Hepatitis b disease and prevention：乙型肝炎疾病预防

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1、UpdateonmalariavaccineMarkR.Withers,M.D.,MPH,Director,WRPKombewaClinicDrWalterOtienoMBChB,M.Med(Paeds),PhDWalterReedProject-CentreforClinicalResearchKenyaMedicalResearchInstitute22WRP-Kisumu3WRP-Kisumu:4maincampusesKisumuHQ(“Kondele”)AdministrationB

2、asicscience:ELISA,PCR,flowcyt,RDTsNewNyanzaProvincialGeneralHospital(PGH,Russian)Children’sHospital:65bedfacilityWard8:dedicatedin-outpatientclinicalresearchcenter“CenterofExcellence”formalariamicroscopyKEMRI“CenterforGlobalHealth”(Kisiantown)Entomol

3、ogymalariaculturelab(monitorsdrugresistancepatterns)KombewaClinicalResearchCenterDedicatedunitforlargeclinicaltrialsWhyismalariasoimportant?Severediseaseburden300-500millioncases575000CM(19%mortality)1.42–5.66millionAnemia(13%mortality)1.12–1.99milli

4、onRDS(18%mortality)InKombewa62%ofadmissionsinchildrenduetomalariaMalariaVaccineDevelopmentOngoingforP.falciparum&P.vivaxTheoreticalConcepts:PregnantwomenprotectnewbornsLivinginendemicareasdevelopimmunityMalariavaccinestargetthelifecycle:Pre-erythrocy

5、ticstage(sporozoite/hepatic)Erythrocytic(asexual)stageSexualstage(transmissionblocking)TARGETSOFMALARIAVACCINESPre-erythrocytic-Preventinfection-ReducediseaseBlood-stage-PreventdiseaseTransmissionblocking-PreventtransmissionRTS,SProgramHistoryCircums

6、porozoiteproteinMostabundantproteincoveringentiresporozoitesurfaceAlsoexpressedbymalarialiverstagesStructureofCSprotein:OfallmalariaspecieshasacentraldomainwithseveralaminoacidrepetitionsAminoacidsequencethatcomposeseachrepetitioniscompletelydifferen

7、tforeachplasmodiumspeciesCircumsporozoiteproteinStructureofCSprotein:P.falciparumCSproteinhaslimitedvariabilitythereforeidealforvaccinesP.vivaxisolatesdisplayenormousvariation-thereforenotidealformalariavaccinesAminoacidrepetitionstargetsforantibodie

8、sN-&C-terminalscontainepitopesrecognizedbyCD4&CD8TcellsTcellsspecificforepitopesofCSproteinconferprotectiveimmunityagainstliverstagesRTS,SMalariaVaccineDevelopmentPre-erythrocyticstagevaccineCompositionofvaccineantigen:Sequenceofcircumsporozoiteprote