006 DNA疫苗与抗肿瘤免疫

DNA疫苗是近年发展起来的新一代疫苗,能够诱导宿主体内细胞毒T细胞反应和抗体反应.大量实验研究证明,注射抗肿瘤DNA疫苗能获得肿瘤保护性免疫效应,在肿瘤免疫治疗中应用前景看好.本文对DNA疫苗抗肿瘤免疫的机制、影响因素及应用作一综述.     

核酸疫苗与婴幼儿免疫

编码引起保护性免疫反应的抗原基因重组于真核表达载体构建的疫苗，称核酸疫苗。本文对核酸疫苗的免疫机制，影响免疫应答的主要因素及用于婴幼儿免疫的利弊作一简要综述。     

核酸疫苗与婴幼儿免疫

编码引起保护性免疫反应的抗原基因重组于真核表达载体的构建疫苗，称核酸疫苗。本文对核酸疫苗的免疫机制，影响免疫应答的主要因素及用于婴幼儿免疫的利弊作一简要综述。     

DNA疫苗与抗肿瘤免疫

DNA疫苗是近年发展起来的新一代疫苗 ,能够诱导宿主体内细胞毒T细胞反应和抗体反应。大量实验研究证明 ,注射抗肿瘤DNA疫苗能获得肿瘤保护性免疫效应 ,在肿瘤免疫治疗中应用前景看好。本文对DNA疫苗抗肿瘤免疫的机制、影响因素及应用作一综述     

DNA疫苗与抗肿瘤免疫

DNA疫苗是近年发展起来的新一代疫苗，能够诱导宿主体内细胞毒T细胞反应和抗体反应。本量实验研究证明，注射抗肿瘤DNA疫苗能获得肿瘤保护性免疫效应，在肿瘤免疫治疗中应用前景看好。本文对DNA疫苗抗肿瘤免疫的机制，影响因素及应用作一综述。     

结核病治疗性疫苗的研究进展

耐药结核分枝杆菌的出现以及由于免疫功能失衡导致的免疫耐受是阻碍结核病有效治疗的两个重要原因.治疗性疫苗能通过对已感染结核分枝杆菌的机体产生二次免疫激发,打破机体的免疫耐受,诱导保护性免疫应答而达到清除结核分枝杆菌的目的.目前,结核病治疗性疫苗研究主要集中在DNA疫苗、亚单位疫苗、减毒活疫苗和死疫苗上.因其可纠正机体失衡的免疫状态,且对耐药性的结核分枝杆菌可产生同样的清除作用,所以,近年来结核病治疗性疫苗逐渐受到人们的关注和重视并取得了较大发展.     

结核病治疗性疫苗的研究进展

耐药结核分枝杆菌的出现以及由于免疫功能失衡导致的免疫耐受是阻碍结核病有效治疗的两个重要原因.治疗性疫苗能通过对已感染结核分枝杆菌的机体产生二次免疫激发,打破机体的免疫耐受,诱导保护性免疫应答而达到清除结核分枝杆菌的目的.目前,结核病治疗性疫苗研究主要集中在DNA疫苗、亚单位疫苗、减毒活疫苗和死疫苗上.因其可纠正机体失衡的免疫状态,且对耐药性的结核分枝杆菌可产生同样的清除作用,所以,近年来结核病治疗性疫苗逐渐受到人们的关注和重视并取得了较大发展.     

T细胞表位疫苗的种类及其生物学意义

:T细胞表位疫苗是利用T细胞表位所研制的疫苗 ,它可以诱导机体产生抗病原体的保护性免疫应答 ,人们对T细胞免疫功能及其所识别的抗原性表位有足够的认识后 ,T细胞表位疫苗得以发展起来 ,并且这些疫苗在抗自身免疫紊乱、抗癌以及抗感染等治疗均起到了一定的作用。     

呼吸道合胞病毒病原学和疫苗研究现状

呼吸道合胞病毒（ＲＳＶ）可分为Ａ、Ｂ两亚型，其结构蛋白中，Ｆ蛋白与Ｇ蛋白与诱发保护性免疫应答有关，灭活ＲＳＶ疫苗接种无保护作用，减毒活性疫苗和亚单位疫苗可作为候选疫苗。     

