兔病毒性出血症病毒遗传变异及口服疫苗的研究
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摘要
兔病毒性出血症病毒(rabbit hemorrhagic disease virus,RHDV)属于嵌杯病毒科,基因组为单股正链RNA,基因组长7.5kb。自1984年首次在我国报道兔病毒性出血症(rabbit hemorrhagic disease,RHD)后,该病毒迅速在全球蔓延,给家兔及野生兔带来了巨大威胁。由于缺少有效的病毒培养细胞系,直到今天,RHD的控制仍然使用组织灭活疫苗,但是组织灭活疫苗存在较大的生物安全问题、且不符合动物福利的要求,并且对变异株已不能完全保护。
     2009年秋天到2010年春天陕西数家养兔场暴发疑似RHD的疾病,由于这些养殖场都曾进行RHDV免疫,因此怀疑出现了RHDV变异毒株,导致了RHD在这些养殖场的流行,为揭示造成该现象出现的原因及寻找新的更加有效的防制RHD的方法,本论文进行了系统而深入的研究,具体内容和结果分为以下五个部分:
     1.兔病毒性出血症病毒遗传进化分析
     为研究近期内陕西省境内免疫家兔暴发RHD的原因,分析RHDV国内分离株的遗传变异规律及新的变异情况,从临床发病兔场发病兔肝脏、脾脏等病料,分离病毒,扩增RHDV VP60基因,并进行测序,利用DNAstar及MEGA4软件,对获得的VP60序列及GenBank上传序列的同源性进行分析、比较、并构建系统进化树。结果显示:已报道的16株RHDV VP60序列与2006年~2010年间收集的5株RHDV VP60序列同源性在92%~99.3%间,系统进化分析可将21株国内分离株分成4个群,分别命名为CH1~CH4,CH1仅包含1个分离株——WX/China/1984,该分离株是世界上首例兔病毒性出血症的分离病原,但CH1没有在中国广泛流行,CH2~CH4与CH1在进化树上距离较远,各自成群,代表了不同年代间国内RHDV的流行毒株,CH4是由近几年分离的RHDV构成的一个群,该群内的毒株与CH2及CH3群毒株差异较大,反应了RHDV近几年发生了变异。
     2.兔病毒性出血症病毒的抗原变异分析
     为进一步证实RHDV变异是导致免疫失败的原因,本文选择了与疫苗株NJ/China/1985同属一个群的YL-2006株及不属于同一群的新分离株XA/China/2010毒株对免疫兔进行攻毒试验。共选择24只家兔,其中12只兔30日龄进行免疫,另外12只不进行免疫。在家兔60日龄时分别用YL株和XA/China/2010毒株进行攻毒,每种病毒分别接种免疫家兔和非免疫家兔各6只。结果显示:YL-2006株和XA/China/2010毒株引起非免疫家兔全部死亡,临床症状及病理变化情况相似,以口鼻流血、气管内有粘液,气管及肺脏出血、肝和脾坏死为特征,而免疫组差异较大,免疫组能够完全保护YL-2006株的攻毒,而只为XA/China/2010株提供约50%的免疫保护,说明XA/China/2010抗原表位可能出现了变化,序列比较发现,XA/China/2010与疫苗株存在16个氨基酸的差异,而YL-2006株只有5个氨基酸差异。较多位点的变异可能是导致XA/China/2010攻毒保护效果较差的原因。
     3.减毒沙门氏菌载体的口服兔病毒性出血症疫苗研究
     为研究减毒沙门氏菌作为载体的兔病毒性出血症病毒重组活载体疫苗的免疫效果,构建了表达RHDV主要保护性抗原VP60的真核表达载体pcDNA3-VP60,然后将其电转化到减毒沙门氏菌SL7207菌株中,重组细菌被命名为SL/pcDNA3-VP60;免疫兔子后,检测兔子小肠上皮细胞内VP60基因转录情况,并用ELISA方法、淋巴细胞转化试验及细胞因子测定检测兔子免疫效果,然后用RHDV毒株XA/China/2010进行攻毒。结果显示:减毒沙门氏菌能够有效转导兔腹腔巨噬细胞,重组菌株SL/pcDNA3-VP60能够有效的在兔子体内诱导VP60特异性免疫反应,并且可以为攻毒提供约67%的免疫保护,我们首次证实了重组减毒沙门氏菌作为兔病毒性出血症病毒口服疫苗的可能。
     4.腺病毒基础的兔病毒性出血症口服疫苗的研究
     为进一步改善兔病毒性出血症病毒的口服疫苗的免疫效果,选用复制缺陷性人腺病毒5型腺病毒作为口服疫苗载体,构建了表达VP60的重组腺病毒rAd-VP60,用Westernblot方法检测了目的抗原的表达,然后通过注射、口服和饵料投服的方法免疫了18只兔子,三种免疫方法都成功诱导了RHDV特异的细胞免疫和体液免疫,免疫组的兔子能够完全抵抗RHDV的攻击。腺病毒表达系统成功为兔子提供了免疫保护,尤其饵料免疫方案可以为野兔免疫提供有效的免疫方法。
     5.兔病毒性出血症ELISA检测方法的建立
     为评价兔病毒性出血症疫苗免疫效果,建立了检测兔病毒性出血症病毒抗体间接ELISA方法。对RHDV VP60的主要抗原区域进行表达,经SDS-PAGE和Western blot对表达产物大小及抗原性进行分析,将表达正确、抗原性良好的VP60抗原经纯化后作为ELISA检测抗原,经逐步优化反应条件,建立了兔病毒性出血症病毒ELISA检测方法。VP60抗原基因在大肠杆菌中表达产物大小约为42.34ku,具有良好的反应原性,当以浓度为2.3μg/mL,37℃2h后4℃过夜包被,1%BSA37℃2h封闭,待检血清37℃孵育1h,酶标抗体1:10000稀释,37℃作用1h,底物37℃显色5min的反应条件进行反应时检测效果最好。临界值为0.356;建立的ELISA方法特异性、重复性、敏感性较好;临床检测180份样品,与血凝抑制试验的符合率为74.1%,与商品化试剂盒检测结果符合率为94.8%,该方法可用于临床样品的检测。
     综上所述,本研究系统分析了RHDV自出现以来在我国的流行情况,揭示RHDV新的变异株的出现,证实了传统疫苗对变异株只能诱导部分的保护效率;构建了以减毒沙门氏菌为载体的口服疫苗,并成功诱导了抗原特异性免疫反应,攻毒保护效率达66.7%;进一步选用腺病毒为载体,构建了腺病毒基础的疫苗,构建的重组腺病毒能够表达靶蛋白,通过注射和口服都能够诱导RHDV特异性的免疫反应,并且可以对免疫兔实现100%的免疫保护。该研究为揭示RHDV流行规律及推进RHDV新一代疫苗研究奠定了基础。
RHD virus (RHDV) is a single positive-stranded RNA virus that belongs to theCaliciviridae family with a genome about7.5kb. Since the first report of RHDV in China, thevirus has become a big threaten to both the domestic rabbits and wild rabbits all over of theword. Because the lack of passage cells line for the virus culture, until now, tissue-sourcevaccine is still used to control the disease. However, this vaccine should be avoided in nextgeneration vaccine for bio-security problems and animal welfare.
     From fall of2009till spring of2010, several rabbit keeping farms suffered RHD kinds ofdisease in Shaaxi province. Since these farms have performed a good immunize program forRHDV, some RHDV varieties may involve. To reveal the reason of the stituation and findnew more efficient ways to control RHDV, in current study, a sequence analysis of RHDVbased on VP60were conduced and live recombinant oral vaccines were construced. Thiswork contains5different parts and the details are presented in following paragraphs.
     1. Phylogenetic analysis of RHDV in China
     The study was to investigate rabbit hemorrhagic disease virus (RHDV) in China. VP60sequences of five RHDVs collected by our team, as well as those of16other publishedChinese RHDV strains, were analyzed. Polygenic analysis using MEGA4software showedthat20of the21Chinese strains could be clustered in an RHDVa subgroup, andWX/China/1984was different from them. The Chinese RHDV strains were further classifiedinto4subgroups, CH1to CH4. Subgroup CH1, represented by the WX/China/1984strain,was not prevalent in China after the first RHDV epidemic strain had been reported. The CH2,CH3, and CH4subgroups far different from the CH1subgroup, formed three separate clustersand were distributed according to the time the strains were collected. Recently collectedstrains formed a new subgroup (CH4), represented by new RHDV varieties. The present workis the first comprehensive analysis of Chinese RHDV and reveals a new RHDV variation thatshould be carefully monitored.
     2. New RHDV variations
     RHDV subgroup4(CH4) represent a new variation of RHDV. To analyze the antigen variation of the isolates in this subgroup,3RHDV strains and24rabbits were selected toperform an experiment. YL-2006, XA/China/2010and the vaccine strain NJ/China/1985wereselected. Twelve out of24of the rabbits were immunized by inactived vaccine(NJ/China/1985derived) at30day-old. The other12rabbits were not immunized. At60day-old, these rabbits were challenged using YL-2006and XA/China/2010strain. EachRHDV strain challenged6immunized rabbits and6unimmunized rabbits. The resultsrevealed that all the unimmunized rabbits were dead in36h post challenge. And both virusstrains shared some clinical signs and gross lesions on unimmunized rabbits. But theimmunization provided different level of protection to YL-2006and XA/China/2010. Therabbit challenged with YL-2006were fully protected, but only about50percent of rabbitchallenged with XA/China/2010were protected. This different level of protection may relatedwith amino variation of the challenge strain, as XA/China/2010has16different aminos withvaccine strain and YL-2006has only5amino different in VP60.
     3. S. typhimurium based DNA Vaccine for RHDV control
     The study investigated the utilities of attenuated Salmonella typhimurium as abactofection vehicle for the oral delivery of a DNA vaccine against rabbit hemorrhagicdisease virus (RHDV). The DNA vaccine plasmid pcDNA3-VP60, encoding viral capsidprotein VP60, was transformed into an attenuated S. typhimurium strain SL7207. Theresulting recombinant bacteria, named SL/pcDNA3-VP60, were used to immunize rabbitsorally. Successful delivery of the DNA vaccine plasmid was shown by the detected VP60transcription in intestines through reverse transcriptase-polymerase chain reaction. In addition,RHDV-specific humoral and cell immune response induced by SL/pcDNA3-VP60weredetected by using enzyme-linked immunosorbent assay, T lymphocyte proliferation assay,and cytokine secretion. Experiments with XA/China/2010strains at42dayspost-immunization demonstrated significant protection in immunized rabbits with a relativesurvival rate of66.7%(4/6). The current study demonstrates, for the first time, the ability ofattenuated Salmonella as a live vector to deliver a DNA vaccine orally against RHDV.
     4. Adenovirus-based oral vaccine design
     To futher improve the immune affect of the vaccine, adenovirus was chosen as a vaccinevector and the recombinant adenovirus expressing the RHDV capsid protein (VP60) wasconstructed. The expression of the recombinant protein was identified by western blotanalysis using RHDV-positive rabbit sera. Eighteen rabbits were immunized by injection,direct oral instillation, or using bait. They were challenged with RHDV isolate three weeksafter boost immunization. In all cases, the rabbits immunized with the recombinantadenovirus developed RHDV-specific antibodies and cell immune response. The rabbits injected with the recombinant adenovirus were completely protected against RHDV challenge.The adenovirus expression system may provide a strategy for the immunization of rabbits,particularly for the control of RHDV in wild rabbits.
     5. ELISA for RHDV antibodies detection
     An indirect ELISA method for detecting of antibody against RHDV was established.E.coli expressed VP60was analyzed using SDS-PAGE and Western blot. The identifiedrecombinant protein was used for coating after purification. All the conditions for the ELISAmethod were optimized with standard protocol. The results showed that target fusion proteinwas about42.34ku with a good reactogenicity confirmed by Western blot; the best ELISAreaction condition were found out as: coating with2.9μg/mL of antigen at4℃overnightafter37℃2h; blocking with1%BSA at37℃2h, serum sample reacting (1:100) at37℃for1h, second antibody reacting with HRP labeled goat anti-rabbit (1:10000) at37℃for1hand the threshold of positive and negative sera was0.356. The ELISA method show goodrepeatability, sensitivity and specificity. The coincidence rate was74.1%when comparedwith HI or94.8%when compared with commercial ELIAS kt in detecting180clinical sera.The method can be used for large quantities clinical samples detection.
     In summary, we first comprehensivly ananlyzed the Chinese RHDVs and group theminto four different Chinese subgroups. And based on the rabbit challenge and sequencealignment, a new group of antigenic variation of RHDV was identified. To find out new moreefficient method to replace the tissue-souce RHDV vaccine and control the prevalence ofRHDV, S. typhimurium based DNA Vaccine and adenovirus based live vector vaccine forRHDV were construct and test for RHDV special immune response. We found S.typhimurium based DNA vaccine could induce RHDV special immune response and providepartical protection to RHDV challenge, while adenovirus based vaccine could provide moreeffect protection which may be the useful candidate for RHDV vaccine develop.
引文
白雪东,胡蕴玉,李航,侯黎升,李海峰.小鼠p38MAPK重组腺病毒载体的构建及其在成骨细胞系中的表达[J].细胞与分子免疫学杂志2011,27(4):367-373.
    蔡宝祥.家畜传染病学[M].中国农业出版社,2006.9:376-377.
    陈竞,朱道银,唐恩洁,腺病毒载体的研究进展[J].川北医学院学报,2005,120(4)2:470-472.
    陈伟,杨恒.减毒沙门氏菌作为DNA疫苗载体的研究进展[J].生物技术通报,2010.2(4):38-42.
    董婷,王芳,熊富强,王先炜,范志宇,胡波,王敏敏,李洪广.兔出血症病毒双夹心ELISA检测方法的建立[J].江苏农业学报,2011.27(3):571-576.
    杜念兴,徐为燕,刘胜江,徐福南,虞蕴如,李汝俭.兔出血症研究[J].中国农业科学,1991,24(1):1-10.
    朵红.兔病毒性出血症研究概况[J].青海畜牧兽医杂志,2005,35(3):41-42.
    范凌云,谢庆军,腺病毒载体的研究进展[J].中国生物制品学杂志,2008,2(21)2:153-157.
    范志宇,王岚,王芳,胡波,张则斌,徐为中.醛化人“O”型红细胞的制备及其在兔出血症HA/HI试验中的应用[J].中国养兔.2008,11:20-25.
    巩薇,付瑞,贺争鸣,邢瑞昌.兔出血症病毒RT-PCR方法的研究[J].中国比较医学杂志,2006,16(8):466-468.
    郭建强,姚立红,陈爱珺,刘晓宇,付金奇,徐鹏卫,张智清.共表达H5N1流感病毒M1和HA基因的DNA疫苗与腺病毒载体疫苗的小鼠免疫评价[J].生物工程学报,2011,27(6):876-883.
    贺争鸣,巩薇,梁红,郎淑慧,王秀清,范文平,卫礼,吴惠英.兔出血症病毒(RHDV)McAb的研制及初步应用[J].中国实验动物学杂志,1998,8(4):216-220.
    胡波,魏后军,王芳,范志宇,徐鹏,徐为中,薛家宾,何孔旺.兔出血症病毒RT-PCR检测方法的建立及其临床应用[J].畜牧兽医学报,2010,41(11):1442-1446.
    吉传义,杜念兴,徐为燕,李汝俭.兔出血症病毒细胞培养的初步研究[J].病毒学报,1992,8(3):252-257.
    吉传义,龚晓明,杜念兴.兔出血症病毒细胞培养和组织中的形态发生[J].中国兽医学报,1999,19(5):451-455.
    贾玉,李林芳,钱其军,携带Herceptin-MICB融合蛋白基因的腺病毒载体的构建[J].浙江理工大学学报,2011,28(1)1:111-115.
    蒋文明,姜平,李玉峰,等.串联表达PRRSV M与GPS蛋白重组腺病毒的构建及其免疫特性研究[J].生物工程学报,2006,22(4):555-579.
    李超美,王芳,蔡少平,任雪枫,胡波,范志宇,徐为中,何孔旺.检测兔出血症病毒抗体间接ELISA方法的建立[J].江苏农业学报,2010,26(3):546-550.
    李传山,张婷婷,宋书峰,李维英,孔栋,郭蔼光.串叶松香草高效再生体系的建立与兔出血症病毒YL株外壳蛋白基因VP60对其遗传转化[J].生物技术通报,2007,(5):173-178.
    李嘉,李剑,温婵,羡鲜,张永红,金玉怀,王永祥.CVB3腺病毒载体疫苗Ad/VP1的构建及免疫小鼠的效果[J].基础医学与临床,2011,31(11):1251-1255.
    李卫华,表达HCV-NS3抗原的重组腺病毒载体疫苗的实验研究[D].四川大学,2005.
    李小凤,于花,蓝佳明,张永红,谢立新,刘云宁,尹玉蕾,金玉怀.重组丙型肝炎病毒腺病毒载体疫苗rAd/E2的构建及鉴定[J].中国生物制品学杂志,2011,2,187-191.
    李玉玲,王红宁,曾瑜虹,阳泰,郭自成.携带IBV DNA疫苗重组减毒沙门氏菌的构建及免疫原性研究[J].中国预防兽医学报.2010,32(9):703-707.
    李正,程相朝,减毒沙门氏菌在疫苗和疫苗载体方面的研究进展[J].中国畜牧兽医,2012.39(1):40-44.
    廖成水,程相朝.减毒沙门氏菌作为抗肿瘤及肿瘤基因治疗载体的研究进展[J].生物学通报,2010,45(11):1-4.
    刘根梅,陈瑞爱,罗满林.腺病毒载体的研究进展[J].广东农业科学,2010(4):188-190.
    刘光清,张玉颖,云涛,倪征,张淼涛,梁华丽,华炯刚,李双茂,杜青云,盛祖恬.兔病毒性出血症病毒基因组3′端非编码区的分子克隆及生物信息学分析[J].西北农林科技大学学报(自然科学版),2006,34(3):16-20.
    刘怀然,胡迎东,陈洪岩,张玲,李昌文,关云涛,曲连东.兔出血症病毒VP60蛋白的原核表达及检测方法初步应用[J].中国预防兽医学报,2006,28(2):201-204.
    刘怀然,刘家森,胡迎东,陈洪岩,单安山,曲连东.兔出血症病毒VP60基因在昆虫细胞中形成病毒样颗粒及其特性[J].中国比较医学杂志.2007,8:448-454.
    刘怀然,曲连东,刘家森,单安山.昆虫细胞表达兔出血症VP60蛋白间接ELISA方法建立及评价[J].东北农业大学学报,2010,41(8):81-88.
    刘胜江,薛华平,浦伯清,钱年华,徐为燕,杜念兴.兔的一种新病毒病—兔病毒性出血症[J].畜牧与兽医,1984,16(6):253-255.
    刘馨,张光明,李鸿钊,谢天宏,孙茂盛.表达轮状病毒VP4抗原的重组腺病毒对新生小鼠的被动免疫保护作用[J].中国生物制品杂志,2007,20(1):33-36.
    卢觅佳,周国亮,李峰,王湛,周玲,陈云祥,由振强,温磊,宣尧仙.腺病毒载体疫苗在恒河猴体内的长期毒性试验[J].中国药理学通报,2007,23(7):953-958.
    陆承平.兽医微生物学(第四版)[M].北京:中国农业出版社,2007.8:457
    秦海斌,刘怀然,刘家森,姜骞,韩凌霞,司昌德,曲连东.兔出血症病毒抗原捕获ELISA检测方法[J]中国比较医学杂志,2007,8:20-24.
    秦海斌,刘怀然,曲连东,刘家森,韩凌霞,姜骞,李亚明,杨增岐.兔出血症病毒抗原捕获ELISA检测方法的建立.中国兽医学报,2008.28(1):28-31.
    秦海斌.兔出血症病毒单克隆抗体的制备及抗原捕获ELISA检测方法的建立[硕士学位论文].西北农林科技大学.2007.
    邱峰,陈世知,陈虹.新型腺病毒载体的制备及其特性研究[J].重庆医科大学学报,2006,31(3):330-333.
    施明,王福生,高兰兴,腺病毒载体的研究进展[J].世界华人消化杂志,2000,8(11):1282-1286.
    宋英今,郎守民,李在成.金银染色三抗体夹心法检测兔出血症病毒(RHDV)抗原[J]延边大学农学学报,2001,23(2):88-92.
    孙诚谊,胡朝全,孙连生,王玉芝,王百林.重组腺病毒载体介导人OSM基因对胰腺癌细胞增殖的抑制作用及对裸鼠致瘤性的影响[J].中华肝胆外科杂志,2004,10(4):267-269.
    汤景元,姜平,蒋文明,马苏,李玉峰.表达PRRSV M蛋白重组腺病毒的构建及其免疫特性研究[J].中国病毒学,2005,20(6):618-622.
    田浪,王红宁,李建文,廖娟,张夏兰,周万蓉,王鸿宾.一株无血凝性兔出血症病毒的分离鉴定及其衣壳蛋白VP60基因的克隆和序列分析[J].畜牧兽医学报,2006,37(10),1078-1083.
    王德利,腺病毒载体的研究进展[J].海军总医院学报,2004,17(4):227-230.
    王芳,李超美,杨龙圣,徐为中,张则斌,侯玉峰,陈国强,何孔旺.兔出血症病毒RT-PCR检测方法的建立及应用[J].农业生物技术学报.2007,15(3):409-413.
    王克领,郎利敏,郭秀琦,王四保,魏成斌.兔出血症病毒对人类红细胞的血凝谱研究[J].中国养兔杂志,1999,6:17-19.
    王龙涛,葛晨霞,马磊,李海峰,张守发.2010.兔病毒性出血症Dot-IGSS检测方法的建立,安徽农业科学,38(31):17718-17719.
    王涛,ats1A启动子驱动的兔出血症病毒外壳蛋白VP60基因的植物表达载体构建及百脉根的转化[D].西北农林科技大学,2009.
    王先炜.猪圆环病毒2型人工感染和重组腺病毒基因工程疫苗研究[D].南京农业大学,2006.
    王永山,陆承平,周宗安,陈兴祥.基因重组抗原酶联免疫法检测兔出血症病毒抗体及其标准化[J].中国兽医学报,2004,24(03):233-235.
    王云峰,陈洪岩,夏长友,尹延宏,张靖飞,刘怀然.对兔病毒性出血症疫苗及其使用方法的几点看法[J].中国养兔杂志,2002,2:14-15.
    武昱孜,贾广乐,张映,张旭.兔出血症病毒检测方法研究进展.中国畜牧兽医,2010.37(10):170-173.
    严维巍,崔治中,王永坤.兔出血症病毒衣壳蛋白基因在毕赤酵母中的表达[J].生物工程学报,2005,21(1):135-138.
    严维巍,崔治中,王永坤.在昆虫细胞中表达能自聚成病毒样颗粒的兔出血症病毒衣壳蛋白[J].病毒学报,2004,20(4):333-337.
    杨汉春,徐为燕,杜念兴.兔出血症病毒血凝特性的研究[J].畜牧兽医学报,1988,S(1):138-143.
    张福良,王双山,欧阳素贞.猪圆环病毒2型Rep、Cap蛋白基因串联重组腺病毒的构建及其免疫效果研究[J].中国预防兽医学报,2008,30(10):775-778.
    张蕾,以减毒沙门菌为载体的H5亚型禽流感和SARS口服疫苗的研究[D].吉林大学,2008.
    张夏兰,王红宁,张昌菊,向菁,徐永莉,余协中,兔病毒性出血症基因工程疫苗的研究进展[J].中国预防兽医学报.2007,29(10):821-824.
    张玉颖,刘光清,吴润.兔出血症病毒分子生物学研究进展[J].动物医学进展,2006,27(3):9-13.
    赵丽晶,以减毒沙门氏菌携带HPV16L1和siRNA-E6共表达质粒防治子宫颈癌的研究[博士学位论文].吉林大学2010.
    郑东,T.Xue,堪东华,郑明,Z.H Zhou,徐伟.利用低温电镜术和像重构方法研究兔出血症病毒的三维结构[J].科学通报,2001.46(1):39-43.
    郑东,谌东华,TaoXUE,郑明,Z H Zhou,徐伟.低温电镜术证实了兔出血症病毒亚基因组颗粒的存在[J].电子显微学报,2000,19(05):661-666.
    周文伟,刘月环,实验兔出血症病毒检测方法的建立与免疫效果调查[J].中国比较医学杂志,2010,20(4):59-62.
    周玉龙,任亚超,朱战波,侯喜林,王密,耿晶,朴范泽,李森.牛副粘病毒3型HN基因原核表达及间接ELISA方法建立[J].病毒学报,2012.28(1):23-26.
    周智君,陈军,俞远京,肖献忠.兔出血症病毒套式PCR检测方法的建立[J].湖南农业大学学报(自然科学版),2006,32(3):261-263.
    庄国宏,朱国强,周继宏,卞为民,陈宝林,王永坤.兔瘟油乳剂灭活疫苗免疫效果初探[J].中国养兔杂志,1995,2:23-25.
    Abu Elzein,E.M.E.,Al-Afaleq,A.L.,Rabbit haemorrhagic disease in Saudi Arabia[J]. VeterinaryRecord.1999,144:480-481.
    Ahmad K.Adenovirus vaccine works best [J].The Lancet Oncology,2003,4(10):558.
    Asgari S.,Hardy J.R.E.,Sinclair R.G.,Cooke B.D.,Field evidence for mechanical transmission of rabbithaemorrhagic disease virus (RHDV) by flies (Diptera: Calliphoridae) among wild rabbits inAustralia[J]. Virus research,1998,54(2),123-132.
    Asgari,S.,Hardy,J.R.E.,Cooke,B.D.,Sequence analysis of rabbit haemorrhagic disease virus (RHDV) inAustralia: alterations after its release[J].Archives of Virology.1999,144,135-145.
    Ashby D.,Leduc I.,Lauzon W.,Craig Lee B.,Singhal N.,Cameron D.W.,Attenuated Salmonella typhimurium SL3261as a vaccine vector for recombinant antigen in rabbits[J].Journal of ImmunologicalMethods,2005,.299(1-2),153-164.
    Ashraf,S., Kong,W.,Wang,S.,Yang, J., Curtiss Iii, R.,2011, Protective cellular responses elicited byvaccination with influenza nucleoprotein delivered by a live recombinant attenuated Salmonellavaccine.Vaccine29,3990-4002.
    Avogadri F,Martinoli C,Petrovska L,Chiodoni C,Transidico P,Bronte V,Longhi R,Colombo MP,DouganG,Rescigno M.Cancer immunotherapy based on killing of Salmonella-infected tumor cells.CancerRes.2005,65(9):3920-7.
    Barcena J,Morales M,Vazquez B,Boga JA,Parra F,Lucientes J,Pages Mante A, SanchezVizcaino J M,Blasco R,Torres J M. Horizontal Transmissible Protection against Myxomatosis and Rabbit HemorrhcDisease by Using a Recombinant myxoma virus.J Virol.2000,74(3):1114-23.
    Baud D,Ponci F,Bobst M,Grandi PD,Denise Nardelli-Haefliger.Improved efficiency of a Salmonella-basedvaccine against human papillomavirus type16virus-like particles achieved by using acodon-optimized version of L1[J].Journal of Virology,2004,78(23):12901-12909.
    Bauer H,Darji A,Chakraborty T,Weiss S.Salmonella-mediated oral DNA vaccination using stabilizedeukaryotic expression plasmids[J].Gene Therapy,2005,12(4):364-372.
    Bengt Johansson-Lindbom,Marcus Svensson,Marc-André Wurbel,Bernard Malissen,Gabriel Márquez andWilliam Agace.Selective generation of gut tropic T cells in gut-associated lymphoid tissue(GALT)[J].The Journal of experimental medicine.2003,198(6):963-969.
    Bertagnoli S,Gelfi J,Petit F,Vautherot J F,Rasschaert D,Laurent S,Gall G L,Boilletot E,ChantalJ,Boucraut-Baralon C.Protection of rabbits against rabbit viral haemorrhagic disease with avaccinia-RHDV recombinant virus [J]. Vaccine,1996,14(6):506-510.
    Bertagnoli S.,Gelfi J.,Le Gall G.,Boilletot E.,Vautherot J.F.,Rasschaert D.,Laurent S., Petit F.,Boucraut-Baralon C.,Milon A., Protection against myxomatosis and rabbit viral hemorrhagic diseasewith recombinant myxoma viruses expressing rabbit hemorrhagic disease virus capsid protein[J].Journal of Virology.1996,70(8),5061-5066.
    Biermann U,Herbst W,Baljer G.Rabbit hemorrhagic disease(RHD)--comparative diagnostic studies usingthe hemagglutination test and electron microscopy[J].Berl Munch TierarztlWochenschr,1992,105(3):86-87.
    Boga J A,Mart J M,Casais R,Parra F.A single dose immunization with rabbit haemorrhagic disease virusmajor capsid protein produced in Saccharomyces cerevisiae induces protection [J].Journal of GeneralVirology,1997,78(9):2315-2318.
    Boga JA, Casais R, Marin MS, Martin-Alonso JM,Carmenes RS,Prieto M,Parra F. Molecularcloning,squencing and expression in Escherichia coli of the capsid protein gene from rabbithaemorrhagic disease virus (Spanish isolate AST/89)[J]. The Journal of GeneralVirology,1994,75(9):2409-2413.
    Brandtzaeg P,Prydz H.Direct evidence for an integrated function of J chain and secretory component inepithelial transport of immunoglobulins[J]. Nature.1984,311(5981):71-73.
    Campbell JJ,Brightling CE,Symon FA,Qin S,Murphy KE, Hodge M,Andrew DP,Wu L, ButcherEC,Wardlaw AJ.Expression of chemokine receptors by lung T cells from normal and asthmaticsubjects[J].The Journal of Immunology.2001,166(4):2842-2848.
    Cancellotti FM,Renzi M.Epidemiology and current situation of viral haemorrhagic disease of rabbits andthe European brown hare syndrome in Italy[J].Rev Sci Tech.1991,10(2):409-422.
    Capucci L,Scicluna MT,Lavazza A.Diagnosis of viral haemorrhagic disease of rabbits and the Europeanbrown hare syndrome[J].Rev Sci Tech.1991,10(2):347-370.
    Capucci L.,Fallacara F.,Grazioli S.,Lavazza A.,Pacciarini M.L.,Brocchi E.,A further step in the evolution ofrabbit hemorrhagic disease virus: the appearance of the first consistent antigenic variant[J].VirusResearch,1998,58(1-2),115-126.
    Castanon S,Marin M S,Martin-Alonso J M, Boga J A,Casais R,Humara J M,Ordas R J,ParraF.Immunization with Potato Plants Expressing VP60Protein Protects against Rabbit HemorrhagicDisease Virus[J].Journal of Virology,1999,73(5):4452-4455.
    Castanon S.,Martin-Alonso J M.,Maria M.S.,Boga J.A.,Alonso P.,Parra F.,Ordas R J.The effect of thepromoter on expression of VP60gene from rabbit hemorrhagic disease virus in potato plants[J].PlantScience,2002,162(1):87-95.
    Charlton K.M.,Artois M., Prevec L.,Campbell J.B.,Casey G.A.,Wandeler A.I., Armstrong J.,Oral rabiesvaccination of skunks and foxes with a recombinant human adenovirus vaccine[J].Archives ofvirology,1992,123(1-2),169-179.
    Chen H.,Schifferli D.M.,Mucosal and systemic immune responses to chimeric fimbriae expressedbySalmonella enterica serovar Typhimurium vaccine strains[J].Infection and Immunity,2000,68(6),3129-3139.
    Clarke I.N.,Lambden P.R.The molecular biology of caliciviruses[J].Jourmal of General Virology,1997,78:291-301.
    Cochlovius B,Stassar MJ,Schreurs MW,Benner A,Adema GJ.Oral DNA vaccination: antigen uptake andpresentation by dendritic cells elicits protective immunity[J].Immunology Letters,2002,80(2):89-96.
    Collins B J,White J R,Lenghaus C,Boyd V,Westbury H A.A competition ELISA for the detection ofantibodies to rabbit haemorrhagic disease virus[J].Veterinary Microbiology,1995,43(1):85-96.
    Cooke B.D., McPhee S.,Robinson A.J.,Capucci L.,Rabbit haemorrhagic disease:doe-sa preexistingRHDV-like virus reduce the effectiveness of RHD asa biological control in Australia[J].WildlifeResearch,2002,29(5),673-682.
    Cooke,B.D.,Rabbit haemorrhagic disease:field epidemiology and the management of wild rabbitpopulations[J].Revue scientifique&technique-Office international des épizooties,2002,21(2),347-358.
    Cuburu N,Kweon MN,Song JH,Hervouet C,Luci C,Sun JB,Hofman P,Holmgren J,Anjuère F,CzerkinskyC.Sublingual immunization induces broad-based systemic and mucosal immune responses inmice[J].Vaccine2007,25(51):8598-8610.
    Czerkinsky C,Anjueie F,McGhee JR,Geoige-Chandy A,Holmgren J,Kieny MP, Fujiyashi K,MesteckyJF,Pierrefite-Carle V,Rusk C,Sun JB.Mucosal immunity and tolerance: relevance to vaccinedevelopment[J]. Immunological reviews.1999,170(1):197-222.
    Darji A,Guzman CA,Gerstel B,Wachholz P,Timmis KN,Wehland J,Chakraborty T,Weiss S.Oral somatictransgene vaccination using attenuated S.Typhimurium[J].Cell,1997,91(6):765-775.
    David Chasey.Rabbit haemorrhagic disease:the new scourge of Oryctolagus cuniculus[J].LabororyAnimals1997.31(1):33-44.
    Dunham D.M.,Jiang X.,Berke T.,Smith A.W.,Matson D.O..Genomic mapping of a calicivirusVPg[J].Archives of Virology,1998,143(12):2421-2430.
    Farnós O,Boué O,Parra F,Martín-Alonso JM,Valdés O,Joglar M,Navea L,Naranjo P, Lleonart R.High-levelexpression and immunogenic properties of the recombinant rabbit hemorrhagic disease virus VP60capsid protein obtained in Pichia pastoris[J].Journal of Biotechnology,2005,117(3):215-224.
    Farnos O,Rodriguez M,Chiong M,Parra F,Boue O,Lorenzo N,Colas M,Lleonart R. The recombinant rabbithemorrhagic disease virus VP60protein obtained from Pichia pastoris induces a strong humoral andcell-mediated immune response following intranasal immunization in mice [J].VeterinaryMicrobiology,2006,114(3-4):187-195.
    Farnos O.,Rodriguez D.,Valdes O.,Chiong M.,Parra F.,Toledo J.R.,Fernandez E.,Lleonart R., Suarez M.,Molecular and antigenic characterization of rabbit hemorrhagic disease virus isolated in Cuba indicatesa distinct antigenic subtype[J].Archives of Virology.2007,152(6),1215-1221.
    Ferguson A.,Humphreys K.A.,Croft N.M.,Technical report:results of immunological tests on faecal extractsare likely to be extremely misleading[J]. Clinical﹠Experimental Immunology,1995,99(1),70-75.
    Fischer L,Le Gros F X,Mason P W,Paoletti E.A recombinant canarypox virus protects rabbits againstalethal rabbit hemorrhagic disease virus (RHDV) challenge[J].Vaccine.1997.15(1):90-96.
    Forrester N.L.,Abubakr M.I.,Abu Elzein E.M.E.,Al-Afaleq A.I.,Housawi F.M.T., Moss S.R.,TurnerS.L.,Gould, E.A.,Phylogenetic analysis of Rabbit haemorrhagic disease virus strains from the ArabianPeninsula:Did RHDV emerge simultaneously in Europe and Asia[J].Virology,2006,344(2),277-282.
