Construction Of A Recombinant Vesicular Stomatitis Virus Expressing Zaire Ebola Virus Glycoprotein

Ebola viruses(EBOV) are the causative agents of a severe form of viral haemorrhagic fever inhumans and nonhuman primates, designated Ebola haemorrhagic fever (EHF), with high case fatalityrates of70%-90%。EBOV is one of the most deadly infectious virus currently known to man. EBOV isalso considered to have potential as a biological weapon and is categorized as a Category A bioterrorismagent by the Centers for Disease Control and Prevention. Ebola is mainly endemic in Africa and hascaused severe human and economic losses. EBOV also has the potential to spread to our countryalthough it has never been found yet. It is very urgent to develop a safe and effective vaccine for EBOV.EBOV is a member of the genus Filovirus in the Filoviridae family. It is a RNA virus that containsa single-stranded,negative-sense and non-segmented genome. The Ebola virus is comprised of fourserotypes, Zaire Ebola virus(ZEBOV), Sudan Ebola virus(SEBOV),Reston Ebola virus(REBOV) andCote d’Ivoire Ebola virus(CEBOV). ZEBOV is the most virulent among the four serotypes with highmortality rates up to90%.The glycoprotein (GP) is the only transmembrane protein of Ebola virus andis the major protein inducing protective immunity and neutralizing antibodies in host.VSV as a RNA virus vector has many advantages. VSV’s compact11kb genome can accommodatemaximum4.5kb of foreign gene that are highly expressed in infected cells.VSV is easily manufacturedon a large scale in cell lines already approved for vaccine production. VSV is very sensitive tointerferon and can be cleaned fast.By using VSV reverse genetics system, We constructed and rescued a recombinant vesicularstomatitis virus (rVSV-ZEBOV-GP) which expressed Zaire Ebola virus glycoprotein. The expression ofZEBOV GP in recombinant virus was conformed by western blot and indirect immunofluorescenceassay. The recombinant virus had the similar fast and high titer growth with parent virus. Inoculatedwith mice at maximum dose showed safety in at least one mammal mode. Furthermore, neutralizationtests showed that rVSV-ZEBOV-GP was able to induce neutralizing antibodies against ZEBOV GPpseudotyped VSV. Our data indicated that rVSV-ZEBOV-GP has the potential to be a vaccine candidateagainst Zaire Ebola virus.