医学免疫学课件：Ebola Vaccine

1、Ebola VaccineCONTENTS1Introduction1.1 Epidemiology1.2 Species1.3 Features2Pathogenesis&Treatment3Vaccines3.1 rVSV3.2 ChAd33.3 EBOVVP30 4Summary 1IntroductionEpidemiologyEbola virus disease (EVD)first identified in 1976 in Central Africa19762013: WHOreports a total of 24 outbreaks involving 1716 case

2、s20142016: the largest outbreak in West Africa with 28616 cases and 11310 deathsFigure: /wiki/File:EbolaSubmit2.pngEbola VirusFive speciesZaire, Bundibugyo, Sudan, Reston and Ta ForestPathogenic characteristicsStructureanegative-senseRNA genomeviral envelope, matrix, and nucleocapsid components 80nm

3、in diameter, 800 1000nm longGenome3 leader NP VP35 VP40 GP/sGP VP30 VP24 L trailer 5 2Pathogenesis & TreatmentPathogenesisTreatment 3VaccineVaccineTraditional vaccineInactivated vaccineLive attenuated vaccine: EBOVVP30 New generation vaccineSubunitRecombinantVector: rVSV、ChAd3DNA vaccinationFigure:/

4、wiki/Vaccine#/media/File:Vaccine.pngVaccine-rVSVRecombinant Vesicular Stomatitis Virus (rVSV) vaccineattenuatedreplication-competentgenetically engineeredreplace the VSV glycoprotein with the glycoprotein from a Zaire strain of Ebola virusPreclinical testing (cynomolgus macaques)a single administrat

5、ion: high protectionsupport a pan-firoviruspostexposure prophylaxis: protectionVaccine-rVSVVaccine-rVSVEbola virus disease (EVD)Vaccine-rVSVVaccine-ChAd3rAdChAdChAd3 & ChAd63Chimpanzee adenovirus (ChAd) vaccinereplication-defective genetically engineeredexpressing GPs from EBOV (monovalent) or from

6、EBOV plus SUDV (bivalent)single-inoculation or prime-boost Vaccine-ChAd3Vaccine-ChAd3Vaccine-ChAd3Vaccine-ChAd3Vaccine-ChAd3Vaccine-EBOVVP30 EBOVVP30replication-defectivelive attenuated: gamma-irradiated or H2O2-treated genetically engineeredlacks the coding region for the essential viral transcript

7、ion activator, VP30 prime-boost: full protection in mice and guinea pigsVaccine-EBOVVP30 Vaccine-EBOVVP30 Vaccine-EBOVVP30 Ebola virus disease (EVD)4SummarySummary Vaccine Dose Security rVSVChAd3EBOVVP30Summary Always think new!References1 程颖, 刘军, 李昱,等. 埃博拉病毒病:病原学、致病机制、治疗与疫苗研究进展J. 科学通报, 2014(30):288

8、9-2899.2 Klenk H D, Feldmann H. Ebola and Marburg viruses: molecular and cellular biology.J. Ebola & Marburg Viruses Molecular & Cellular Biology, 2004.3 Rivera A, Messaoudi I. Molecular mechanisms of Ebola pathogenesis.J. Journal of Leukocyte Biology, 2016, 100(5).4 Bradfute S B. The early clinical

9、 development of Ebola virus treatmentsJ. 2016.5刘迎恩, 左朋礼, 孙治刚. 埃博拉病毒疫苗和药物治疗研究进展J. 中华传染病杂志, 2016, 34(6):371-374.6 Regules J A, Beigel J H, Paolino K M, et al. A Recombinant Vesicular Stomatitis Virus Ebola Vaccine - Preliminary Report.J. New England Journal of Medicine, 2015.7 Stanley D A, Honko A N,

10、Asiedu C, et al. Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge.J. Nature Medicine, 2014, 20(10):1126-1129.8 Marzi A, Halfmann P, Hillbatorski L, et al. An Ebola whole-virus vaccine is protective in nonhuman primatesJ. Science, 2015, 348(62

11、33):439-42.9 Geisbert T W, Geisbert J B, Leung A, et al. Single-injection vaccine protects nonhuman primates against infection with marburg virus and three species of ebola virus.J. Journal of Virology, 2009, 83(14):7296-304.10 Henaorestrepo A M, Longini I M, Egger M, et al. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea rin