Warfield Kelly L, Dye John M, Wells Jay B, Unfer Robert C, Holtsberg Frederick W, Shulenin Sergey, Vu Hong, Swenson Dana L, Bavari Sina, Aman M Javad
Integrated Biotherapeutics, Inc., Gaithersburg, Maryland, United States of America.
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.
PLoS One. 2015 Mar 20;10(3):e0118881. doi: 10.1371/journal.pone.0118881. eCollection 2015.
Filoviruses cause hemorrhagic fever resulting in significant morbidity and mortality in humans. Several vaccine platforms that include multiple virus-vectored approaches and virus-like particles (VLPs) have shown efficacy in nonhuman primates. Previous studies have shown protection of cynomolgus macaques against homologous infection for Ebola virus (EBOV) and Marburg virus (MARV) following a three-dose vaccine regimen of EBOV or MARV VLPs, as well as heterologous protection against Ravn Virus (RAVV) following vaccination with MARV VLPs. The objectives of the current studies were to determine the minimum number of vaccine doses required for protection (using EBOV as the test system) and then demonstrate protection against Sudan virus (SUDV) and Taï Forest virus (TAFV). Using the EBOV nonhuman primate model, we show that one or two doses of VLP vaccine can confer protection from lethal infection. VLPs containing the SUDV glycoprotein, nucleoprotein and VP40 matrix protein provide complete protection against lethal SUDV infection in macaques. Finally, we demonstrate protective efficacy mediated by EBOV, but not SUDV, VLPs against TAFV; this is the first demonstration of complete cross-filovirus protection using a single component heterologous vaccine within the Ebolavirus genus. Along with our previous results, this observation provides strong evidence that it will be possible to develop and administer a broad-spectrum VLP-based vaccine that will protect against multiple filoviruses by combining only three EBOV, SUDV and MARV components.
丝状病毒可引发出血热，导致人类出现显著的发病率和死亡率。包括多种病毒载体方法和病毒样颗粒（VLP）在内的几种疫苗平台已在非人类灵长类动物中显示出有效性。先前的研究表明，在接种三剂埃博拉病毒（EBOV）或马尔堡病毒（MARV）VLP后，食蟹猴可免受EBOV和MARV的同源感染，以及在接种MARV VLP后可获得对拉文病毒（RAVV）的异源保护。当前研究的目的是确定提供保护所需的最低疫苗剂量（以EBOV作为测试系统），然后证明对苏丹病毒（SUDV）和塔伊森林病毒（TAFV）的保护作用。使用EBOV非人类灵长类动物模型，我们表明一剂或两剂VLP疫苗可提供免受致命感染的保护。含有SUDV糖蛋白、核蛋白和VP40基质蛋白的VLP可完全保护猕猴免受致命的SUDV感染。最后，我们证明了EBOV而非SUDV的VLP对TAFV具有介导的保护效力；这是首次在埃博拉病毒属内使用单一组分异源疫苗实现完全的跨丝状病毒保护。连同我们之前的结果，这一观察结果提供了有力证据，表明通过仅组合EBOV、SUDV和MARV三种成分，有可能开发和接种一种基于VLP的广谱疫苗，以预防多种丝状病毒。
