Immuno-Protective Efficiency of the Bivalent Inactivated Vaccine Against Vibrio scophthalmi and Aeromonas salmonicida Infections in Turbot(Scophthalmus maximus L.)

Vibrio scophthalmi and Aeromonas salmonicida can cause high turbot mortality and huge economic losses.Presently,vaccination is the most promising method for preventing communicable diseases.In this study,we used formalin to kill V.scophthalmi and A.salmonicida cells,and mixed with the mineralized oil adjuvant(Montanide^(TM)ISA 763 AVG)to prepare the bivalent inactivated vaccine.The results showed that turbot inoculated with the bivalent inactivated vaccine exhibited strong tolerance to the infection of V.scophthalmi and A.salmonicida,and no obvious clinical symptoms and pathological changes were observed.The activities of enzymes lysozyme,acid phosphatase and complement C3 had significantly increased after the vaccination.The antibody titer response of vaccinated turbot was greatly boosted,which was positively connected with the immunological impact according to ELISA results.Simultaneously,the expression levels of immune-related genes such as MHC-IIα,MHC-IIβ,CD4,CD8,TNF-αand IL^(-1)βwere up-regulated,demonstrating that it might stimulate humoral and cellular immunological response in turbot.These findings highlight the potential of the bivalent inactivated vaccine for controlling V.scophthalmi and A.salmonicida infections in turbot.

Effectiveness of Hemorrhagic Fever with Renal Syndrome Bivalent Vaccine in China:A Metaanalysis

Objective To evaluate the effectiveness of Hemorrhagic Fever with Renal Syndrome(HFRS) bivalent vaccine in field.Methods The articles on effectiveness of HFRS bivalent vaccine were retrieved from Vip Database,China Journal Full-text Database,Wanfang database,China Hospital Knowledge Database,Chinese Biomedical Literature Database,MEDLINE and ProQuest.Two persons extracted data and evaluated the quality of data together for meta-analysis.Results Seven articles were included into the analysis,and two articles were random clinical trials,five were quasi-trials.Meta-analysis showed that the overall effectiveness of HFRS bivalent vaccine was 85%(95%confidence interval:53%-95%) within one year after vaccination,and the effectiveness in two-dose recipients and three-dose recipients was 87%(95%confidence interval:54%-96%) and 60%,respectively;it was 96%(95%confidence interval:78%-99%) within 2-5 years after vaccination,and the effectiveness in two-dose recipients and three-dose recipients was 95%(95%confidence interval:19%-100%) and 96%(95%confidence interval:70%-99%),respectively;it was 100%(only one article included) within 6-9.6 years after vaccination.The effectiveness in two-dose recipients was 88%(95%confidence interval:62%-96%) during 1-2.5 years after vaccination,and that in three-dose recipients was 94%(95%confidence interval:70%-99%) during 1-5 years after vaccination.Conclusions HFRS bivalent vaccine is effective in field,and there is no difference between two-dose recipients and three-dose recipients.We should do some further studies on the long-term effectiveness of HFRS bivalent vaccine and on the age of vaccine reception.

Observation on the Efficiency of the Mongolian Gerbil Kidney Tissue Culture Inactivated Bivalent Vaccine for Hemorrhagic Fever with Renal Syndrome

The Z 10 and Z 37 strains of hemorrhagic fever with renal syndrome (HFRS) virus and the Mongolian gerbil ( Merions unguiculatus ) kidney cells were used to prepare the inactivated bivalent vaccine. A phase Ⅱ clinical trial use of this vaccine was made in 750 Chinese volunteers. The results showed that the side reaction rate was 2.5% and the sero-conversion rate of neutralizing antibodies against Hantaan and Seoul viruses in the inoculated volunteers were 87.6% and 96.3% respectively.

