Geisbert Thomas W, Jones Steven, Fritz Elizabeth A, Shurtleff Amy C, Geisbert Joan B, Liebscher Ryan, Grolla Allen, Ströher Ute, Fernando Lisa, Daddario Kathleen M, Guttieri Mary C, Mothé Bianca R, Larsen Tom, Hensley Lisa E, Jahrling Peter B, Feldmann Heinz
Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
PLoS Med. 2005 Jun;2(6):e183. doi: 10.1371/journal.pmed.0020183. Epub 2005 Jun 28.
Recent importation of Lassa fever into Germany, the Netherlands, the United Kingdom, and the United States by travelers on commercial airlines from Africa underscores the public health challenge of emerging viruses. Currently, there are no licensed vaccines for Lassa fever, and no experimental vaccine has completely protected nonhuman primates against a lethal challenge.
We developed a replication-competent vaccine against Lassa virus based on attenuated recombinant vesicular stomatitis virus vectors expressing the Lassa viral glycoprotein. A single intramuscular vaccination of the Lassa vaccine elicited a protective immune response in nonhuman primates against a lethal Lassa virus challenge. Vaccine shedding was not detected in the monkeys, and none of the animals developed fever or other symptoms of illness associated with vaccination. The Lassa vaccine induced strong humoral and cellular immune responses in the four vaccinated and challenged monkeys. Despite a transient Lassa viremia in vaccinated animals 7 d after challenge, the vaccinated animals showed no evidence of clinical disease. In contrast, the two control animals developed severe symptoms including rashes, facial edema, and elevated liver enzymes, and ultimately succumbed to the Lassa infection.
Our data suggest that the Lassa vaccine candidate based on recombinant vesicular stomatitis virus is safe and highly efficacious in a relevant animal model that faithfully reproduces human disease.
近期,从非洲乘坐商业航班的旅行者将拉沙热输入德国、荷兰、英国和美国,这凸显了新兴病毒对公共卫生的挑战。目前,尚无获批的拉沙热疫苗,且尚无实验性疫苗能完全保护非人灵长类动物免受致死性攻击。
我们基于表达拉沙病毒糖蛋白的减毒重组水疱性口炎病毒载体,研发了一种具有复制能力的拉沙病毒疫苗。对非人灵长类动物进行一次肌肉注射拉沙疫苗后,可引发针对致死性拉沙病毒攻击的保护性免疫反应。在猴子中未检测到疫苗传播,且无动物出现与接种相关的发热或其他疾病症状。拉沙疫苗在四只接种并接受攻击的猴子中诱导了强烈的体液免疫和细胞免疫反应。尽管接种动物在攻击后7天出现短暂的拉沙病毒血症,但未出现临床疾病迹象。相比之下,两只对照动物出现了严重症状,包括皮疹、面部水肿和肝酶升高,最终死于拉沙感染。
我们的数据表明,基于重组水疱性口炎病毒的拉沙疫苗候选物在忠实地再现人类疾病的相关动物模型中是安全且高效的。