本文關(guān)鍵詞：動(dòng)物特異性CpG ODN的設(shè)計(jì)、篩選及對(duì)疫苗的增效作用　出處：《吉林大學(xué)》2010年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： CpG ODN 種屬特異性 口蹄疫 狂犬病 佐劑

【摘要】： CpG ODN是含有非甲基化胞嘧啶—鳥(niǎo)嘌呤二核苷酸的單鏈脫氧寡核苷酸,通過(guò)與TLR9結(jié)合,能刺激人及哺乳動(dòng)物的天然免疫系統(tǒng),誘導(dǎo)產(chǎn)生以Th1型為主的免疫應(yīng)答。CpG ODN作為人用疫苗佐劑在臨床實(shí)驗(yàn)中取得了可喜的成果,作為動(dòng)物疫苗佐劑的研究較少,這是因?yàn)镃pG ODN具有種屬特異性,即對(duì)一種動(dòng)物表現(xiàn)生物活性的CpG ODN,在另一種動(dòng)物則未必表現(xiàn)出同樣的或同樣強(qiáng)度的生物學(xué)活性。實(shí)驗(yàn)證明以CpG為核心的六核苷酸即CpG基序是導(dǎo)致種屬特異性的原因。 為了獲得對(duì)牛或犬有免疫刺激作用的CpG ODN,以作為動(dòng)物疫苗新型佐劑,我們根據(jù)CpG基序設(shè)計(jì)了60多條含有各種CpG基序的CpG ODN,經(jīng)過(guò)體外篩選,獲得了對(duì)犬免疫細(xì)胞有刺激活性的YW07、YW08和YW09；將YW07與含有鋁佐劑的狂犬滅活疫苗聯(lián)用免疫小鼠及犬,YW07能顯著提高抗體產(chǎn)生水平及持續(xù)時(shí)間,并偏向Th1型免疫應(yīng)答,且完全保護(hù)小鼠抵抗狂犬病毒的攻擊。 同時(shí),獲得了對(duì)牛免疫細(xì)胞有刺激活性的RW12,將RW12與含有206油佐劑的口蹄疫重組蛋白A7疫苗聯(lián)用免疫小鼠及牛,RW12能顯著提高其在動(dòng)物體內(nèi)的抗體水平及持續(xù)時(shí)間,一次免疫84天后進(jìn)行攻毒實(shí)驗(yàn),A7+206油+RW12組的牛80%(4／5)得到保護(hù),滅活疫苗組只有50%(2／4)的牛得到保護(hù)。 綜上所述,我們開(kāi)發(fā)的牛、犬特異性CpG ODN有望成為動(dòng)物疫苗的新型高效佐劑。
[Abstract]:CpG ODN is a single stranded oligonucleotides containing unmethylated cytosine guanine dinucleotide -, combined with TLR9, can stimulate the innate immune system of human and other mammals, to induce Th1 type immune response.CpG ODN as vaccine adjuvant yielded promising results in clinical trials, as adjuvants of animal vaccine less this is because, CpG ODN has the species specificity, namely a kind of animal performance of the biological activity of CpG ODN, in another animal may not exhibit the same biological activity or the same strength. Results showed that six nucleotides with CpG as the core CpG motif is the cause of species specificity.
In order to obtain bovine or dog has the immunostimulatory effects of CpG ODN, as a new animal vaccine adjuvant, we designed more than 60 containing CpG motif of CpG ODN according to the CpG motif, after screening in vitro, obtained the stimulating activity of YW07 on canine immune cells, YW08 and YW09; YW07 and containing aluminum adjuvant the inactivated rabies vaccine combined with immune mice and dogs, YW07 could significantly increase the antibody level and duration, and bias of Th1 immune response, and completely protects mice against rabies virus attacks.
At the same time, the bovine immune cells stimulates the activity of RW12, RW12 and containing 206 oil adjuvant FMD recombinant protein A7 vaccine immunized mice and cattle, RW12 can significantly improve the antibody level of animal immunization and duration, 84 days after the poison attack experiment, 80% bovine A7+206 oil the +RW12 group (4 / 5) to be protected, the inactivated vaccine group was only 50% (2 / 4) of the cattle are protected.
In summary, the bovine, dog specific CpG ODN, which we have developed, is expected to be a new and highly efficient adjuvant for animal vaccines.

【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2010
【分類號(hào)】：R392.9

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前1條

1 王靜;特定寡核苷酸對(duì)大鼠實(shí)驗(yàn)性牙移動(dòng)骨改建影響作用的研究[D];吉林大學(xué);2011年

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本文編號(hào)：1385259