展开理想的翅膀 让梦想照进现实
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展开理想的翅膀 让梦想照进现实. Sidong Xiong, Ph.D. 0512-65113488 [email protected]. Oct 26, 2011 Suzhou, China. 故 事 缘 起. 1981~1984 (卫生防疫站, CDC ) ??乙型肝炎 ?? 子宫颈癌. 故 事 展 开. 1984 年 师从著名的微生物学家 王言贵 教授 乙型肝炎发病机制的研究 乙型肝炎的动物模型 土拨鼠( woodchuck 、 groundhog )模型. 另 辟 蹊 径. - PowerPoint PPT PresentationTRANSCRIPT
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故 事 缘 起故 事 缘 起
1981~19841981~1984 (卫生防疫(卫生防疫站,站, CDCCDC ))
???? 乙型肝炎乙型肝炎
?? ?? 子宫颈癌子宫颈癌
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故 事 展 开故 事 展 开
19841984 年 师从著名的微生物学家 王言贵 教年 师从著名的微生物学家 王言贵 教授授
乙型肝炎发病机制的研究乙型肝炎发病机制的研究
乙型肝炎的动物模型乙型肝炎的动物模型
土拨鼠(土拨鼠( woodchuckwoodchuck 、、 groundhoggroundhog )模型)模型
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另 辟 蹊 径另 辟 蹊 径
19851985 年 中国医学科学院(协和医科大学)林玉纯 教授年 中国医学科学院(协和医科大学)林玉纯 教授
德国癌症研究中心德国癌症研究中心 Harald zur HausenHarald zur Hausen
子宫颈癌病毒病因学研究子宫颈癌病毒病因学研究
PapilomavirusPapilomavirus
Multiple genotypesMultiple genotypes (( warts, cervical cancerwarts, cervical cancer ))
Antibody-based genotypingAntibody-based genotyping
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另 辟 蹊 径另 辟 蹊 径
子宫颈癌病毒病因学研究子宫颈癌病毒病因学研究
Viral genome specific antibody genotypingViral genome specific antibody genotyping
cancer high risk viral genotypecancer high risk viral genotype
DNA without immunnogenecityDNA without immunnogenecity
(Unable to induce antibody production) (Unable to induce antibody production)
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另 辟 蹊 径另 辟 蹊 径
子宫颈癌病毒病因学研究子宫颈癌病毒病因学研究
Molecular Epidemiology study Molecular Epidemiology study
A new genotype of HPV was found in ChinaA new genotype of HPV was found in China
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深 径 探 幽深 径 探 幽
HumanHuman PapilomavirusPapilomavirus
Warts Warts ??
Cervical cancerCervical cancer ??
MechanismsMechanisms
VirusVirus
Host Host
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深 径 探 幽深 径 探 幽
19891989 师从 著名的免疫学家 林飞卿 教授师从 著名的免疫学家 林飞卿 教授
抗病毒免疫的细胞与分子机制抗病毒免疫的细胞与分子机制
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老 树 新 花 老 树 新 花
HBV : WORLDWIDE HEALTH PROBLEM
WORLD350 MILLION PEOPLE INFECTED 240 MILLION ETHNICALLY CHINESE1 MILLION DEATHS ANNUALLY400 MILLION BY THE YEAR 2000
CHINA 130 MILLION INFECTED POPULATION10% CHRONIC CARRIERS
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老 树 新 花老 树 新 花
19901990 师从著名的病毒学家 闻玉梅 院士师从著名的病毒学家 闻玉梅 院士
乙肝病毒感染慢性化机制及防治策略研究乙肝病毒感染慢性化机制及防治策略研究
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CTLCTL
HBV DNA
HBsAgHBeAg
ALT
Anti-HBs
Anti-HBe
Anti-HBc
ACUTE HEPATITIS BACUTE HEPATITIS B
CHRONIC HEPATITIS BCHRONIC HEPATITIS B
(W)0 4 8 12 16 20 24
ALT
HBV DNA
HBsAgHBeAg
Anti-HBcAnti-HBe
0 1 2 3 4 5 6 (M) 1 2 3 4 5 6 7 8 9 10 (Y)
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0 3 6 9 12 15 18 21 24 27 300
25
50
75
100HealthycarrierCHB
month
anti
-HB
s p
osi
tive
rat
e (%
)
Anti-HBs seroconversion after vaccination with conventional protein HBV vaccine
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HBVHBV
• HBV PERSISTENT INFECTIONHBV PERSISTENT INFECTION• NO SPECIFIC IMMUNORESPONSENO SPECIFIC IMMUNORESPONSE
IMMUNE TOLERANCEIMMUNE TOLERANCE
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DHBV
IMMUNITY TO DHBVVIRAL INFECTION
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DD1 1 DUCKLINGDUCKLING DHBV ANTIGENSDHBV ANTIGENSDHBV DNADHBV DNA
NO IMMUNITY TO DHBVNO IMMUNITY TO DHBVVIRAL PERSISTENCEVIRAL PERSISTENCE
DHBVDHBV
DHBSAGDHBSAG DHBCAGDHBCAG
STAPHYL. AUSTAPHYL. AUE. COLIE. COLI
ANTIBODYANTIBODYRESPONSERESPONSE
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An immunotolerant duck model for DHBVAn immunotolerant duck model for DHBV
Viral persistence for lifetime
Undetectable both humoral and cellular immune response against DHBV
Active immunization with natural structure of viral protein failed to abrogate immune tolerance
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0 3 6 9 12 15 18 21 24 27 300
25
50
75
100HealthycarrierCHB
month
anti
-HB
s p
osi
tive
rat
e (%
)
Anti-HBs seroconversion after vaccination with conventional protein HBV vaccine
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SOLID MATRIX ANTIBODY SOLID MATRIX ANTIBODY ANTIGEN COMPLEXANTIGEN COMPLEX
(( SMAASMAA ))
DHBsAgDHBsAg
ANTI-ANTI-DHBsDHBs
SPASPA
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Ag: DHBsAgAg: DHBsAg
Ab: Anti-DHsAb: Anti-DHs
One molecule harboring both One molecule harboring both
antigen and antibodyantigen and antibody
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待续 待续
转第二部分转第二部分