Hepatitisbdiseaseandprevention乙型肝炎疾病预防.pptx

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1、11WRP-Kisumu第1页/共25页2WRP-Kisumu:4 main campuses Kisumu HQ (“Kondele”)Administration Basic science:ELISA,PCR,flow cyt,RDTsNew Nyanza Provincial General Hospital(PGH,Russian)Childrens Hospital:65 bed facilityWard 8:dedicated in-out patient clinical research center“Center of Excellence”for malaria micr

2、oscopy KEMRI“Center for Global Health”(Kisian town)Entomologymalaria culture lab(monitors drug resistance patterns)Kombewa Clinical Research CenterDedicated unit for large clinical trials第2页/共25页Malaria Vaccine Development Ongoing for P.falciparum&P.vivaxTheoretical Concepts:Pregnant women protect n

3、ewbornsLiving in endemic areas develop immunity Malaria vaccines target the life cycle:Pre-erythrocytic stage(sporozoite/hepatic)Erythrocytic(asexual)stageSexual stage(transmission blocking)第4页/共25页TARGETS OF MALARIA VACCINES Pre-erythrocytic-Prevent infection-Reduce diseaseBlood-stage-Prevent disea

4、seTransmission blocking-Prevent transmission第5页/共25页第6页/共25页第7页/共25页RTS,S Program History第8页/共25页Circumsporozoite proteinMost abundant protein covering entire sporozoite surfaceAlso expressed by malaria liver stagesStructure of CS protein:Of all malaria species has a central domain with several amin

5、o acid repetitionsAmino acid sequence that composes each repetition is completely different for each plasmodium species第9页/共25页Circumsporozoite protein Structure of CS protein:P.falciparum CS protein has limited variability therefore ideal for vaccinesP.vivax isolates display enormous variation-ther

6、efore not ideal for malaria vaccinesAmino acid repetitions targets for antibodies N-&C-terminals contain epitopes recognized by CD4&CD8 T cells T cells specific for epitopes of CS protein confer protective immunity against liver stages第10页/共25页RTS,S Malaria Vaccine DevelopmentPre-erythrocytic stage

7、vaccineComposition of vaccine antigen:Sequence of circumsporozoite protein Hepatitis B surface antigen(HBsAg)Adjuvants:ASO2&ASO1HBsAg is encoded with hepatitis B virus S protein gene,therefore protects against hepatitis B.第11页/共25页RTS,S Malaria Vaccine DevelopmentGoal:develop 80%efficacious vaccine

8、by 2025 with 4 year protection Characteristics of an ideal vaccine:Safe Effective Affordable Easy to deliver(EPI delivery system)Will not interfere with other EPI vaccines 第12页/共25页DEVELOPMENT OF THE RTS,S MALARIA VACCINESPOROZOITE STAGE OF MALARIA PARASITE第13页/共25页DEVELOPMENT OF RTS,S MALARIA VACCI

9、NE R(REPEAT)+S(HEP-B)+T(T-CELL)R T SSSPOROZOITEHEP-B VIRUS第14页/共25页STRUCTURE OF THE CIRCUMSPOROZOITE PROTEIN(CSP)CENTRAL REPEAT REGIONN-TERMINALC-TERMINALT-CELL EPITOPES第15页/共25页DEVELOPMENT OF RTS,S MALARIA VACCINE SPOROZOITES ARE COATED WITH A SURFACE PROTEIN CIRCUMSPOROZOITE PROTEIN(CSP)A SEGMENT

10、OF THE CIRCUMSPOROZOITE PROTEIN CONTAINING REPEAT(R)AND T-CELL EPITOPES(T)IS FUSED TO HEPATITIS B SURFACE ANTIGEN(S)TO PRODUCE FUSION PROTEIN,RTS RTS IS COMBINED WITH A SECOND UNFUSED HEPATITIS B SEGMENT(S)TO FORM A STABLE RTS,S ANTIGEN 第16页/共25页RESULTS OF RTS,S MALARIA VACCINE TRIALSMany trials hav

11、e shown that RTS,S malaria vaccine is safe and immunogenicRTS,S efficacy trial in Mozambique enrolled 2022 children aged 1-4 years50%protection against severe malaria and severe anemia at 42 months post vaccination第17页/共25页RESULTS OF RTS,S MALARIA VACCINE TRIALSMany trials have shown that RTS,S mala

12、ria vaccine is safe and stimulates the immune systemRTS,S efficacy trial in Mozambique enrolled 2022 children aged 1-4 years50%protection against severe malaria and severe anemiaMalaria causes 1 million childhood deaths per year in Africa If this vaccine could reduce by half the cases of severe dise

13、ase,we would be saving thousands of lives第18页/共25页第19页/共25页MAIN OBJECTIVES To investigate efficacy against clinical disease in children 5-17 months of age and Infants 6-12 weeks of age who receive the vaccine co-administered with EPI vaccines 第20页/共25页ON GOING RTS,S VACCINE TRIALA multi-center,Phase

14、 III trial of the candidate malaria vaccine RTS,SThe trial has been designed to address key safety and efficacy information required before a vaccine can be licensed Across 11 sites in Africa with different levels of malaria transmission;Kenya,Tanzania,Mozambique,Gabon,Ghana,Burkina Faso第21页/共25页How

15、 does RTS,S work?RTS,S induces the production of antibodies and T cells that are believed to diminish the malaria parasites ability to infect,develop,and survive in the human liver.第22页/共25页DESIGN OF THE TRIALVaccination at 0,1,2 monthsBoost at month 20RTS,SRTS,SRTS,SControl VaccineControl vaccineControl VaccineVaccination at 0,1,2 monthsBoost at month 20RTS,S+EPI VACCINE RTS,SRTS,S/AS01E+EPI VACCINECONTROL VACCINECONTROL VACCINE +EPI VACCINE CONTROL VACCINEChildren 6-12 weeks of ageChildren 5-17 months of age 第23页/共25页Thank you第24页/共25页