Construction of a bivalent vaccine candidate against HAdV4/HAdV7 based on capsid-display strategy via Red-homologous recombination and counter-selection methodology

Human adenoviruses(HAdvs)are major respiratory pathogens.Specifically,human adenovirus type 4(HAdV4)and human adenovirus type 7(HAdV7)are known for causing fever and pneumonia,with docu-mented cases of fatalities among the population.In recent years,HAdV4/HAdv7 has been implicated in caus-ing substantial outbreaks,leading to increased morbidity in multiple countries.Most HAdV4 and HAdV7 infections have been reported in North America,Asia,Europe,Africa,South America,Oceania,and the Middle East.Most fatalities occurred in North America(the United States)and Asia(China and Singapore).Engineered recombinant adenoviruses have played a crucial role as vaccine vectors.In this study,we con-structed a recombinant adenovirus,Ad4ITRmut-Ad7E3,and evaluated it in vitro and in vivo.We observed that the replication rate of Ad4ITRmut-Ad7E3 was lower than that of the RI-67 strain,indicating that the mutation of inverted terminal repeats(ITRs)weakened the replication ability of HAdV4.Immunization of BALB/c mice with the bivalent Ad4ITRmut-Ad7E3 vaccine strain,administered by intraperitoneal injection and oral gavage,resulted in the elicitation of neutralizing antibodies targeting HAdV4 and HAdv7.This finding not only pro-vides a novel method and technique for the efficient construction of a polyvalent recombinant adenovirus vac-cine candidate against HAdV4 and HAdv7 but also against other prevalent adenovirus serotypes such as HAdV3,HAdV11,HAdV14,and HAdv55,from various regions.

Safety,immunogenicity,and preliminary efficacy of a randomized clinical trial ofomicron XBB.1.5-containing bivalent mRNA vaccine

Periodically updating coronavirus disease 19(COVID-19)vaccines that offer broad-spectrum protection is needed giventhe strong immune evasion by the circulating omicron sublineages.The effectiveness of prototype and BA.4/5-containing bivalent mRNA vaccines is reduced when XBB subvariants predominate.We initiated an observer-blinded,threearms study in 376 patients in Chinese individuals aged from 18 to 55 years old who had previously received three dosesCOVID-19 vaccine.Immunogenicity in terms of neutralizing antibodies elicited by a 30-mg dose of XBB.1.5-containingbivalent vaccine(RQ3027),a 30-mg dose of BA.2/BA.5-Alpha/Beta bivalent vaccine(RQ3025)and their precedent 30-mg Alpha/Beta(combined mutations)monovalent mRNA vaccine(RQ3013)and safety are primary and secondary endpoints,respectively.We recorded prescribed COVID-19 cases to explore the preliminary efficacy of three vaccines.RQ3027 and RQ3025 boosters elicited superior neutralizing antibodies(NAbs)against XBB.1.5,XBB.1.16,XBB.1.9.1,and JN.1 compared to RQ3013 at day 14 in participants without SARS-CoV-2 infection.All study vaccines were welltolerated without serious adverse reactions identified.The incidence rates per 1000 person-years of COVID-19 casesduring the 2nd-19th week after randomization were lowest in RQ3027.Overall,our data show that XBB.1.5-containingbivalent booster generated superior immunogenicity and better protection against newer severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants compared to BA.2/BA.5-containing bivalent and Alpha/Beta monovalentwith no new safety concerns.

表达鸡传染性喉气管炎病毒gD蛋白的重组嵌合型新城疫病毒La Sota株的构建

为构建表达鸡传染性喉气管炎病毒(ILTV)糖蛋白D(gD)的重组新城疫病毒(NDV)La Sota株,本研究将ILTV强毒株gD基因胞外域与NDV F基因信号肽、跨膜域和胞质尾区融合,并插入到含有NDV基因VII型F和HN基因的嵌合型La Sota株感染性cDNA克隆pLa Sota-VIIF/HN的P和M基因之间,将获得的重组感染性克隆pLa Sota-VIIF/HN-gD与辅助质粒pCIneo-NP-P-L共转染BHK-21细胞,拯救出表达gD蛋白的重组嵌合型NDV La Sota株rLaSota-VIIF/HN-gD,并采用血凝试验鉴定正确后,将重组病毒在9日龄SPF鸡胚中连续传至10代,提取10代重组病毒基因组RNA,反转录成c DNA作为模板,以ILTV gD基因插入位点两侧的鉴定引物进行PCR鉴定;采用第10代重组病毒感染BHK-21细胞,以ILTV gD蛋白多克隆抗体作为一抗进行间接免疫荧光试验(IFA);分别对鸡红细胞吸附的重组病毒感染的鸡胚尿囊液上清和从红细胞上解离下来的纯化的重组NDV病毒粒子经western blot鉴定,并对重组病毒对鸡胚的致病性和在鸡胚中的复制动态进行初步研究。PCR结果显示ILTV gD基因能够在重组病毒中稳定存在;IFA和western blot鉴定结果显示,重组病毒能够正确表达ILTV的gD蛋白,而且gD蛋白嵌合表达在重组病毒颗粒上。鸡胚致病性试验和鸡胚中的复制动态试验结果显示,重组病毒保持了La Sota疫苗株的低致病性和良好的复制特性,rLaSota-VIIF/HN-gD的鸡胚平均死亡时间(MDT)为168 h,1日龄雏鸡脑内接种该重组病毒的致病指数(ICPI)为0.20,鸡胚半数感染量(EID_(50))峰值可达10^(-8.66)/100μL。本研究所制备的重组病毒r LaSota-VIIF/HN-gD为研制基因VII型NDV和ILTV的二联活疫苗奠定了基础。

