Research press release


Nature Medicine

Ebola: Durable immunity generated in non-human primates


N Sullivanたちが、エボラウイルスワクチンを開発するこれまでの試みで数回使われてきたヒトアデノウイルスではなく、チンパンジーアデノウイルスを選んだのは、多くの人がヒトアデノウイルスにすでに曝露されており、そのために免疫系がプライミングされていてウイルスが中和される可能性があるからである。今回のワクチンの前臨床試験は少数のマカクザルを使って行われた。長期的な防御効果は、宿主防御に関係するエフェクターT細胞および記憶T細胞の存在数と相関していた。


Long-term immunity to the highly lethal Zaire ebolavirus (EBOV), which is currently spreading through West Africa, has been induced in macaques using a vaccine based on the chimpanzee-derived adenovirus vector, ChAd3, for which Phase 1 human trials have just been announced. The research, published in Nature Medicine this week, found that a prime-boost vaccine regimen, in which animals are first inoculated with ChAd3 coding for an ebolavirus glycoprotein (GP), and eight weeks later inoculated with a different vector MVA (modified vaccine Ankara) carrying the same gene, is the most effective, although a single shot with the ChAd3 vaccine also provided complete short-term and partial long-term protection. This was the first vaccination regime to be found to provide protection to the virus a full ten months after administration; previous tests challenged animals at only four to five weeks after vaccination.

Nancy Sullivan and colleagues selected chimpanzee adenoviruses rather than human adenoviruses-which have been used in some previous efforts to develop an effective ebolavirus vaccine-because many humans have already been exposed to human adenoviruses and therefore their immune systems are primed to neutralize them. They undertook preclinical trials of these vaccines in a small number of macaques. Long-term protection correlated with the abundance of effector and memory T immune cells, associated with host defense.

Although the macaques were challenged only with EBOV, because the vaccines contained genes coding for the glycoproteins from both EBOV and another commonly occurring ebolavirus species, Sudan ebolavirus (SUDV), it is possible that the vaccine will protect against both strains.

The authors conclude that the rapid-onset vaccine protection with durable immunity could potentially help contain the spread of emerging ebolaviruses.

doi: 10.1038/nm.3702


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