Immune protection of nonhuman primates against Ebola virus with single low-dose adenovirus vectors encoding modified GPs

使用编码修饰 GP 的单个低剂量腺病毒载体对非人灵长类动物进行针对埃博拉病毒的免疫保护

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作者:Nancy J Sullivan, Thomas W Geisbert, Joan B Geisbert, Devon J Shedlock, Ling Xu, Laurie Lamoreaux, Jerome H H V Custers, Paul M Popernack, Zhi-Yong Yang, Maria G Pau, Mario Roederer, Richard A Koup, Jaap Goudsmit, Peter B Jahrling, Gary J Nabel

Background

Ebola virus causes a hemorrhagic fever syndrome that is associated with high mortality in humans. In the absence of effective therapies for Ebola virus infection, the development of a vaccine becomes an important strategy to contain outbreaks. Immunization with DNA and/or replication-defective adenoviral vectors (rAd) encoding the Ebola glycoprotein (GP) and nucleoprotein (NP) has been previously shown to confer specific protective immunity in nonhuman primates. GP can exert cytopathic effects on transfected cells in vitro, and multiple GP forms have been identified in nature, raising the question of which would be optimal for a human vaccine.

Conclusions

Expression of specific GPs alone vectored by rAd are sufficient to confer protection against lethal challenge in a relevant nonhuman primate model. Elimination of NP from the vaccine and dose reductions to 10(10) rAd particles do not diminish protection and simplify the vaccine, providing the basis for selection of a human vaccine candidate.

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