2区 · 医学
Article
作者: Shedlock, Devon J ; Tran, Kaylie N ; Plyler, Ross ; de La Vega, Marc-Antoine ; Villarreal, Daniel O ; Wong, Gary ; Soule, Geoff ; Jones, Shane ; Broderick, Kate E ; Reuschel, Emma L ; Keaton, Amelia A ; Kobinger, Gary P ; Weiner, David B ; Audet, Jonathan ; Racine, Trina ; Boyer, Jean ; Muthumani, Kar ; Khan, Amir S ; Sardesai, Niranjan Y ; Patel, Ami ; He, Shihua ; Yan, Jian ; Tierney, Kevin ; Amante, Dinah ; Qiu, Xiangguo ; Walters, Jewell ; Scott, Veronica L ; Park, Daniel H ; Wise, Megan C ; Kraynyak, Kimberly A ; Bello, Alexander
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.