Protective Efficacy and Long-Term Immunogenicity in Cynomolgus Macaques by Ebola Virus Glycoprotein Synthetic DNA Vaccines. (10th October 2018)

• Record Type: Journal Article
• Authors: Patel, Ami; Reuschel, Emma L; Kraynyak, Kimberly A; Racine, Trina; Park, Daniel H; Scott, Veronica L; Audet, Jonathan; Amante, Dinah; Wise, Megan C; Keaton, Amelia A; Wong, Gary; Villarreal, Daniel O; Walters, Jewell; Muthumani, Kar; Shedlock, Devon J; de La Vega, Marc-Antoine; Plyler, Ross; Boyer, Jean; Broderick, Kate E; Yan, Jian; Khan, Amir S; Jones, Shane; Bello, Alexander; Soule, Geoff; Tran, Kaylie N; He, Shihua; Tierney, Kevin; Qiu, Xiangguo; Kobinger, Gary P; Sardesai, Niranjan Y; Weiner, David B;
• Is Part Of: Journal of infectious diseases. Volume 219:Number 4(2019)
• Page Start: 544
• Page End: 555
• Publication Date: 2018-10-10
• Subjects: Ebolavirus -- DNA vaccine -- glycoprotein -- intradermal electroporation -- ID delivery -- protection -- nonhuman primates -- long-term immunogenicity; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiy537
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract : Intradermal delivery of an EBOV-GP DNA vaccine is dose sparing and protective against lethal challenge in macaques and induces durable immune responses. This vaccine is a safe nonlive, temperature stable, serological independent alternative approach for protection of vulnerable populations among others. 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.