国内外猪源产肠毒素大肠杆菌疫苗研究进展

仔猪腹泻是全球规模化猪场最常见的疾病之一,给养猪业带来了巨大的损失。产肠毒素大肠杆菌（ETEC）是引起仔猪腹泻的主要病原菌,黏附素和肠毒素是其重要的致病因子,ETEC通过黏附素定植于小肠上皮细胞,在增殖过程中不断产生肠毒素,引起大量水和电解质进入肠腔,导致仔猪腹泻。目前,疫苗免疫是预防ETEC最有效的方法,然而许多商品化大肠杆菌疫苗的临床免疫效果不佳,且地域局限性明显。因此,研制安全、高效、广谱的ETEC疫苗对养猪业具有重要意义。近年来,许多新型试验性ETEC疫苗被相继报道,如ETEC菌毛黏附素和肠毒素疫苗;一些新开发的疫苗,如亚单位疫苗、菌影疫苗、植物载体疫苗和囊泡疫苗等,具有不同的优势,在不同的动物试验中均表现出良好的免疫保护效果。文章简述了国内外学者在ETEC疫苗领域的研究进展,对猪源ETEC各类疫苗的优劣及应用研究情况进行了综述,以期为今后猪源ETEC疫苗的研究提供参考。     

产肠毒素大肠杆菌疫苗在断奶仔猪中的应用

产肠毒素大肠杆菌(ETEC)是引起新生仔猪和断奶仔猪腹泻的主要病原之一。通过免疫母猪,新生仔猪通常可以从初乳和乳汁得到有效保护,但在断奶阶段,母乳的保护消失。有关研究发现,引起断奶仔猪腹泻常见的ETEC菌株均有菌毛F4或F18。这些菌毛是重要的毒力因子,它们使细菌结合到宿主易感肠上皮细胞,在肠内定植繁殖,随后分泌肠毒素引起腹泻。文章针对由菌毛F4和/或F18产毒素大肠杆菌引起的腹泻,概括了在养猪生产中其相关免疫接种途径,包括口服弱毒苗和亚单位疫苗、胶囊疫苗和注射免疫接种等。     

大肠杆菌表达的融合蛋白VP4-STI的免疫效果研究

研究表明，肠毒素是ETEC致幼畜腹泻的根本原因，由ETEC产生的肠毒素包括热敏感肠毒素（LT）和热稳定肠毒素（ST），其中ST又包括STⅠ和STⅡ。调查表明，几乎所有的腹泻幼畜只要分离到ETEC．大部分都产生STⅠ。但是，由于STⅠ的分子质量太小，几乎没有免疫原性，因此，通过基因融合的方式借助大分子物质提高STⅠ的免疫原性是当前国内外学者致力于ETEC疫苗开发的重点。轮状病毒系呼肠孤病毒科（Reoviridae）轮状病毒属（Rotavirus）的成员，是致幼畜病毒性腹泻最主要的病原体，其中外膜蛋白VP4不仅是轮状病毒血清学分型的依据，而且是主要的保护性抗原。     

产肠毒素性大肠杆菌疫苗研究概况

产肠毒素性大肠杆菌（简称ETEC）是引起仔猪腹泻的主要病原之一。在家畜中,尤以初生幼畜特别易感。并引起生长发育迟缓,生产能力低下,甚至造成死亡。给畜牧业造成很大损失。ETEC肠毒素基因和菌毛蛋白（黏附素）基因对于ETEC的致病性起主要作用。除了灭活疫苗、减毒疫苗、结合多糖疫苗和亚单位疫苗外,新近出现的DNA疫苗、转基因植物疫苗为疫苗的研制提供了新的思路。本文概述并评价了各类产肠毒素性大肠杆菌疫苗．并简要介绍了产肠毒素性大肠杆菌疫苗最新的进展。     