    Gelmetti D,Grieco V,Rossi C,Capucci L,Lavazza A.Detection of rabbit haemorrhagic disease virus (RHDV)by in situ hybridisation with a digoxigenin labelled RNA probe [J].Journal of VirologicalMethods,1998,72(2):219-226.
    Gentschev I,Dietrich G,Spreng S,Neuhaus B,Maier E,Benz R,Goebel W,Fensterle J,Rapp UR.Use of thehemolysin secretion system of Escherichia coli for antigen delivery in the Salmonella typhi Ty21avaccine strain[J].International Journal of Medical Microbiology.2004,294(6):363-371.
    Glenn GM,Rao M,Matyas GR,Alving CR.Skin immunization made possible by choleratoxin[J].Nature.1998;391(6670):851-852.
    Gould A.R.,Kattenbelt J.A.,Lenghaus C.,Morrissy C.,Chamberlain T.,Collins B.J.,Westbury H.A..Thecomplete nucleotide sequence of rabbit haemorrhagic disease virus(Czech strain V351):use of thepolymerase chain reaction to detect replication in Australian vertebrates and analysis of viralpopulation sequence variation[J].Virus Research,1997,47(1):7-17.
    Grazioli, S.,Agnoletti,F.,Scicluna, M.,Masoero, N.,Guercio, A.,Fallacara, F., Lavazza, A.,Brocchi,E.,Capucci, L.,2000.Rabbit haemorrhagic disease virus (RHDV) subtype''A"(RHDVa) is replacing theoriginal strain in some Italian regions.In: Fifth International Congress of the European Society forVeterinary Virology, Brescia,Italy, pp.27-30.
    Gregg DA,House C,Meyer R,Berninger M.Viral haemorrhagic disease of rabbits in Mexico:epidemiologyand viral characterization[J].Rev Sci Tech.1991,10(2):435-451.
    Gregor Meyers,Christoph Wirblich,Heinz-Jürgen Thiel,J rg Oliver Thumfart.Rabbit hemorrhagic diseasevirus:genome organization and polyprotein processing of a calicivirus studied after transientexpression of cDNA constructs[J]. Virology,2000,276(2):349-363.
    Guittre C,Baginski,Gall G L,Prave M,Trepo C,Cova L.Detection of rabbit haemorrhagic disease virusisolates and sequence comparison of the N-terminus of the capsid protein gene by the polymerasechain reaction[J].Research in Veterinary Science,1995,58(2):128-132.
    Habing G.G.,Neuder L.M.,Raphael W.,Piper-Youngs H.,Kaneene J.B.,Efficacy of oral admin-istration of amodified-live Salmonella Dublin vaccine in calves[J]. Journal of the American Veterinary MedicalAssociation,2011,238(9),1184-1190.
    Haroldo Toro,De-chu C.Tang,David L.Suarez,Matt J.Sylte,Jennifer Pfeiffer,Kent R. Van Kampen.Protectiveavian influenza in ovo vaccination with non-replicating human adenovirusvector[J].Vaccine,2007,25(15):2886-2891.
    Harrison J.A.,Villarreal-Ramos B.,Mastroeni P.,Demarco de Hormaeche R., Hormaeche C.E., Correlates ofprotection induced by live Aro_Salmonella typhimurium vaccines in the murine typhoid model[J].Immunology,1997,90(4),618-625.
    Henderson H.,Jackson F.,Bean K.,Panasuk B.,Niezgoda M.,Slate D.,Li J., Dietzschold B.,MattisJ.,Rupprecht C.E.,Oral immunization of raccoons and skunks with a canine adenovirus recombinantrabies vaccine[J].Vaccine,2009,27(51),7194-7197.
    Holden C.Rabbit Biocontrol Project in Disarray[J].Science,1995;270:1123.
    Holmgren J,Czerkinsky C.Mucosal immunity and vaccines[J].Nature medicine.2005;11:S45-S53.
    Hopkins SA,Niedergang F,Corthesy-Theulaz IE,Kraehenbuhl.A recombinant Salmonella typhimuriumvaccine strain is taken up and survives within murine Peyer’s Patch dendritic cells[J].CellularMicrobiology.2000,2(1):59-68.
    Hu Z.,Tian X.,Zhai Y.,Xu W.,Zheng D.,Sun F.,Cryo-Electron Microscopy Reconstructions of Two Types ofWild Rabbit Hemorrhagic Disease Viruses Characterized the Structural Features of Lagovirus[J].Protein Cell,2010,1(1):48-58.
    Iwasaki A. ucosal dendritic cells[J].Annual Review of Immunology.2007,25:381-418.
    Iwata M,Hirakiyama A,Eshima Y,Kagechika H,Kato C,Song SY.Retinoic acid imprints gut-homingspecificity on T cells. Immunity.2004,21(4):527-538.
    J Rohde,H Schirrmeier,H Granzow,HJ Rziha..A new recombinant Orf virus (ORFV, Parapoxvirus) protectsrabbits against lethal infection with rabbit hemorrhagic disease virus (RHDV). Vaccine,2011,29(49):9256-9264.
    Jang MH,Kweon MN,Iwatani K,Yamamoto M,Terahara K,Sasakawa C,Suzuki T,Nochi T, YokotaY,Rennert PD,Hiroi T,Tamagawa H,Iijima H,Kunisawa J,Yuki Y,Kiyono H. Intestinal villous Mcells:an antigen entry site in the mucosal epithelium[J]. Proceedings of the National Academy ofSciences of the United States of America.2004,101(16):6110-6115.
    Jiang P.,Jiang W.,Li Y.,Wu S.,Xu J.,Humoral immune response induced by oral administra-tion of S.typhimurium containing a DNA vaccine against porcine reproductive and respiratory syndromevirus[J]. Veterinary Immunology and Immunopathology,2004,102(3),321-328.
    Joana Abrantes,Wessel van der Loo,Jacques Le Pendu,Pedro J Esteves.Rabbit haemorrhagic disease (RHD)and rabbit hemorrhagic disease virus (RHDV):a review[J]Veterinary Research2012,43:12.
    Johansson EL,Wassén L,Holmgren J,Jertborn M,Rudin A.Nasal and vaginal vaccinations have differentialeffects on antibody responses in vaginal and cervical secretions in humans[J].Infection and immunity.2001,69(12):7481-7486.
    Jones BD,Ghori N,Falkow S.Salmonella typhimurium initiates murine infection by Penetrating anddestroying the specialized epithelial M cells of the Peyer’s Patches[J].The Journal of ExperimentalMedicine,1994,180(1):15-23.
    Joubert P,Pautigny C,Madelaine MF,Rasschaert D.Identification of a new cleavage site of the3C-likeprotease of rabbit haemorrhagic disease virus[J].Journal of General Virology,2000,81(2):481-488.
    Juan Bárcena,Nuria Verdaguer,Ramón Roca,Mónica Morales,Iván Angulo,Cristina Risco,JoséL.Carrascosa,Juan M.Torres,José R.Castón.The coat protein of rabbit hemorrhagic disease viruscontains a molecular switch at the N-terminal region facing the inner surface of the capsid[J]. Virology,2004,322(1):118-134.
    Juan Bárcena,Mónica Morales,Belén Vázquez,José A.Boga,Francisco Parra,Javier Lucientes,AlbertPagès-Manté,José M.Sánchez-Vizcaíno,Rafael Blasco,Juan M. Torres Horizontal transmissibleprotection against myxomatosis and rabbit hemorrhagic disease by using a recombinant myxomavirus[J].Journal of Virology,2000,74(3):1114-1123.
    Kaetzel CS.The polymeric immunoglobulin receptor:bridging innate and adaptive immune responses atmucosal surfaces[J].Immunological reviews.2005,206(1):83-99.
    Kaiser J.Aussie rabbit virus causes ruckus[J].Seience,1995,270:583.
    Kerr P.J.,Kitchen A.,Holmes E.C.,Origin and phylodynamics of rabbit hemorrhagic disease virus[J].Journalof Virology,2009,83(23),12129-12138.
    Kiyono H,Fukuyama S.NALT-versus Peyer's-patch-mediated mucosal immunity[J]. Nature ReviewsImmunology.2004,4(9):699-710.
    Koichi Takayama,Akiko Ikegami,Hiroyuki Inoue,Lioudmila Kaliberova,Junji Uchino, DavidT.Curiel,Yoichi Nakanishi.VEGF promoterbased conditionally replicative adenoviruses are usefulfor the treatment of malignant pleural mesothelioma [J]. Molecular Therapy.20049(S1):S238.
    Konig M,Thiel H J,Meyers G.Detection of Viral Proteins after Infection of Cultured Hepatocytes withRabbit hemorrhagic Disease virus[J].Journal of Virology,1998,72(5):4492-4497.
    Kotton C.N.,Hohmann E.L.,Enteric pathogens as vaccine vectors for foreign antigen delivery[J].InfectionImmunity,2004,72(10),5535-5547.
    Kunisawa J, Kiyono H. A marvel of mucosal T cells and secretory antibodies for the creation of first linesof defense[J].Cellular and molecular life sciences2005,62(12):1308-1321.
    Laurent S,Kut E,Remy-Delaunay S,Rasschaert D.Folding of the rabbit hemorrhagic disease virus capsidprotein and delineation of N-terminal domains dispensable for assembly[J]. Archives of Virology.2002,147(8):1559-1571.