Modification in Media Composition to Obtain Secretory Production of STxB-based Vaccines using Escherichia coli

Shiga toxin B-subunit （STxB） from Shigella dysenteriae targets in vivo antigen to cancer cells, dendritic cells （DC） and B cells, which preferentially express the globotriaosylceramide （Gb3） receptor. This pivotal role has encouraged scientists to investigate fusing STxB with other clinical antigens. Due to the challenges of obtaining a functional soluble form of the recombinant STxB, such as formation of inclusion bodies during protein expression, scientists tend to combine STxB with vaccine candidates rather than using their genetically fused forms. In this work, we fused HPV16 E7 as a vaccine candidate to the recombinantly-produced STxB. To minimize the formation of inclusion bodies, we investigated a number of conditions during the expression procedure. Then various strategies were used in order to obtain high yield of soluble recombinant protein from E. coli which included the use of different host strains, reduction of cultivation temperature, as well as using different concentrations of IPTG and different additives （Glycin, Triton X-100, ZnC12）. Our study demonstrated the importance of optimizing incubation parameters for recombinant protein expression in E. coli; also showed that the secretion production can be achieved over the course of a few hours when using additives such as glycine and Triton X-100. Interestingly, it was shown that when the culture mediums were supplemented by additives, there was an inverse ratio between time of induction （TOI） and the level of secreted protein at lower temperatures. This study determines the optimal conditions for high yield soluble E7-STxB expression and subsequently facilitates reaching a functionally soluble form of STxB-based vaccines, which can be considered as a potent vaccine candidate for cervical cancer.

Lessons from Vibrio Pathogen and the Comparative Study of Vaccines Developed

Cholera continues to be one of the most common causes of morbidity and mortality among children and adults in developing countries. Vaccine against cholera is an approach in the control of this epidemic and pandemic disease. From the development of very early oral cholera vaccine, advances in vaccine development documented due to a good illustration of the epidemiology, outbreak strategy, and pathophysiology of the disease causing pathogen. The newer-generation oral cholera vaccines are safe and guarantee a high level of protection during outbreak settings for several years. Yet infants and young children in developing countries are hyporesponsive to vaccines and show poor protection against cholera. In this review, we survey and analyse our current knowledge on the etiology of cholera, its clinical manifestation, global epidemiology and elaborate the vaccine candidates, which are effective against the pathogen and the corresponding immune responses to the available vaccines. These reviews comprehensively cover the salient features of recent discoveries related to Vibrio cholerae virulence, past and present vaccine candidates and their advantages and disadvantages with their development strategies. We believe that the advances that have been included in this review will give a comprehensive insight to the prevention and control of cholera outbreaks and development of effective cholera vaccines.

