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表达猪蛔虫候选疫苗抗原(As16)与霍乱毒素B亚基融合蛋白的转基因水稻植株在小鼠体内的口服免疫原性及保护效力

Oral immunogenicity and protective efficacy in mice of transgenic rice plants producing a vaccine candidate antigen (As16) of Ascaris suum fused with cholera toxin B subunit.

作者信息

Matsumoto Yasunobu, Suzuki Seiko, Nozoye Tomoko, Yamakawa Takashi, Takashima Yasuhiro, Arakawa Takeshi, Tsuji Naotoshi, Takaiwa Fumio, Hayashi Yoshihiro

机构信息

Laboratory of Global Animal Resource Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.

出版信息

Transgenic Res. 2009 Apr;18(2):185-92. doi: 10.1007/s11248-008-9205-4. Epub 2008 Sep 2.

DOI:10.1007/s11248-008-9205-4
PMID:18763047
Abstract

Cereal crops such as maize and rice are considered attractive for vaccine production and oral delivery. Here, we evaluated the rice Oryza sativa for production of As16-an antigen protective against the roundworm Ascaris suum. The antigen was produced as a chimeric protein fused with cholera toxin B subunit (CTB), and its expression level in the endosperm reached 50 microg/g seed. Feeding the transgenic (Tg) rice seeds to mice elicited an As16-specific serum antibody response when administered in combination with cholera toxin (CT) as the mucosal adjuvant. Although omitting the adjuvant from the vaccine formulation resulted in failure to develop the specific immune response, subcutaneous booster immunization with bacterially expressed As16 induced the antibody response, indicating priming capability of the Tg rice. Tg rice/CT-fed mice orally administered A. suum eggs had a lower lung worm burden than control mice. This suggests that the rice-delivered antigen functions as a prophylactic edible vaccine for controlling parasitic infection in animals.

摘要

玉米和水稻等谷类作物被认为是生产疫苗和口服给药的理想选择。在此,我们评估了水稻(Oryza sativa)用于生产As16的能力,As16是一种针对猪蛔虫(Ascaris suum)具有保护作用的抗原。该抗原作为与霍乱毒素B亚基(CTB)融合的嵌合蛋白进行表达,其在内胚乳中的表达水平达到50微克/克种子。将转基因(Tg)水稻种子与霍乱毒素(CT)作为黏膜佐剂联合喂给小鼠后,可引发As16特异性血清抗体反应。尽管疫苗配方中省略佐剂会导致无法产生特异性免疫反应,但用细菌表达的As16进行皮下加强免疫可诱导抗体反应,这表明Tg水稻具有启动免疫的能力。口服感染猪蛔虫卵的Tg水稻/CT喂养小鼠的肺部寄生虫负担低于对照小鼠。这表明水稻递送的抗原可作为预防性可食用疫苗,用于控制动物的寄生虫感染。

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