    Laurent S,Vautherot J F,Madelaine M F,Gall G L,Rasschaert D.Recombinant rabbit hemorrhagic diseasevirus capsid protein expressed in baculovirus self-assembles into viruslike particles and inducesprotection[J].Journal of Virology,1994,68(10):6794-6798.
    Le Gall G.,Arnauld C.,Boilletot E.,Morisse JP,Rasschaert D.,Molecular epidemiology of rabbithaemorrhagic disease virus outbreaks in France during1988to1995[J].Journal of General Virology,1998,79(1),11-16.
    Le Gall-Reculé G.,Zwingelstein F.,Laurent S.,De Boisseson C.,Portejoie Y.,Rasschaert D.,Phylogeneticanalysis of rabbit haemorrhagic disease virus in France between1993and2000and thecharacterisation of RHDV antigenic variants. Arch virol,2003,148(1),65-81.
    Li L,Fang W,Li J,Fang L,Huang Y,Yu L.Oral DNA vaccination with the polyprotein gene of infectiousbursal disease virus (IBDV)delivered by attenuated Salmonella elicits protective immune responses inchickens[J].Vaccine,2006,24(33-34):5919-5927.
    Liu, S.,Xue, H.,Pu, B.,Qian, N., A new viral disease in rabbits. Anim Husb Vet Med1984,16,253-255.
    Lo W.F.,Ong H.,Metcalf E.S.,Soloski M.J.,T cell responses to Gramnegative Intracellularbacterialpathogens: a role for CD8+T cells in immunity to Salmonella infection and the involvementof MHC class Ib molecules[J].J.Immunol.1999,162(9),5398-5406.
    Loessner H, Weiss S. Bacteria-mediated DNA transfer in gene therapy and vaccination[J]. Expert Opinionon Biological Therapy,2004,4(2):157-168.
    M Quiding,I Nordstr m,A Kilander,G Andersson,L A Hanson, J Holmgren, and C Czerkinsky. Intestinalimmune responses in humans. Oral cholera vaccination induces strong intestinal antibody responsesand interferon-gamma production and evokes local immunological memory[J].The Journal of ClinicalInvestigation.1991,88(1):143-148.
    Ma W.,Yu L.,Analysis of two VP60capsid protein genes of rabbit hemorrhagic disease virus from virusesobtained from the same farm[J]. Archives Virology,2010,155(9),1497-1501.
    Machin A.,Martin Alonso J.M.,Dalton K.P.,Parra F.,Functional differences between precursor and matureforms of the RNA-dependent RNA polymerase from rabbit hemorrhagic disease virus[J]. Journal ofGeneral Virology,2009,90(9),2114-2118.
    Marin M S,Alonso J M M,Garcia LIPO,Boga J A,Arguello-Villares J,Casais R,Venugopal K,Jiang W,GouldE A,Parra F.Immunogenic properties of rabbit haemorrhagic disease virus structural protein VP60expressed by a recombinant baculovirus: an efficient vaccine[J],Virus Research,1995,39(2-3):119-128.
    Martin Alonso JM,Casais R,Boga JA,Parra F.Processing of rabbit hemorrhagic disease viruspolyprotein[J].Journal of Virology,1996,70(2):1261-1265.
    Martínez-Torrecuadrada JL,Cortés E,Vela C,Langeveld JP,Meloen RH,Dalsgaard K, Hamilton WD, CasalJI.Antigenic structure of the capsid protein of rabbit haemorrhagic disease virus[J].Journal of GeneralVirology,1998,79(8):1901-1909.
    Matiz K.,Ursu K., Kecskemeti S.,Bajmocy E., Kiss I.,Phylogenetic analysis of rabbit haemorrhagic diseasevirus (RHDV) strains isolated between1988and2003in eastern Hungary[J].Archives ofVirology,2006,151(8),1659-1666.
    McGhee JR,Fujihashi K,Beagley KW,Kiyono H.Role of interleukin-6in human and mouse mucosal IgAplasma cell responses[J].Immunologic research.1991,10(3-4):418-422.
    Mcintosh M.T.,Behan S.C.,Mohamed F.M.,Lu Z.,Moran K.E.,Burrage T.G.,Neilan J.G.,Ward G.B.,BottiG.,Capucci L.,A pandemic strain of calicivirus threatens rabbit industries in the Americas[J]VirologyJournal,2007,4(96):1-13.
    Mestecky J,Russell MW,Elson CO.Perspectives on mucosal vaccines:Is mucosal tolerance a barrier[J].TheJournal of Immunology2007,179(9):5633-5638.
    Meyers G,Wirblich C,Thiel H J.Rabbit hemorrhagic disease virus-molecular cloning and nucleotidesequencing of a calicivirus genome[J].Virology,1991,184(2):664-676.
    Meyers G.,Wirblich C.,Thiel H.J.,Genomic and subgenomic RNAs of rabbit hemorrhagic disease virus areboth protein-linked and packaged into particles[J].Virology,1991,184(2),677-686.
    Meyers G.Translation of the minor capsid protein of a calicivirus is initiated by a novel termination-dependent reinitiation mechanism[J].The Journal of Biological Chemistry,2003,278:34051-34060.
    Mikami O.,Park J.H,Kimura T.,Ochiai K.,Itakura C.,Hepatic lesions in young rabbits experimentallyinfected with rabbit haemorrhagic disease virus[J].Research in VeterinaryScience,1999,66(3),237-242.
    Milton,I.D.,Vlasak R.,Nowotny N.,Rodak L.,Carter M.J.,Genomic3'terminal sequence comparison of threeisolates of rabbit haemorrhagic disease virus[J].FEMS Microbiology Letters,1992,93(1),37-42.
    Mora JR,Bono MR,Manjunath N,Weninger W,Cavanagh LL,Rosemblatt M,Von Andrian UH. Selectiveimprinting of gut-homing T cells by Peyer's patch dendritic cells[J]. Nature.2003,424(6944):88-93.
    Mora JR,Iwata M,Eksteen B,Song SY,Junt T,Senman B,Otipoby KL,Yokota A,Takeuchi H,Ricciardi-Castagnoli P,Rajewsky K, Adams DH, von Andrian UH.Generation of gut-homingIgAsecreting B cells by intestinal dendritic cells[J].Science.2006,314(5802):1157-1160.
    Morales M,Barcena J,Ramirez M A,Jose A,Boga,Parra F,Torres J M.Synthesis in Vitro of RabbitHemorrhagic Disease Virus Subgenomic RNA by Internal Initiation on (-) Sense GenomicRNA:Mapping of a subgenomic promoter[J].The Journal of BiologicalChemistry,2004,279(17):17013-17018.
    Morisse J P,Le Gall G,Boilletot E.HePatitis of viral origin in LePoridae:introduetion and aetiologiealhyPotheses.Revue Scientifique et Teehnique de office Lnternational des Epizooties1991,(10):283-95.
    Muller A.,Freitas J.,Silva E.,Le Gall-Reculé G.,Zwingelstein F.,AbrantesJ.,Esteves P.J., Alves P.C., VanDer Loo W., Kolodziejek J.,Nowotny N.,Thompson G., Evolution of rabbit haemorrhagic diseasevirus (RHDV) in the European rabbit (Oryctolagus cuniculus) from the Iberian Peninsula[J].Veterinary Microbiology,2009,135(3-4),368-373.
    Muramatsu M,Kinoshita K,Fagarasan S,Yamada S,Shinkai Y,Honjo T.Class switch recombination andhypermutation require activation-induced cytidine deaminase (AID),a potential RNA editingenzyme[J].Cell.2000,102(5):553-563.
    Nadeau I,Kamen A.Production of adenovirus vector for gene therapy[J].Biotechnology Advances,2003,20(7-8):475-489.
    Neutra MR,Frey A,Kraehenbuhl JP.Epithelial M cells:gateways for mucosal infection and immunization.Cell.1996;86(3):345-348.
    Neutra MR,Kozlowski PA.Mucosal vaccines:the promise and the challenge[J].Nature ReviewsImmunology,2006,6(2):148-158.
    Niethammer A.G.,Primus F.J.,Xiang R., Dolman C.S.,Ruehlmann J.M.,Ba Y.,Gillies S.D., ReisfeldR.A.,An oral DNA vaccine against human carcinoembryonic antigen (CEA) prevents growth anddissemination of Lewis lung carcinoma in CEA transgenic mice[J]. Vaccine,2001,20(3-4),421-429.
    Ning J.F.,Zhu W.,Xu J.P.,Zheng C.Y.,Meng X.L.,Oral delivery of DNA vaccine encoding VP28againstwhite spot syndrome virus in crayfish by attenuated Salmonella typhimurium[J]. Vaccine,2009,27(7),1127-1135.
    Nowotny N.,Bascunana C.R.,Ballagi-Pordaány A.,Gavier-Wideén D.,Uhleén M.,Belaák S., Phylogeneticanalysis of rabbit haemorrhagic disease and European brown hare syndrome viruses by comparison ofsequences from the capsid protein gene[J].Archives of virology,1997,142(4),657-673.