基于悬浮细胞制备的鸡新城疫-H9亚型禽流感二联灭活疫苗(La Sota株+BX13株)安全性和免疫产生期研究

为探讨悬浮细胞制备的鸡新城疫-H9亚型禽流感二联灭活疫苗(La Sota株+BX13株)(以下简称二联灭活疫苗)的安全性和免疫产生期,试验用新城疫病毒(NDV)La Sota株和H9亚型禽流感病毒(AIV)BX13株分别接种BHK-21和MDCK悬浮细胞,收获抗原液,制备二联灭活疫苗;采用1 mL/只的剂量接种21日龄SPF鸡进行二联灭活疫苗的安全性试验;以0.02、0.05、0.1、0.3、0.5 mL/只的剂量接种21日龄SPF鸡,免疫后7、14、21 d采血测定NDV HI和AIVHI抗体,并于免疫后21日龄攻毒进行免疫保护试验和免疫产生期试验。结果显示:二联灭活疫苗对SPF鸡安全,鸡只无不良反应,疫苗吸收良好;各剂量组免疫后抗体水平均逐渐升高,免疫后21 d NDV HI效价为6.1~8.5 log2,AIV HI效价为7.5~11.2 log2;免疫后21 d,0.02 mL/只剂量组对两种毒株的攻毒保护率均为9/10,其余剂量组均为10/10保护。研究表明,二联灭活疫苗对SPF鸡安全,以0.1 mL/只的剂量免疫SPF鸡21 d可获得对NDV和H9 AIV的有效抵抗。

猪瘟活疫苗-猪口蹄疫O型、A型二价灭活疫苗联合免疫效果的评价

为建立一种既有效又简便的猪瘟活疫苗(CSF)和猪口蹄疫O型、A型二价灭活疫苗(FMD O-A)联合免疫方法,达到“一针多防”的目的,通过动物免疫试验,评价了CSF和FMD O-A联合免疫的可行性。采用左、右各一针同步2点接种试验猪群(联合免疫),以2种疫苗分别单独免疫的猪群为对照,在免疫前0 d、免疫后14、40、60和90 d采集血清检测2种疫苗对应的抗体。经统计学分析发现,2种疫苗的联合免疫不影响其抗体的产生,并且能够保持抗体在猪群个体间的稳定分布。

洼地绵羊羔羊O型口蹄疫疫苗免疫程序的优化

为优化洼地绵羊羔羊O型口蹄疫疫苗免疫程序,为洼地绵羊口蹄疫综合防控措施的制定提供参考依据,试验采用阻断ELISA方法分析了羔羊母源抗体消长规律、不同剂量疫苗免疫抗体消长规律、疫苗加强免疫不同间隔时间抗体消长规律。结果显示:(1)随着羔羊月龄的逐渐增加,其体内的母源抗体效价迅速降低,3月龄的母源抗体效价已经远远低于完全保护性抗体效价(1∶128);(2)在疫苗免疫后14 d、21 d、28 d、60 d、90 d、120 d、150 d、180 d、210 d,双倍剂量组的抗体效价均显著高于单倍剂量组(P<0.05);(3)在疫苗首免后90 d、120 d、150 d、180 d、210 d,加强免疫间隔1个月组的抗体效价均显著高于间隔半个月组(P<0.05)。确定该羊场羔羊的最佳免疫程序为:羔羊3月龄免疫O型口蹄疫灭活疫苗双倍剂量,首免后间隔1个月加强免疫O型口蹄疫灭活疫苗。

2014—2022年榆林市猪O型口蹄疫免疫效果监测及影响因素分析

研究旨在系统评估榆林市猪O型口蹄疫免疫成效,采用采样检测与追溯调查相结合的方法,对2014—2022年榆林市的猪O型口蹄疫疫苗免疫抗体水平及其影响因素进行了监测与系统分析。结果显示:2014—2022年榆林市猪O型口蹄疫免疫抗体合格率平均为80.9%,均达到农业农村部规定的不低于70%的标准,但是2019年、2020年散养户猪O型口蹄疫免疫抗体合格率分别为56.3%和66.7%,2014年、2019年规模猪场抗体合格率均为75.7%。研究表明,抗体水平不合格或是不够高的主要原因包括无加强免疫、免疫与采样监测间隔时间过长或过短、疫苗保存或使用不当、免疫操作不规范以及猪群健康情况等。

Immunization effect of purified bivalent vaccine to haemorrhagic fever with renal syndrome manufactured from primary cultured hamster kidney cells

Haemorrhagic fever with renal syndrome (HFRS) is a worldwide epidemic plaguing over thirty nations. This disease has spread across 26 provinces, cities and autonomous regions of China with an annual onsets number of more than a hundred thousand and a mortality rate of 5% to 15%, accounting for over 80% of cases in the world, and threatening the safety and health of Chinese people. 1 Analysis of serum samples over recent years indicates that the plagued areas are expanding. Instead of a single type Ⅰ or Ⅱ strain, each area now has a combination with one type predominant. 2 These demographic changes revealed a shortcoming of the monovalent vaccine in use, urging China to develop a purified bivalent vaccine based on monovalent one. This research on clinical observation and immunization effects led to a purified bivalent vaccine manufactured by Changchun Institute of Biological Products, China from primary cultured hamster kidney cells.