猪源大肠杆菌热稳定肠毒素的检测

致病性大肠杆菌产生一种或多种肠毒素称为肠毒素型大肠杆菌(Enterotoxigenic E．COLI ETEC)．ETEC是引起幼畜腹泻的重要病原菌。ETEC能借助于所产生的菌毛抗原粘附于动物小肠黏膜。定居并产生作用于肠壁的外毒素，称为肠毒素。主要有两类肠毒素：一类是不耐热性肠毒素即热敏感肠     

抗仔猪腹泻产肠毒素大肠杆菌疫苗的研究进展

仔猪腹泻(piglet diarrhea)是国内外养猪业面临的一大难题,每年因此造成的经济损失十分巨大。导致仔猪腹泻的主要致病菌是产肠毒素大肠杆菌(enterotoxigenic Escherichia coli,ETEC),其致病过程依赖黏附素和肠毒素的共同作用。随着研究手段的创新,国内外学者在研制ETEC疫苗方面已取得了突破性进展。作者介绍了ETEC的致病特点,并对各类ETEC疫苗的研究进展作一综述。     

产肠毒素大肠杆菌菌毛的DNA疫苗研究进展

肠毒素大肠杆菌是导致婴幼儿及旅游者急性腹泻,仔猪腹泻和水肿的主要病原菌之一。菌毛定居因子是该病原菌主要的致病因素。DNA疫苗既能激发机体的细胞免疫,也能诱导特异性的体液免疫。目前用于预防ETEC腹泻的DNA疫苗的研究已取得一定进展,作者从重组质粒的构建、免疫应答、疫苗的接种系统以及基因佐剂4个方面简单的概述了产肠毒素大肠杆菌菌毛的DNA疫苗的研究现状。     

产肠毒素大肠杆菌主要致病因子及其致病机理的研究进展

仔猪腹泻是畜牧业养殖的主要问题之一,每年在世界范围内造成极大的经济损失。肠毒素大肠杆菌(enterotoxigenicescherichia coli,ETEC)是引起仔猪腹泻的主要病原之一〔1〕。肠毒素大肠杆菌致病因子包括:粘附素(adhesion)、肠毒素(Enterotoxins)、水肿病毒素(edema disease princ     

大肠杆菌表达的融合蛋白K88ac-STⅡ的免疫效果

产肠毒素大肠杆菌（enterotoxigenic escherichiacoli，ETEC）是引起幼畜腹泻的病原菌，感染病畜发病快，死亡率高。研究表明，病原菌ETEC的致病过程包括菌毛粘附因子对小肠上皮细胞的粘附和致腹泻毒素的产生，其中，菌毛粘附是其致病的始动因素，毒素是其致病的直接原因。所以，研制针对菌毛和毒素的多价疫苗理论上可以有效地预防幼畜腹泻。据调查，     

产肠毒素大肠杆菌毒力变化的原因简述

产肠毒素性大肠杆菌(Enterotoxigenic Escherichia Coli,ETEC)感染是幼龄动物(主要是猪和小牛)大肠杆菌病的最常见型,是引起发展中国家旅行者和儿童腹泻的重要原因。ETEC的主要毒力属性是黏附素和肠毒素,它们主要受大型质粒的调节。研究表明,几乎所有的ETEC细菌都可以通过它们的蛋白表面附属物(菌毛、菌毛)或通过非膜蛋白黏附在动物小肠上皮的受体上,而且不引起显著的形态学改变。此外,它们可分泌蛋白毒素(肠毒素),以减少营养吸收以及增加小肠上皮细胞液体和电解质的分泌。读者可参考较早的更为广泛的综述(Nagy和Fekete,1999)了解有关动物ETEC感染和腹泻的流行病学、发病机制、诊断和预防的细节。本文旨在总结相关基本知识,并着重介绍兽医学中ETEC感染的最新研究进展和最实际的研究课题。最近,人们开始关注ETEC新毒力因子和新遗传载体的研究。我们还将讨论动物ETEC腹泻的诊断和预防方面的技术。     