    Ohlinger V F,Haas B,Meyers G,Weiland F,Thiel H J.Identification and characterization of the virus causingrabbit hemorrhagic disease[J].Jouanal of Virology,1990,64(7):3331-3336.
    Ohlinger VF,Haas B,Thiel HJ.Rabbit hemorrhagic disease(RHD):characterization of the Causativecalicivirus[J].Veterinary Research,1993,24(2):103-116.
    Oka T,Katayama K,Ogawa S,Hansman G S,Kageyama T,Ushijima H,Miyamura T,Takeda N. ProteolyticProcessing of Sapovirus ORF1Polyprotein[J].Journal of Virology,2005,79(12):7283-7290.
    Osorio M.,Wu Y.,Singh S.,Merkel T.J., Bhattacharyya S.,Blake M.S.,Kopecko D.J.,Anthrax protectiveantigen delivered by Salmonella enterica serovar Typhi Ty21a protects mice from a lethal anthraxspore challenge[J].Infection and Immunity,2009,77(4),1475-1482.
    Paglia P,Medina E,Arioli I,Guzman CA,Colombo MP.Gene transfer in dendritic cells, induced byoral DNA vaccination with Salmonella typhimurium,results in protective immunity against amurine fibrosarcoma[J].Blood.1998.92(9):3172-3176.
    Pan Z.,Zhang X.,Geng S.,Cheng N.,Sun L.,Liu B.,Huang J.,Jiao X.,Priming with a DNA vaccine deliveredby attenuated Salmonella typhimurium and boosting with a killed vaccine confers protection ofchickens against infection with the H9subtype of avian influenza virus[J]. Vaccine,2009,27(7),1018-1023.
    Pan ZM,Jiao XA,Huang JL,Yin YL,Tang LH,Zhang H,Zhang XM,Zhang XR,Liu XF. Safety and efficacyof attenuated Salmonella typhimurium harbouring DNA vaccine against Newcastle diseasevirus[J].Wei Sheng Wu Xue Bao,2005,45(6):937-941.
    Park J.H.,Kida H.,Ueda K.,Ochiai K.,Goryo M.,Itakura C.,Etiology of rabbit haemorrhagic diseasespontaneously occurring in Korea[J].Journal of Veterinary Medicine,series B,1991,38(1-10),749-754.
    Park NY,Chong CY,Kim JH.An outbreak of viral haemorrhagic Penumonia(tentative name) of rabbits inKorea joumal of Korean veterinary medical association2003,23:603-610.
    Parkes J.P.,Norbury G.L.,Heyward R.P.,Sullivan G., Epidemiology of rabbit haemorrhagic disease(RHD)in the South Island, New Zealand,1997-2001[J].Wildlife Research2002,29(6),543-555.
    Pasetti MF,Anderson RJ,Noriega FR,Levine MM,Sztein MB.Attenuated ΔguaBA Salmonella typhiVaccine Strain CVD915as a Live Vector Utilizing Prokaryotic or Eukaryotic Expression Systems toDeliver Foreign Antigens and Elicit Immune Responses[J].Clinical Immunology,1999,92(1):76-89.
    Pathangey L.,Kohler J.J.,Isoda R.,Brown T.A.,Effect of expression level on immune responses torecombinant oral Salmonella enterica serovar Typhimurium vaccines[J]. Vaccine,2009,27(20),2707-2711.
    Pérez-Filgueira D.M., Resino-Talaván P., Cubillos C., Angulo I., Barderas M.G., Barcena J.,EscribanoJ.M.,Development of a low-cost, insect larvae-derived recombinant subunit vaccine againstRHDV[J].Virology,2007,364(2),422-430.
    Pfister T.,Wimmer E..Characterization of the Nucleoside Triphosphatase Activity of Poliovirus Protein2CReveals a Mechanism by Which Guanidine Inhibits Poliovirus Replication[J].The Journal ofBiological Chemistry,1999,274(11):6992-7001.
    Pogonka T,Klotz C,Kovacs F,Lucius R.A single dose of recombinant Salmonella typhimurium inducesspecific humoral immune responses against heterologous Eimeria tenella antigens inchicken[J].International Journal for Parasitology.2003,33(1):81-88.
    Polo J M,Dubensky T W.Virus-based vectors for human vaccine applications [J].Drug DiscoveryToday.2002,7(13):719-727.
    Prasad B,Matson D.O.,Smith AW.Three-dimensional structure of calicivirus[M].Journal of MolecularBiology,1994,240(3):256-264.
    Pütz MM,Bouche FB,de Swart RL,Muller CP.Experimental vaccines against measles in a world ofchanging epidemiology [J].International Journal for Parasitology.2003,33(5-6):525-545.
    Qu D,Wang S,Cai W, Du A.Protective effect of a DNA vaccine delivered in attenuated Salmonellatyphimurium against Toxoplasma gondii infection in mice[J].Vaccine,2008,26(35):4541-4548.
    Ramiro-Ibanez F.,Martin-Alonso J.M.,Garcia Palencia P.,Parra F.,Alonso C.,Macrophage tropism of rabbithemorrhagic disease virus is associated with vascular pathology[J]. Virus research,1999,60(1):21-28.
    Reik A,Gregory P D,Case C C.An oncolytic adenovirus armed with a GM-CSF activating designedZinc-finger protein transcription factor: a potential cancer vaccine approach [J].MolecularTherapy.2004,9(S1):S238.
    Rescigno M,Urbano M,Valzasina B,Francolini M,Rotta G,Bonasio R,Granucci F, KraehenbuhlJP,Ricciardi-Castagnoli P.Dendritic cells express tight junction proteins and penetrate gut epithelialmonolayers to sample bacteria[J]Nature immunology.2001;2(4):361-367.
    Robinson A.J.,Kirkland P.D.,Forrester R.I.,Capucci L.Cooke B.D.,Philbey A.W., Serological evidence forthe presence of a calicivirus in Australian wild rabbits, Oryctolagus cuniculus, before the introductionof rabbit haemorrhagic disease virus (RHDV): its potential influence on the specificity of acompetitive ELISA for RHDV[J]. Wildlife Research,2002,29(6),655-662.
    Robinson H L.New hope for an aids vaccine [J].Nature Reviews Immunology.2002,2(4):239-250.
    Roland K,Karaca K,Sizemore D.Expression of Escherichia coli antigens in Salmonella typhimurium as avaccine to prevent airsacculitis in chickens[J].Avian Diseases.2004,48(3):595-605.
    Romani N,Ratzinger G,Pfaller K,Salvenmoser W,St ssel H,Koch F,Stoitzner P.Migration of dendritic cellsinto lymphatics--The langerhans cell example: Routes, regulation, and relevance[J].Internationalreview of cytology.2001;207:237-270.
    Rudzki K.Esea Ped rabbit calieivirus highlights Australias chequered history of biological control[J].search1996,26:287
    Ruvoen-Clouet N.,Blanchard D.,Andre-Fontaine G.,Ganiere J.P.,Partial characterization of the humanerythrocyte receptor for rabbit haemorrhagic disease virus[J].Research in Virology.1995,146(1):33-41.
    Schirrmeier H.,Reimann I.,Kollner B.,Granzow H.,Pathogenic,antigenic and molecular properties of rabbithaemorrhagic disease virus (RHDV) isolated from vaccinated rabbits:detection and characterizationof antigenic variants[J].Archives Virology,1999,144(4),719-735.
    Scibetta AG,Copier J,Barrett A,Chaplin T,TaylorPapadimitriou J.Gene Expression changes Induced by aRecombinant E1-/E3-Adenovirus Type5Vector in Human Mammary Epithelial Cells[J].Intervirology,2005,48(6):350-361.
    Shanley J D,Wu C A.Intranasal immunization with a replication-deficient adenovirus vector expressingglycoprotein H of murine cytomegalovirus induces mucosal and systemic immunity [J].Vaccine.2005,23(8):996-1003.
    Shata MT,Reitz J MS,DeVico AL,Lewis GK,Hone DM.Mucosal and systemic HIV-1Envspecific CD8+Tcells develop after intragastric vaccination with a Salmonella Env DNA vaccine vector[J].Vaccine,2001,20(3-4):623-629.
    Shata MT,Stevceva L,Agwale S,Lewis GK,Hone DM.Recent advances with recombinant bacterialvaccine vectors[J].Molecular Medicine Today,2000,6(2):66-71.
    Shien J.H.,Shieh H.K.,Lee L.H..Experimental infections of rabbits with rabbit haemorrhagic disease virusmonitored by polymerase chain reaction[J].Research in Veterinary Science,2000,68(3):255-259.
    Sipo I,Hurtado Picó A,Wang X,Eberle J,Petersen I,Weger S,Poller W,Fechner H.An improved Tet Onregulatable FasLadenovirus vector system for lung cancer therapy [J]. Journal of MolecularMedicine,2006,84(3):215-225.
    Slimane El Mehdaoui,Antoine Touzé,Sylvie Laurent,Pierre-Yves Sizaret,Denis Rasschaert, PierreCoursaget.Gene transfer using recombinant rabbit hemorrhagic disease virus capsids with geneticallymodified DNA encapsidation capacity by addition of packaging sequences from the L1or L2proteinof human papillomavirus type16[J].Journal of Virology,2000,74(22):10332-10340.