087 T细胞表位疫苗的种类及其生物学意义

Ｔ细胞表位疫苗是利用Ｔ细胞表位所研制的疫苗是它可以诱导机体产生抗病原体的保护性免疫应答，人们对Ｔ细胞免疫功能及其所识别的抗原性表位有足够的认识后，Ｔ细胞表位疫苗得以发展起来，并且这些疫苗在抗自身免疫紊乱、抗癌以及抗感染等治疗均起到一定的作用。     

Helicobacter pylori vaccine strategies--triggering a gut reaction

Helicobacter pylori causes peptic ulcer disease and some forms of gastric cancer; it is one of the most common chronic bacterial infections of humans. Although several prototype protein-based vaccines have shown promising results, they have not cleared infection and/or prevented reinfection. Nucleic acid vaccination offers a useful alternative to protein immunization, especially now that two complete H. pylori genome sequences are available, and facilitates the selection of antigenic targets.     

Successful immunization against gastric infection with Helicobacter species: use of a cholera toxin B-subunit-whole-cell vaccine.

In previous studies we found that immunizing mice with a sonicate of Helicobacter felis and adjuvant cholera toxin (CT; 10 micrograms) protected the animals against challenge with viable H. felis. The aim of this study was to determine whether a low dose of CT or its nontoxic B subunit (CTB) was effective as an adjuvant in Helicobacter oral vaccines. Significant protection against viable H. felis challenge was achieved in the animals immunized with H. felis antigen plus the combination of 0.5 microgram of CT and 10 micrograms of CTB (96%), with H. felis antigen plus 0.5 microgram of CT (95%), and with H. felis antigen plus 10 micrograms of CTB (83%). No protective effect was found in the mice immunized with either H. felis antigen alone or adjuvant CTB and CT alone. Twenty-six percent of mice immunized with Helicobacter pylori antigen plus CT (10 micrograms) were protected against H. felis challenge, confirming the value of the model in predicting effects of immunization in humans. The observation that immunity can be induced with a nontoxic adjuvant CTB opens the way for human studies with H. pylori vaccines and is a further step along the road to effective strategies of prevention of gastroduodenal diseases of major world significance.     

Protection of BALB/c mice against experimental Helicobacter pylori infection by oral immunisation with H pylori heparan sulphate-binding proteins coupled to cholera toxin beta-subunit

The presence of Helicobacter pylori in the gastroduodenal mucosae is associated with chronic active gastritis, peptic ulcers and gastric cancers such as adenocarcinoma and low-grade gastric B-cell lymphoma. In response to the presence of antibiotic-resistant strains, the use of vaccines to combat this infection has become an attractive alternative. The present study used a murine model of infection by a mouse-adapted H. pylori strain to determine whether infection in BALB/c mice can be successfully eradicated by intragastric vaccination with H. pylori heparan sulphate-binding proteins (HSBP) covalently coupled to the beta-subunit of cholera toxin (CTB). It was shown that vaccination confers protection against exposure of BALB/c mice to the pathogen, as revealed by microbiological, histopathological and molecular methods.     

Helicobacter pylori cytotoxin: importance of native conformation for induction of neutralizing antibodies.

We have attempted to express the Helicobacter pylori vacuolating cytotoxin in Escherichia coli. Although the 95-kDa VacA polypeptide was expressed abundantly, it completely lacked any biological activity. In addition, this material failed to induce neutralizing antibodies after immunization of rabbits. In contrast, highly purified high-molecular-mass cytotoxin from the supernatant of H. pylori cultures was active in a HeLa cell assay and effectively induced a neutralizing response in rabbits. Neutralizing sera were shown to contain a high proportion of antibodies which recognized conformational epitopes found only on the native toxin. The data indicate that toxin-neutralizing epitopes are conformational and that potential vaccines based on the cytotoxin may benefit from the use of the intact molecule.     

Immunocytochemical Study of Helicobacter Pylori in the Mucosae of the Gastric Antrum and Rectum

We present the results of bacterioscopic and immunocytochemical study of Helicobacter pylori in biopsy specimens from the gastric antrum and smears from the rectum. Predominance of spiral-shaped vegetative form of Helicobacter pylori in the antrum and the presence of cocci with Helicobacter pylori antigens in smears from the rectum were demonstrated in patients infected with Helicobacter pylori. The diagnostic sensitivity of non-invasive immunocytochemical Helicobacter pylori test in rectal smears was 90%, specificity 76%, and efficiency of the test 84%.     