Research Advances on Calf Pathogenic Diarrhea and Vaccine

Calf diarrhea is a kind of digestive tract disease caused by a variety of pathogenies, which has a great impact on the survival, growth and development of calves. Escherichia coli, bovine rotavirus, bovine coronavirus and other pathogens often cause diarrhea in calves, in addition, the secondary infection and mixed infection also occurre in different pathogens, which lead to great difficulty for prevention of calf diarrhea. A variety of vaccines have been developed for the prevention and treatment of calf diarrhea at home and abroad. Now, except only minor commercial calf diarrhea vaccines have been found in abroad, there is no one multivalent commercial calf diarrhea vaccine in China. Based on previous study, the progress of pathogens and vaccines for calf diarrhea were elaborated in the study, which could provide exploitation references for the commercial calf diarrhea vaccine in China.     

犊牛病原性腹泻及疫苗研究进展

犊牛腹泻是一种由多种病因引起的消化道疾病,对犊牛的成活、生长、发育等有较大影响,给奶牛和肉牛产业造成巨大经济损失。牛大肠杆菌、轮状病毒、冠状病毒等均可引起犊牛腹泻,且各种病原间还会发生继发感染和混合感染,给防控工作带来较大困难。国内外开发出各种疫苗用于防控犊牛腹泻病,但除了国外有少数商品化疫苗外,目前国内还没有一种针对由多种病原引起的犊牛腹泻病的商品化疫苗。文章就犊牛腹泻病原及疫苗的研究进展进行了阐述,以期为国内开发商品化犊牛腹泻病疫苗提供参考。     

产肠毒素大肠杆菌病商用疫苗的研究进展

产肠毒素大肠杆菌(ETEC)是产房仔猪腹泻的主要细菌性病原,可引起仔猪的黄痢、白痢,给各国养猪业造成较大的经济损失。这也使得很多学者对于如何预防或治疗仔猪黄痢有较深的研究,在我国饲料禁抗的政策下,通过疫苗来预防ETEC引起的黄痢显得尤为重要。文章将展示现阶段,国内外关于该类商用疫苗的研究进展。     

An overview of calf diarrhea - infectious etiology,diagnosis, and intervention

Calf diarrhea is a commonly reported disease in young animals, and still a major cause of productivity and economic loss to cattle producers worldwide. In the report of the 2007 National Animal Health Monitoring System for U.S. dairy, half of the deaths among unweaned calves was attributed to diarrhea. Multiple pathogens are known or postulated to cause or contribute to calf diarrhea development. Other factors including both the environment and management practices influence disease severity or outcomes. The multifactorial nature of calf diarrhea makes this disease hard to control effectively in modern cow-calf operations. The purpose of this review is to provide a better understanding of a) the ecology and pathogenesis of well-known and potential bovine enteric pathogens implicated in calf diarrhea, b) describe diagnostic tests used to detect various enteric pathogens along with their pros and cons, and c) propose improved intervention strategies for treating calf diarrhea.     

Methodology and application of Escherichia coli F4 and F18 encoding infection models in post-weaning pigs

The enterotoxigenic Escherichia coli(ETEC) expressing F4 and F18 fimbriae are the two main pathogens associated with post-weaning diarrhea(PWD) in piglets. The growing global concern regarding antimicrobial resistance(AMR)has encouraged research into the development of nutritional and feeding strategies as well as vaccination protocols in order to counteract the PWD due to ETEC. A valid approach to researching effective strategies is to implement piglet in vivo challenge models with ETEC infection. Thus, the proper application and standardization of ETEC F4 and F18 challenge models represent an urgent priority. The current review provides an overview regarding the current piglet ETEC F4 and F18 challenge models; it highlights the key points for setting the challenge protocols and the most important indicators which should be included in research studies to verify the effectiveness of the ETEC challenge.Based on the current review, it is recommended that the setting of the model correctly assesses the choice and preconditioning of pigs, and the timing and dosage of the ETEC inoculation. Furthermore, the evaluation of the ETEC challenge response should include both clinical parameters(such as the occurrence of diarrhea,rectal temperature and bacterial fecal shedding) and biomarkers for the specific expression of ETEC F4/F18(such as antibody production, specific F4/F18 immunoglobulins(Igs), ETEC F4/F18 fecal enumeration and analysis of the F4/F18 receptors expression in the intestinal brush borders). On the basis of the review, the piglets' response upon F4 or F18 inoculation differed in terms of the timing and intensity of the diarrhea development, on ETEC fecal shedding and in the piglets' immunological antibody response. This information was considered to be relevant to correctly define the experimental protocol, the data recording and the sample collections. Appropriate challenge settings and evaluation of the response parameters will allow future research studies to comply with the replacement, reduction and refinement(3 R) approach, and to be able to evaluate the efficiency of a given feeding, nutritional or vaccination intervention in order to combat ETEC infection.     