日本血吸虫双价DNA疫苗pVIVO2-Sj14-Sj23免疫方案的研究

目的研究双价DNA疫苗pVIVO2-Sj14-Sj23在不同免疫剂量、免疫次数、免疫有效时间及不同免疫途径的最佳免疫方案。方法构建和制备双价DNA疫苗pVIVO2-Sj14-Sj23;110只雄性BALB/c小鼠随机分成11组,每组10只,按照四因素三水平分成2个对照组和9个实验组。各组统一在末次免疫后30d每鼠感染(40±2)条日本血吸虫尾蚴,感染后45d剖杀,计数成虫虫荷。结果双价DNA疫苗9个实验组获得40.14%～62.68%的减虫率。通过SPSS12.0进行正交设计的统计分析:F值<F′临界值,P>0.05。免疫剂量,免疫次数,免疫途径和免疫有效时间几个因素间差异无统计学意义。结论实验结果提示该疫苗的较好免疫方案为:50μg/只,免疫2次,采取皮内注射,免疫有效时间至少为12周。

副溶血弧菌(Vibrio parahaemolyticus)tdh2基因和鳗弧菌(V.anguillarum)ompU基因二联DNA疫苗制备及其对大菱鲆(Scophthalmus maximus)免疫保护作用

采用基因工程的方法,将副溶血弧菌的热稳定直接溶血素基因tdh2和鳗弧菌外膜蛋白基因ompU进行融合,在大肠杆菌中得到表达,并利用该融合基因构建二联DNA疫苗pEGFP-N1/tdh2-ompU。用DNA疫苗按10和50μg/尾的剂量通过肌肉注射免疫大菱鲆,对大菱鲆抵抗致病性副溶血弧菌和鳗弧菌的免疫效果进行研究。结果表明,DNA疫苗免疫的大菱鲆对副溶血弧菌感染的最高保护率为100%,对鳗弧菌感染的保护率为35%。被免疫的大菱鲆肌肉组织中能检测到融合蛋白表达,在血清中能检测到较高水平特异性抗体,DNA疫苗引起的体液免疫反应水平和保护效果与注射剂量有关。

表达霍乱CT-B和LPS-O抗原的鼠伤寒菌苗株的构建

将编码霍乱ＣＴＢ和ＬＰＳＯ抗原的基因与载体质粒ｐＹＡ２４８重组后，转入ΔｃｙａΔｃｒｐΔａｓｄ减毒鼠伤寒疫苗株ｘ４０７２，构建成无药物抗性、带双价抗原的工程菌株ｘ４０７２（ｐＭＧ３０６）。该菌株能分泌表达特异的霍乱ＣＴＢ抗原，并且在菌体表面同时表达霍乱和鼠伤寒的Ｏ抗原。小鼠腹腔免疫和攻击试验表明该菌苗株对霍乱毒株的攻击具有良好的保护作用。

鳗弧菌O1/O2二价灭活疫苗免疫大菱鲆的抗体持续期和免疫保护期

本研究分析了鳗弧菌(Vibrio anguillarum)O1/O2血清型二价灭活疫苗免疫大菱鲆后的抗体持续期和免疫保护期。以鳗弧菌O1血清型VAM003株和O2血清型VAM007株为抗原制备了福尔马林灭活二价疫苗,将疫苗按照三种剂量(10~7 cells/尾、10~8 cells/尾、10~9 cells/尾)以腹腔注射途径免疫大菱鲆,在免疫后3 d、7 d、14 d、30 d、60 d、90 d、120 d、150 d,用血清凝集实验检测了免疫鱼血清的VAM003和VAM007抗体效价,用攻毒实验检测了疫苗的免疫保护率(RPS)。结果显示,在免疫后7 d三个剂量组的大菱鲆均产生了特异抗体,并获得27%～60%的RPS。三个剂量组大菱鲆的O1血清型抗体持续期分别>90 d (10~7 cells/尾组)、>150 d (10~8 cells/尾组)、>150 d (10~9cells/尾组),而三个剂量组大菱鲆的O2血清型抗体持续期均>150 d。三个剂量组的大菱鲆获得的免疫保护持续期均>150 d;以RPS>75%为有效免疫保护,各剂量组大菱鲆抵抗O1血清型病原感染的有效免疫保护期为:14～120d(10~7 cells组)、14～120 d (10~8 cells/尾)、14～150 d (10~9 cells/尾),抵抗O2血清型病原感染的有效免疫保护期为:14～60 d (10~7 cells组)、14～120 d (10~8 cells/尾)、14～120 d (10~9 cells/尾)。研究结果表明鳗弧菌二价灭活疫苗可为大菱鲆提供有效而稳定的免疫保护,获得的抗体持续期和免疫保护期为该疫苗的临床中试研究提供了基础。

