Mire Chad E, Geisbert Joan B, Agans Krystle N, Satterfield Benjamin A, Versteeg Krista M, Fritz Elizabeth A, Feldmann Heinz, Hensley Lisa E, Geisbert Thomas W
Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, United States of America; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
PLoS One. 2014 Apr 23;9(4):e94355. doi: 10.1371/journal.pone.0094355. eCollection 2014.
The filoviruses, Marburg virus (MARV) and Ebola virus, causes severe hemorrhagic fever with high mortality in humans and nonhuman primates. A promising filovirus vaccine under development is based on a recombinant vesicular stomatitis virus (rVSV) that expresses individual filovirus glycoproteins (GPs) in place of the VSV glycoprotein (G). These vaccines have shown 100% efficacy against filovirus infection in nonhuman primates when challenge occurs 28-35 days after a single injection immunization. Here, we examined the ability of a rVSV MARV-GP vaccine to provide protection when challenge occurs more than a year after vaccination. Cynomolgus macaques were immunized with rVSV-MARV-GP and challenged with MARV approximately 14 months after vaccination. Immunization resulted in the vaccine cohort of six animals having anti-MARV GP IgG throughout the pre-challenge period. Following MARV challenge none of the vaccinated animals showed any signs of clinical disease or viremia and all were completely protected from MARV infection. Two unvaccinated control animals exhibited signs consistent with MARV infection and both succumbed. Importantly, these data are the first to show 100% protective efficacy against any high dose filovirus challenge beyond 8 weeks after final vaccination. These findings demonstrate the durability of VSV-based filovirus vaccines.
丝状病毒，如马尔堡病毒（MARV）和埃博拉病毒，可导致人类和非人灵长类动物出现严重出血热，死亡率很高。一种正在研发的有前景的丝状病毒疫苗是基于重组水泡性口炎病毒（rVSV），该病毒表达单个丝状病毒糖蛋白（GPs）以替代VSV糖蛋白（G）。当在单次注射免疫后28 - 35天进行攻毒时，这些疫苗在非人灵长类动物中对丝状病毒感染显示出100%的有效性。在此，我们研究了rVSV MARV - GP疫苗在接种疫苗一年多后进行攻毒时提供保护的能力。食蟹猴用rVSV - MARV - GP进行免疫，并在接种疫苗约14个月后用MARV进行攻毒。免疫导致六只动物的疫苗组在整个攻毒前期都具有抗MARV GP IgG。在接受MARV攻毒后，没有一只接种疫苗的动物表现出任何临床疾病或病毒血症的迹象，并且所有动物都完全受到保护，免受MARV感染。两只未接种疫苗的对照动物表现出与MARV感染一致的症状，并且都死亡了。重要的是，这些数据首次表明在最后一次接种疫苗8周后，对任何高剂量丝状病毒攻毒具有100%的保护效力。这些发现证明了基于VSV的丝状病毒疫苗的持久性。
