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1、疫苗与免疫预防疫苗与免疫预防Vaccine and immunoprophylaxisvWorldwide,vaccine sales are estimated to be approximately US$6.5 billion,representing only two per cent of the global pharmaceutical market,roughly equalling the sales of one successful drug(Greco,2002).v对病原的免疫力分为对病原的免疫力分为先天性先天性和和获得性获得性免疫两种，免疫两种，v免疫预防是疫病控制
2、实践中面临的主要问题，主要免疫预防是疫病控制实践中面临的主要问题，主要通过通过人工被动人工被动及及主动免疫式主动免疫式为动物提供免疫保护。为动物提供免疫保护。v人工主动免疫通过接种疫苗来实现。人工主动免疫通过接种疫苗来实现。v疫苗免疫接种是控制动物疫病的主要手段，疫苗分疫苗免疫接种是控制动物疫病的主要手段，疫苗分活疫苗活疫苗、灭活疫苗灭活疫苗、亚单位疫苗亚单位疫苗及及生物技术疫苗生物技术疫苗几几大类，前两者最为常用，各有优缺点。大类，前两者最为常用，各有优缺点。VACCINOLOGYSUBUNITVACCINEEPITOPEVACCINEVaccines induce protective i
3、mmunity,an enhanced adaptive immune response to re-infection.WHOLEORGANISMPATHOGEN AND HOST如何找到疫苗株如何找到疫苗株/疫苗分子？疫苗分子？传统方法传统方法 找到合适的疫苗株找到合适的疫苗株 找到合适的疫苗分子找到合适的疫苗分子新技术的应用：新技术的应用：v反向疫苗学反向疫苗学v免疫蛋白组学免疫蛋白组学Reverse VaccinologyvThe basic idea behind Reverse Vaccinology is that an entire pathogenic genome can
4、be screened usingbioinformaticsapproaches to find genes.vNext,those genes are filtered for desirable attributes that would make good vaccine targets such as outer membrane proteins.vThose proteins then undergo normal wet lab testing for immune responses.Genome SequenceIn silico analysisHigh throughp
5、utCloning and expression In vitro and in vivo assays forVaccine candidate identificationGlobal genomic approach to identify new vaccine candidatesvAdvantagesFast access to virtually every antigenNon-cultivable can be approachedNon abundant antigens can be identifiedAntigens not expressed in vitro ca
6、n be identified.Non-structural proteins can be usedvDisadvantagesNon proteinous antigens like polysaccharides,glycolipids cannot be used.In Silico AnalysisGene/Protein Sequence DatabaseDisease related protein DBCandidate Epitope DBVACCINOMEPeptideMultitope vaccinesEpitope prediction2D-WB的免疫蛋白组学的免疫蛋白
7、组学IEFSDS-PAGE分析后进行分析后进行质谱鉴定质谱鉴定Western-blot相同的蛋相同的蛋白样品白样品l进行质谱分析进行质谱分析的是染色胶上的的是染色胶上的点点l这些点与转印这些点与转印膜上有免疫反应膜上有免疫反应性的点相对应性的点相对应近年发表的免疫蛋白组学文章vZhang,W.,Liu,G.,Tang,F.,Shao,J.,Lu,Y.,Bao,Y.,Yao,H.,Lu,C.,2011a,Pre-absorbed immunoproteomics:a novel method for the detection of Streptococcus suis surface prot
8、eins.PLoS One 6,e21234.vZhang,W.,Shao,J.,Liu,G.,Tang,F.,Lu,Y.,Zhai,Z.,Wang,Y.,Wu,Z.,Yao,H.,Lu,C.,2011b,Immunoproteomic analysis of bacterial proteins of Actinobacillus pleuropneumoniae serotype 1.Proteome Sci 9,32.vZhang,W.,Lu,C.P.,2007a,Immunoproteomic assay of membrane-associated proteins of Strep
