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

Autor:	Patel A; The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania., Reuschel EL; The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania., Kraynyak KA; Inovio Pharmaceuticals Inc., Plymouth Meeting, Pennsylvania., Racine T; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.; Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada., Park DH; The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania., Scott VL; College of Osteopathic Medicine, William Carey University, Hattiesburg, Mississippi., Audet J; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.; Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada., Amante D; Inovio Pharmaceuticals Inc., Plymouth Meeting, Pennsylvania., Wise MC; Inovio Pharmaceuticals Inc., Plymouth Meeting, Pennsylvania., Keaton AA; The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania., Wong G; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada., Villarreal DO; University of Pennsylvania, Philadelphia., Walters J; Inovio Pharmaceuticals Inc., Plymouth Meeting, Pennsylvania., Muthumani K; The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania., Shedlock DJ; University of Pennsylvania, Philadelphia., de La Vega MA; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada., Plyler R; University of Pennsylvania, Philadelphia., Boyer J; Inovio Pharmaceuticals Inc., Plymouth Meeting, Pennsylvania., Broderick KE; Inovio Pharmaceuticals Inc., Plymouth Meeting, Pennsylvania., Yan J; Inovio Pharmaceuticals Inc., Plymouth Meeting, Pennsylvania., Khan AS; Inovio Pharmaceuticals Inc., Plymouth Meeting, Pennsylvania., Jones S; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada., Bello A; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada., Soule G; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada., Tran KN; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada., He S; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada., Tierney K; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada., Qiu X; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.; Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada., Kobinger GP; University of Pennsylvania, Philadelphia.; Université Laval, Québec, Canada., Sardesai NY; Inovio Pharmaceuticals Inc., Plymouth Meeting, Pennsylvania., Weiner DB; The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2019 Jan 29; Vol. 219 (4), pp. 544-555.
DOI:	10.1093/infdis/jiy537
Abstrakt:	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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu