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