9、tococcus suis type 2 China vaccine strain HA9801.Zoonoses Public Health 54,253-259.vZhang,W.,Lu,C.P.,2007b,Immunoproteomics of extracellular proteins of Chinese virulent strains of Streptococcus suis type 2.Proteomics 7,4468-4476.vWu,Z.,Zhang,W.,Lu,C.,2008b,Immunoproteomic assay of surface proteins
10、of Streptococcus suis serotype 9.FEMS Immunol Med Microbiol 53,52-59.vWu,Z.,Zhang,W.,Lu,Y.,Lu,C.,2010,Transcriptome profiling of zebrafish infected with Streptococcus suis.Microb Pathog 48,178-187.vWu,Z.,Zhang,W.,Shao,J.,Wang,Y.,Lu,Y.,Lu,C.,2011,Immunoproteomic assay of secreted proteins of Streptoc
11、occus suis serotype 9 with convalescent sera from pigs.Folia Microbiol(Praha)56,423-430.vZhu,Y.Z.,Cai,C.S.,Zhang,W.,Guo,H.X.,Zhang,J.P.,Ji,Y.Y.,Ma,G.Y.,Wu,J.L.,Li,Q.T.,Lu,C.P.,Guo,X.K.,2010,Immunoproteomic analysis of human serological antibody responses to vaccination with whole-cell pertussis vacc
12、ine(WCV).PLoS One 5,e13915.第1节 免疫的分类v天然被动免疫天然被动免疫v天然主动免疫天然主动免疫v人工被动免疫人工被动免疫v人工主动免疫人工主动免疫vActive immunity:The production of antibodies against a specific agent by the immune system.Active immunity can be acquired in two ways:vby contracting an infectious disease-such as,for example,chickenpox;or vby
13、receiving a vaccination usually-such as,for example,against polio.vPassive immunity is the transfer of active humoral immunity in the form of readymade antibodies,from one individual to another.vPassive immunity can occur naturally,when maternal antibodies are transferred to the fetus through the pl
14、acenta,vand can also be induced artificially,when high levels of human(or horse)antibodies specific for a pathogen or toxin are transferred to non-immune individuals.v动物在感染某种病原微生物耐过后产生的对该病原动物在感染某种病原微生物耐过后产生的对该病原体再次侵入的抵抗力称为体再次侵入的抵抗力称为天然主动免疫天然主动免疫v动物通过母体胎盘、初乳或卵黄从母体获得某种特动物通过母体胎盘、初乳或卵黄从母体获得某种特异性抗体，从而获得对
15、某种病原体的免疫力，称为异性抗体，从而获得对某种病原体的免疫力，称为天然被动免疫天然被动免疫。v采用人工方法向机体输入由他人或动物产生的免疫采用人工方法向机体输入由他人或动物产生的免疫效应物，如免疫血清、淋巴因子等，使机体立即获效应物，如免疫血清、淋巴因子等，使机体立即获得免疫力得免疫力人工被动免疫人工被动免疫v接种抗原而获得的免疫力接种抗原而获得的免疫力人工主动免疫人工主动免疫 第2节 全微生物疫苗活疫苗（活疫苗（living vaccines）分类分类来源来源弱毒疫苗弱毒疫苗人工致弱人工致弱分离天然弱毒株分离天然弱毒株异源疫苗异源疫苗异源微生物含有共同保护异源微生物含有共同保护性抗原性抗原
16、毒力减弱的方法毒力减弱的方法:v长时间在体外连续培养传代：长时间在体外连续培养传代：v在高于最适生长温度条件下培养在高于最适生长温度条件下培养:炭疽炭疽 v在含有特殊物质的培养基中培养在含有特殊物质的培养基中培养:卡介苗卡介苗 v在特殊气体条件下培养在特殊气体条件下培养:v通过非易感动物通过非易感动物:猪丹毒通过豚鼠猪丹毒通过豚鼠370代后，又通代后，又通过鸡过鸡42代选育而成；猪瘟兔化弱毒代选育而成；猪瘟兔化弱毒 v通过基因工程的方法通过基因工程的方法:去除毒力基因或用点突变，去除毒力基因或用点突变，伪狂犬基因缺失苗伪狂犬基因缺失苗 异源疫苗异源疫苗v是用具有共同保护性抗原的不同病毒制备是用具有共同保护性抗原的不同病毒制备成的疫苗，成的疫苗，v用用火鸡疱疹病毒（火鸡疱疹病毒（HVTHVT）接种预防鸡马立接种预防鸡马立克氏病克氏病v用鸽痘病毒预防鸡痘用鸽痘病毒预防鸡痘v牛痘预防人类天花牛痘预防人类天花Edward JennerDiscovery of small pox vaccineImmunisation against Smallpox WHO Programmev1978:WH
