Jones Steven M, Feldmann Heinz, Ströher Ute, Geisbert Joan B, Fernando Lisa, Grolla Allen, Klenk Hans-Dieter, Sullivan Nancy J, Volchkov Viktor E, Fritz Elizabeth A, Daddario Kathleen M, Hensley Lisa E, Jahrling Peter B, Geisbert Thomas W
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba R3E 3R2, Canada.
Nat Med. 2005 Jul;11(7):786-90. doi: 10.1038/nm1258. Epub 2005 Jun 5.
Vaccines and therapies are urgently needed to address public health needs stemming from emerging pathogens and biological threat agents such as the filoviruses Ebola virus (EBOV) and Marburg virus (MARV). Here, we developed replication-competent vaccines against EBOV and MARV based on attenuated recombinant vesicular stomatitis virus vectors expressing either the EBOV glycoprotein or MARV glycoprotein. A single intramuscular injection of the EBOV or MARV vaccine elicited completely protective immune responses in nonhuman primates against lethal EBOV or MARV challenges. Notably, vaccine vector shedding was not detectable in the monkeys and none of the animals developed fever or other symptoms of illness associated with vaccination. The EBOV vaccine induced humoral and apparent cellular immune responses in all vaccinated monkeys, whereas the MARV vaccine induced a stronger humoral than cellular immune response. No evidence of EBOV or MARV replication was detected in any of the protected animals after challenge. Our data suggest that these vaccine candidates are safe and highly efficacious in a relevant animal model.
迫切需要疫苗和疗法来满足由新兴病原体和生物威胁因子(如丝状病毒埃博拉病毒(EBOV)和马尔堡病毒(MARV))引发的公共卫生需求。在此,我们基于表达EBOV糖蛋白或MARV糖蛋白的减毒重组水疱性口炎病毒载体,开发了针对EBOV和MARV的具有复制能力的疫苗。单次肌肉注射EBOV或MARV疫苗能在非人灵长类动物中引发完全保护性免疫反应,使其免受致死性EBOV或MARV攻击。值得注意的是,在猴子中未检测到疫苗载体脱落,且没有动物出现与接种疫苗相关的发热或其他疾病症状。EBOV疫苗在所有接种疫苗的猴子中诱导了体液免疫和明显的细胞免疫反应,而MARV疫苗诱导的体液免疫反应比细胞免疫反应更强。在攻击后,未在任何受保护动物中检测到EBOV或MARV复制的证据。我们的数据表明,这些候选疫苗在相关动物模型中是安全且高效的。