, Gary P. Kobinger, Kaylie N. Tran, Veronica Scott, Alexander Bello, Jonathan Audet, Shane Jones, Emma L. Reuschel, Geoff Soule, Ross Plyler, Kimberly A. Kraynyak, Shihua He, Daniel O. Villarreal, Devon J. Shedlock, Kate E. Broderick, Marc-Antoine de La Vega, Amir S. Khan, Ami Patel, Jian Yan, Dinah Amante, Xiangguo Qiu, Kevin Tierney, Jewell Walters, Trina Racine, Niranjan Y. Sardesai, Daniel H. Park, Gary Wong, David B. Weiner, Amelia A. Keaton, and Karuppiah Muthumani
- Subjects
Male ,0301 basic medicine ,medicine.disease_cause ,Injections, Intramuscular ,Virus ,Viral vector ,DNA vaccination ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Immunity ,Vaccines, DNA ,medicine ,Animals ,Immunology and Allergy ,030212 general & internal medicine ,Ebola Vaccines ,Ebola virus ,business.industry ,Immunogenicity ,Hemorrhagic Fever, Ebola ,Ebolavirus ,Virology ,Vaccination ,Disease Models, Animal ,Macaca fascicularis ,030104 developmental biology ,Infectious Diseases ,Female ,business - Abstract
Background There remains an important need for prophylactic anti-Ebola virus vaccine candidates that elicit long-lasting immune responses and can be delivered to vulnerable populations that are unable to receive live-attenuated or viral vector vaccines. Methods We designed novel synthetic anti-Ebola virus glycoprotein (EBOV-GP) DNA vaccines as a strategy to expand protective breadth against diverse EBOV strains and evaluated the impact of vaccine dosing and route of administration on protection against lethal EBOV-Makona challenge in cynomolgus macaques. Long-term immunogenicity was monitored in nonhuman primates for >1 year, followed by a 12-month boost. Results Multiple-injection regimens of the EBOV-GP DNA vaccine, delivered by intramuscular administration followed by electroporation, were 100% protective against lethal EBOV-Makona challenge. Impressively, 2 injections of a simple, more tolerable, and dose-sparing intradermal administration followed by electroporation generated strong immunogenicity and was 100% protective against lethal challenge. In parallel, we observed that EBOV-GP DNA vaccination induced long-term immune responses in macaques that were detectable for at least 1 year after final vaccination and generated a strong recall response after the final boost. Conclusions These data support that this simple intradermal-administered, serology-independent approach is likely important for additional study towards the goal of induction of anti-EBOV immunity in multiple at-risk populations.
- Published
- 2018