CD4+CD25+调节性T细胞和TLRs在幽门螺杆菌 免疫逃逸中的作用

宿主感染幽门螺杆菌(H.pylori)后,会产生炎症反应和免疫反应,但宿主不能完全清除H.pylori,原因之一为H.pylori可逃逸宿主免疫形成持续慢性感染。H.pylori免疫逃逸机制尚不明确,目前此机制研究热点为CD4+CD25+调节性T细胞和TLRs在H.pylori免疫逃逸中的作用。     

Immunological and molecular characterization of Helicobacter felis urease.

Urease activity has recently been shown to be an important virulence determinant for Helicobacter pylori, allowing it to survive the low pH of the stomach during colonization. Experimental murine infection with Helicobacter felis is now being used as a model for H. pylori infection to study the effects of vaccines, antibiotics, and urease inhibitors on colonization. However, little information comparing the ureases of H. felis and H. pylori is available. Urease was partially purified from the cell surface of H. felis ATCC 49179 by A-5M agarose chromatography, resulting in an eightfold increase in specific activity over that of crude urease. The apparent Km for urea for the partially purified urease was 0.4 mM, and the enzyme was inhibited in a competitive manner by flurofamide (50% inhibitory concentration = 0.12 microM). Antiserum to whole cells of H. pylori recognized both H. pylori and H. felis urease B subunits. Antiserum raised against H. felis whole cells recognized the large and small autologous urease subunits and the cpn60 heat shock molecule in both H. felis and H. pylori. However, this antiserum showed only a weak reaction with the B subunit of H. pylori urease. Two oligomeric DNA sequences were used as probes to evaluate the relatedness of H. felis and H. pylori urease gene sequences. One 30-mer from the ureA sequence, which had been shown previously to be specific for H. pylori, failed to hybridize to H. felis genomic DNA. A probe to the putative coding sequence for the active site of the H. pylori ureB subunit hybridized at low intensity to a 2.8-kb fragment of BamHI-HindIII-digested H. felis DNA, suggesting that the sequences were homologous but not identical, a result confirmed from the recently published sequences of ureA and ureB from H. felis.     

Therapeutic intragastric vaccination against Helicobacter pylori in mice eradicates an otherwise chronic infection and confers protection against reinfection.

Chronic infection of the gastroduodenal mucosae by the gram-negative spiral bacterium Helicobacter pylori is responsible for chronic active gastritis, peptic ulcers, and gastric cancers such as adenocarcinoma and low-grade gastric B-cell lymphoma. The success of eradication by antibiotic therapy is being rapidly hampered by the increasing occurrence of antibiotic-resistant strains. An attractive alternative approach to combat this infection is represented by the therapeutic use of vaccines. In the present work, we have exploited the mouse model of persistent infection by mouse-adapted H. pylori strains that we have developed to assess the feasibility of the therapeutic use of vaccines against infection. We report that an otherwise chronic H. pylori infection in mice can be successfully eradicated by intragastric vaccination with H. pylori antigens such as recombinant VacA and CagA, which were administered together with a genetically detoxified mutant of the heat-labile enterotoxin of Escherichia coli (referred to as LTK63), in which the serine in position 63 was replaced by a lysine. Moreover, we show that therapeutic vaccination confers efficacious protection against reinfection. These results represent strong evidence of the feasibility of therapeutic use of VacA- or CagA-based vaccine formulations against H. pylori infection in an animal model and give substantial preclinical support to the application of this kind of approach in human clinical trials.     

初探幽门螺杆菌感染与反流性食管炎的相关性

目的探究反流性食管炎与幽门螺杆菌感染二者的相关性进行。方法选取1 000例反流性食管炎患者,均采用快速尿素酶试验对幽门螺杆菌的感染情况进行检查。按Tygatat分级标准进行分级,对不同级别的反流性食管炎患者感染幽门螺杆菌的发生率及程度进行比较。结果 59%的患者感染了反流性食管炎的幽门螺杆菌,其中Ⅰ级反流性食管炎感染幽门螺杆菌的发生率是66.95%,Ⅱ级感染的发生率是65.83%,Ⅲ级感染的发生率是53.75%,Ⅳ级感染的发生率是45.71%,Ⅴ级感染的发生率是33.33%。由此可见,随着患者反流性食管炎的病情不断加重,幽门螺杆菌感染的发生率呈下降趋势。反之,患者感染的发生率增加。结论反流性食管炎严重程度与幽门螺杆菌感染的发生率呈反比例关系,幽门螺杆菌对反流性食管炎在一定程度上起到了保护的效果,这是根除幽门螺杆菌最佳时机,可降低对反流性食管炎的影响。