    Somner E.A.,Ogun S.A.,Sinha K.A.,Spencer Valero L.M.,Lee J.J., Harrison J.A.,Holder A.A.,HormaecheC.E.,Khan A.C.M.,Expression of disulphi debridge dependent conformat-ional epitopes andimmunogenicity of the carboxyterminal19kDa domain of Plasmodium yoelii merozoite surfaceprotein-1in live attenuated Salmonella vaccine strains[J]. Microbiology,1999,145(1),221-229.
    Sosnovtseva S.A.,Sosnovtsev S.V.,Green K.Y..Mapping of the Feline calicivirus proteinase Responsible forAutocatalytic Processing of the Nonstructural Polyprotein and Identification of a StableProteinase-Polymerase Precursor Protein[J].Journal of Virology,1999,73(8):6626-6633.
    Stagg AJ,Kamm MA,Knight SC.Intestinal dendritic cells increase T cell expression of4β7integrin[J].European journal of immunology.2002,32(5):1445-1454.
    Studdert M.J..Rabbit haemorrhagic disease virus:a calicivirus with differences[J]. Australian VeterinaryJournal.1994,71(8):264-266.
    Sundaram RNS,Bhattacharyya AR,Nair NS,Ves M.A note on the incidence of haemorrhagic disease inrabbits in India.journal of aPPlied rabbit rescarch1991,(14):151.
    Sznol M,Lin SL,Bermudes D,Zheng L,King I.Use of preferentially replicating bacteria for the treatment ofcancer[J].The Journal of Clinical investigation,2000,105(8):1027-1030.
    Tanaji Mitra,Stanislav V. Sosnovtsev,Kim Y. Green.Mutagenesis of tyrosine24in the VPg protein is lethalfor feline calicivirus [J].Journal of Virology,2004,78(9):4931-4935.
    Tian L.,Liao J.,Li J.,Zhou W.,Zhang X.,Wang H.,Isolation and identification of a non-haemagglutinatingstrain of rabbit hemorrhagic disease virus from China and sequence analysis for the VP60Gene[J].Virus Genes,2007,35(3),745-752.
    Torres J M,Sanchez C,Ramirez M A,Morales M,Barcena J,Ferrer J,Espuna E,Pages-ManteA,Sanchez-VizcainoJ M.First field trial of a transmissible recombinant vaccine against myxomatosisand rabbit hemorrhagic disease [J].Vaccine,2001,19(31):4536-4543.
    Torres-Escobar A.,Juarez-Rodriguez M.D.,Branger C.G.,Curtiss III R.,Evaluation of the humoral immuneresponse in mice orally vaccinated with live recombinant attenuated Salmonella enterica delivering asecreted form of Yersinia pestis PsaA[J]. Vaccine,2010,28(36),5810-5816.
    Tribe DE.Run rabbit run,from Calicivirus disease.Austral.Biotech.1996:(5):335-6.
    Ueda K.,Park J.H.,Ochiai K.,Itakura C.,Disseminated intravascular coagulation (DIC) in rabbithaemorrhagic disease[J].Japanese Journal of Veterinary Research,1992,40(4),133-141.
    Uniport. http://www.uniprot.org/uniprot/P27410#PRO_0000036959
    Urashima M,Suzuki H,Yuza Y,Akiyama M,Ohno N,Eto Y.An oral CD40ligand gene therapy againstlymphoma using attenuated Salmonella typhimurium[J].Blood,2000,95(4):1258-1263.
    Valicek L.,Smid B.,Rodak L.,Kudrna J.,Electron and immunoelectron microscopy of rabbit haemorrhagicdisease virus(RHDV)[J].Archives of Virology,1990,112(3-4):271-275.
    Vazquez-Torres A,Fang FC.Cellular routes of invasion by enteropathogens[J].Current Opinion inMicrobiology,2000,3(1):54-59.
    Viaplana E,Plana J,Villaverde Z.Antigenicity of VP60structural protein of rabbit hemorrhagic diseasevirus[J].Aich Virol,1997,142(9):1843-1848.
    Wang L.,Curd H.,Reeves P.R.,Immunization of mice with live oral vaccine based on a Salmonella enterica(sv Typhimurium) aroA strain expressing the Escherichia coli O111O antigen[J].MicrobialPathogenesis1999,27,55-59.
    Wang X.,Qiu L.,Hao H.,Zhang W.,Fu X.,Zhang H.,He S.,Zhang S.,Du E.,Yang Z., Adenovirus-based oralvaccine for rabbit hemorrhagic disease[J].Veterinary Immunology and Immunopathology,2012,145(1-2):277-282.
    Wang XW,Jiang WM,Jiang P,Li YF,Feng ZX,Xu JR.Construction and immunogenicity of recombinantadenovirus expressing the capsid protein of porcine circovirus2(PCV2) in mice[J].Vaccine,2006,24(16):3374-3380.
    Wenge Ma,Li Yu. Analysis of two VP60capsid protein genes of rabbit hemorrhagic disease virus fromviruses obtained from the same farm.Archives of virology,2010,155(9):1497-1501.
    Wirblich C,Sibilia M,Boniotti M B,Rossi C,Thiel H J,Meyers G.3C-like protease of rabbit hemorrhagicdisease virus:identification of cleavage sites in the ORF1polyprotein and analysis of cleavagespecificity[J].Journal of Virology,1995,69(11):7159-7168.
    Wirblich C,Thiel H J,Meyers G.Genetic map of the calicivirus rabbit hemorrhagic disease virus as deducedfrom in vitro translation studies[J].Journal of Virology,1996,70(11):7974-7983.
    Woo PCY,Wong LP,Zheng BJ,Yuen KY.Unique immunogenicity of hepatitis B virus DNA vaccinepresented by live-attenuated Salmonella typhimurium[J].Vaccine,2001,19(20-22):2945-2954.
    Xie C,He JS,Zhang M,Xue SL,Wu Q,Ding XD,Song W,Yuan Y,Li DL,Zheng XX,Lu YY,Shang Z,TherapyHG. Oral Respiratory Syncytial Virus(RSV)DNA Vaccine Expressing RSV F protein Delivered byAttenuated Salmonella typhimurium[J].Human Gene Therapy,2007,18(8):746-752.
    X-W Ren,M Liang,X Meng,X Ye,H Ma,Y Zhao,J Guo,N Cai H-Z Chen,S-L Ye,F Hu.A tumor-specificconditionally replicative adenovirus vector expressing TRAIL for gene therapy of hepatocellularcarcinoma [J].Cancer Gene Therapy,2006,13(2):159-168.
    Yang H,Cao SJ,Huang XB,Liu JW,Tang Y,Wen XT. Intragastric administration of attenuated Salmonellatyphimurium harbouring transmissible gast roenteritis virus (TGEV)DNA vaccine induced specificantibody production[J].Vaccine,2009,27(37):5035-5040.
    Yang P.L.,Althage A.,Chung J.,Maier H.,Wieland S.,Isogawa M.,Immune effectors required for hepatitis Bvirus clearance[J].Proceedings of the National Academy of Sciences,2010,107(2),798-802.
    Yang Y.,Zhang Z.,Yang J.,Chen X.,Cui S.,Zhu X.,Oral vaccination with Ts87DNA vaccine delivered byattenuated Salmonella typhimurium elicits a protective immune response against Trichinella spiralislarval challenge[J]. Vaccine,2010,28(15):2735-2742.
    Yoshikazu Yuki,Tomonori Nochi,Hiroshi Kiyono.Progress towards an AIDS mucosal vaccine: anoverview[J].Tuberculosis.2007,87:S35-S44.
    Yuhua L,Kunyuan G,Hui C,Yongmei X,Chaoyang S,Xun T,Daming R.Oral cytokine gene therapy againstmurine tumor using attenuated Salmonella typhimurium[J].International Journal of Cancer,2001,94(3):438-443.
    Yuki Y,Kiyono H.New generation of mucosal adjuvants for the induction of protective immunity[J].Reviews in medical virology.2003,13(5):293-310.
    Zhang Q.,Ma Q.,LiQ.,YaoW.,Wang C.,Enhanced protection against nasopharyngeal CarriageofStreptococcus pneumoniae elicited by oral multiantigen DNA vaccines delivered in attenuatedSalmonella typhimurium[J].Molecular Biology Reports,2011,38(2),1209-1217.
    Zhang QY,Jin YZ,Zhang HB,Xie SS.Construction and biological activities of CTLA4Ig adenovirusvectors[J].Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi,2003,19(1):45-48.
    Zhao Z.,Li M.,Luo D.,Xing L.,Wu S.,Duan Y.,Yang P.,Wang X.,Protection of mice from Brucella infectionby immunization with attenuated Salmonella enterica serovar typhimurium expressing A L7/L12andBLS fusion antigen of Brucella[J].Vaccine,2009,27(38),5214-5219.
    Zheng D.,Xue T.,Chen D.,Zheng M.,Zhou Z.,Xu W.,Three-dimensional,structure of the wild-typeRHDV[J]. Chinese Science Bulletin,2001,46(12),1005-1008.

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