Mucosal immune responses and protective efficacy in yellow catfish after immersion vaccination with bivalent inactivated Aeromonas veronii and Edwardsiella ictaluri vaccine

Mucosal vaccination,which has the potential to induce both mucosal and systemic immune responses,is considered the most suitable method of preventing infectious diseases in farmed fish.Aeromonas veronii and Edwardsiella ictaluri are two pathogenic bacteria found in yellow catfish and often infect the fish through mucosal surfaces.Delivery of a bivalent inactivated vaccine by injection has been shown to induce a strong systemic immune response against both bacterial infections.However,mucosal immune responses and protective efficiency induced by this inactivated vaccine administrated via immersion are yet to be investigated.We developed a bivalent vaccine containing formalin-inactivated A.veronii and E.ictaluri and evaluated the immune response in yellow catfish after immersion vaccination using body fluids biochemistry indices,agglutinating antibody titers,and the expression level of immune-related genes in the skin,gills,spleen,and head kidney.The activities of innate immune-related enzymes and specific agglutination antibody titers in body fluids,as well as the expression of innate and adaptive immune-related genes in both the mucosal and systemic tissues of vaccinated fish,were significantly higher than that in control fish.Next,we assessed the protective efficacy by a challenge model of virulent strains of E.ictaluri and A.veronii.The relative survival percent of vaccinated fish was 80%and 87%after challenging fish with E.ictaluri and A.veronii,respectively,which was higher than unvaccinated control fish(43%and 57%).These results confirm that the bivalent inactivated vaccine administered via immersion induces a strong mucosal immune response and confers good protection against both E.ictaluri and A.veronii.Our results also reinforce the notion that immersion vaccination could stimulate both mucosal and systemic immunity contributing to protection against pathogens.

猪口蹄疫O型合成肽疫苗抗体水平检测

为了解猪口蹄疫O型合成肽疫苗的免疫效果,选用了两个厂家生产的猪口蹄疫O型合成肽疫苗,对80头试验仔猪进行了免疫注射,并在6、7、8、9、11、13、20周龄采血,通过ELISA检测抗体水平的变化。结果显示,猪口蹄疫O型合成肽疫苗能快速诱导产生高水平的抗体;疫苗的免疫副作用小;使用VP1ELISA和LPB-ELISA检测猪口蹄疫O型合成肽疫苗免疫抗体试验相关性较好。

猪O型FMDV重组多表位抗原基因的克隆表达及免疫学鉴定

【目的】制备猪O型FMDV广谱多表位疫苗,并筛选最适合的免疫佐剂.【方法】选取O型FMDV 3个毒株VP1蛋白的优势表位,设计并合成重复串联表位基因3FoEN2,并克隆猪IgG重链恒定区基因.利用BamHⅠ,EcoRⅠ等位点将2个基因依次克隆到pProEX-HTb载体,构建重组质粒pE-IgG并转化大肠杆菌BL21(DE3)感受态细胞.以IPTG诱导表达得到融合蛋白pE-IgG,经SDS-PAGE电泳分析,Western-blotting鉴定.分别用5种佐剂ISA206、ISA201、IMS1313、603、ISA61乳化融合蛋白配制疫苗免疫BALB/c雌鼠,间接ELISA方法测定抗体水平.【结果】重组蛋白以包涵体形式正确表达,大小为45kU,且能与感染O型FMDV的猪的阳性血清发生特异性免疫反应;ISA201佐剂试验组刺激机体产生的抗体水平最高.【结论】pE-IgG蛋白具有很强的免疫原性,与ISA201佐剂混合制备成的猪O型口蹄疫病毒多表位疫苗可刺激动物机体产生高水平抗体,是具有良好开发前景的疫苗.