Enterotoxigenic K99+ Escherichia coli attachment to host cell receptors inhibited by recombinant pili protein

Most enterotoxigenic Escherichia coli (ETEC) isolated from neonatal cattle with diarrhea (enteric colibacillosis) exhibit the colonization factor antigen, K99. The K99 pili are necessary for the bacteria to bind to a receptor, N-glycolylneuraminic acid-GM3 on the host cells in the small intestine where the bacteria multiply and secrete toxins that cause the diarrhea. When the attachment of the ETEC to host cell is inhibited, the bacteria do not accumulate sufficiently in the gut to cause disease. Since purified K99 pili block K99+ ETEC from binding to host epithelia, three recombinant K99 proteins of different sizes were developed and produced to demonstrate inhibition with in vitro competitive binding assays. The full-length recombinant protein, rK99-476 inhibited the binding of ETEC with an activity similar to that of the native purified K99, whereas the truncated recombinant K99 protein had no inhibitory activity. Thus this binding activity of rK99-476, which is specific and effective in blocking the receptors on the host cells, may be able to competitively inhibit K99+ ETEC infections in cattle.     

Protection against enteric colibacillosis in pigs suckling orally vaccinated dams: evidence for pili as protective antigens

Pregnant gilts were vaccinated orally with Escherichia coli that produced pilus antigens K99 or 987P. The vaccines were live or dead enterotoxigenic E coli (ETEC) or a liver rough non-ETEC strain which has little ability to colonize pig intestine. Pigs born to the gilts were challenge exposed orally with K99+ or 987P+ ETEC, which did not produce heat-labile enterotoxin or flagella and which produced somatic and capsular antigens different from those of the vaccine strains. Control gilts had low titers of serum and colostral antibodies against pilus antigens, and their suckling pigs frequently had fatal diarrhea after challenge exposure. Serum antibody titers against pilus antigens of the vaccine strains increased in the gilts after vaccination with liver ETEC, and the colostral antibody titers of these gilts were higher than those of controls. Pigs suckling such vaccinated gilts were more resistant than controls to challenge strains were of different pilus types, and it could not be attributed to enterotoxin neutralization by colostrum. In contrast to the live ETEC vaccines given to the pregnant gilts, the liver rough non-ETEC and dead ETEC vaccines stimulated little or no production of antibody against pilu, and the pigs born of these vaccinated gilts remained highly susceptible to challenge exposure. The results support the hypothesis that pilu can be protective antigens in oral ETEC vaccines. It was indicated that in the system reported, protection depended on living bacteria for the production of pilus antigens in vivo or for the transport of pilus antigens across intestinal epithelium.     

轮状病毒分子生物学研究进展

轮状病毒(rotavirus,RV)是引起婴幼儿和多种幼龄动物非细菌性腹泻病的主要病原之一,全世界每年因该病所引起人和动物死亡数量众多,并造成了巨大的经济损失。因此,世界卫生组织呼吁将RV疫苗的研制列为最优先发展的疫苗项目之一。对RV的分子生物学研究进展进行了综述,旨在为更好地开展轮状病毒相关基因的实验室研究提供基础。