Development of DNA Vaccines and Oral Vaccines against Helicobacter pylori Infection

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Project title

Code/計畫編號

NSC98-2313-B019-007-MY3

Translated Name/計畫中文名

抗幽門螺旋桿菌(Helicobacter pylori)感染之DNA疫苗及口服疫苗之研發

Project Coordinator/計畫主持人

Chang-Jer Wu

Funding Organization/主管機關

National Science and Technology Council

Department/Unit

Department of Food Science

Website

https://www.grb.gov.tw/search/planDetail?id=1870475

Year

2009

Start date/計畫起

01-08-2009

Expected Completion/計畫迄

31-07-2010

Bugetid/研究經費

1000千元

ResearchField/研究領域

食品科技(農)
生物技術(醫)
藥學

"研究指出幽門螺旋桿菌感染和人類腸胃道疾病有相當的關聯性，目前認為其可引起的消化道疾病，包括慢性胃炎、胃潰瘍、十二指腸潰瘍、胃腺癌等疾病。人類幽門螺旋桿菌感染率甚高，全世界約有50%以上的成年人曾遭受感染。目前治療幽門螺旋桿菌的感染，主是採用抗生素合併其他藥物治療。然而，臨床上仍發現患者有復發的現象發生，藥物治療幽門螺旋桿菌感染的失敗原因，是以幽門螺旋桿菌對藥物產生抗藥性最具關鍵性，為了克服以上問題，急需要發展出有效的抗幽門螺旋桿菌疫苗來達到預防的目的。因為發展幽門螺旋桿菌疫苗及研究其感染之機轉，都需要一個合適及方便的小鼠感染模式，目前我們實驗室已成功地建立了幽門螺旋桿菌感染C3H/HeN 小鼠的動物模式，並可在小鼠腸胃道偵測到幽門螺旋桿菌的菌落及其所誘發的發炎現象。因此在本研究計劃中，我們將利用此幽門螺旋桿菌感染C3H/HeN 小鼠動物模式，來研究及開發DNA 疫苗及三種型式的口服疫苗[減毒之鼠傷寒沙門氏菌、幾丁聚醣、卵黃免疫球蛋白(IgY)]對於幽門螺旋桿菌感染之預防及治療的效果。幽門螺旋桿菌能分泌尿素酶，將尿素轉變成二氧化碳及氨中和胃酸，使其得以在胃中存活，是一個很好的疫苗抗原選擇。所以，我們首先將幽門螺旋桿菌尿素酶B 次單位基因構築於原核生物表現載體(pET-30a 及pUC19) 及真核生物表現載體(pCJ-3)中，產生不同的DNA 疫苗。然後，再以肌肉注射，或以減毒之鼠傷寒沙門氏菌、幾丁聚醣做為口服疫苗載體，或利用雞隻免疫後所產生含有抗幽門螺旋桿菌的IgY 抗體的被動免疫方式，分別免疫小鼠，來比較DNA 疫苗及三種口服疫苗所誘發的預防或治療之效果及其免疫機轉。第三，我們將嘗試找出利用DNA 疫苗及口服疫苗免疫小鼠的最佳組合方式。第四，我們將嘗試以不同的佐劑，增加DNA 疫苗及口服疫苗的效果，以期產生更好的免疫保護力。經由上述的研究，我們希望能證明抗幽門螺旋桿菌DNA 疫苗或口服疫苗能確實對於幽門螺旋桿菌感染產生有效地預防及治療的效果。並且在小鼠動物模式上發展出方便及有效的抗幽門螺旋桿菌DNA 疫苗或口服疫苗，為未來的人體臨床實驗提供必要的實驗資料。" "Helicobacter pylori (H. pylori), which has been associated with gastritis and duodenal ulears, commonly chronically infects adults. It is infected in approximately half of the world’s population. The common treatment of H. pylori infection includes antibiotics and a combination of a proton pump inhibitor. However, there are several problems with these therapies, such as side effects related to the use of a high dose of antibiotics and the emergence of resistant strains of H. pylori. Therefore, the development of a prophylactic vaccine may be an attractive strategy against H. pylori infection. The H. pylori infected animal model is needed to investigate the pathogenesis of H. pylori and development of the anti-H. pylori vaccines. Our preliminary results show that H. pylori can successfully infect C3H/HeN mice, and the inflammatory cytokines can also be detected in the gastrointestinal tract. In this proposed grant, we will investigate the capacity of DNA vaccine and three kinds of oral vaccines, live attenuated Salmonella based, chitosan based and immunoglobulin Y (IgY) based, to induce the protective immunity and control of H. pylori infection. The urease protein is the most accepted and potential vaccine candidate of the many investigated antigens of H. pylori. First, we will clone H. pylori urease B gene into the prokaryotic and eukaryotic expression vector, pET-30a pUC19 and pCJ-3, to generate the H. pylori DNA vaccine, respectively. Then, we will investigate the preventive or therapeutic effects and immune mechanisms induced by the H. pylori DNA vaccine and three kinds of oral vaccines on the H. pylori infected C3H/HeN mice model. Third, the conditions of DNA vaccine and oral vaccines will be optimized to achieve better immunization in mouse. Fourth, we will test the efficacy of the H. pylori DNA vaccine and oral vaccines with adjuvant. These results will demonstrate that the development of appropriate vaccination can set the stage for preventing and control of H. pylori infection. Through all these efforts, we hope to develop an effective anti-H. pylori DNA vaccine or oral vaccine in the mouse model and prepare the preclinical data for a future human clinical trial."

Keyword(s)

幽門螺旋桿菌
C3H/HeN 品系小鼠
DNA 疫苗
口服疫苗
減毒之鼠傷寒沙門氏菌
幾丁聚醣
卵黃免疫球蛋白
Helicobacter pylori
C3H/HeN mice
DNA vaccine
oral vaccine
attenuated Salmonella
chitosan
Immunoglobulin Y

DSpace CRIS

Development of DNA Vaccines and Oral Vaccines against Helicobacter pylori Infection

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