Protective Efficacy and Long-Term Immunogenicity in Cynomolgus Macaques by Ebola Virus Glycoprotein Synthetic DNA Vaccines

Ami Patel, Emma L. Reuschel, Kimberly A. Kraynyak, Trina Racine, Daniel H. Park, Veronica L. Scott, Jonathan Audet, Dinah Amante, Megan C. Wise, Amelia A. Keaton, Gary Wong, Daniel O. Villarreal, Jewell Walters, Kar Muthumani, Devon J. Shedlock, Marc Antoine De La Vega, Ross Plyler, Jean Boyer, Kate E. Broderick, Jian YanAmir S. Khan, Shane Jones, Alexander Bello, Geoff Soule, Kaylie N. Tran, Shihua He, Kevin Tierney, Xiangguo Qiu, Gary P. Kobinger, Niranjan Y. Sardesai, David B. Weiner

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)544-555
Number of pages12
JournalJournal of Infectious Diseases
Volume219
Issue number4
StatePublished - Jan 29 2019
Externally publishedYes

Keywords

  • DNA vaccine
  • Ebolavirus
  • ID delivery
  • glycoprotein
  • intradermal electroporation
  • long-term immunogenicity
  • nonhuman primates
  • protection

ASJC Scopus subject areas

  • General Medicine

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