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两种表达口蹄疫病毒VP1抗原与猪粒细胞巨噬细胞集落刺激因子融合蛋白的重组腺病毒的免疫应答

Immune responses of two recombinant adenoviruses expressing VP1 antigens of FMDV fused with porcine granulocyte macrophage colony-stimulating factor.

作者信息

Du Yijun, Jiang Ping, Li Yufeng, He Hairong, Jiang Wenming, Wang Xinglong, Hong Weibin

机构信息

Key Laboratory of Animal Diseases Diagnostic and Immunology, College of Veterinary Medicine, Nanjing Agricultural University, Ministry of Agriculture, Nanjing 210095, China.

出版信息

Vaccine. 2007 Nov 28;25(49):8209-19. doi: 10.1016/j.vaccine.2007.09.062. Epub 2007 Oct 15.

Abstract

Foot-and-mouth disease (FMD) is a highly contagious and economically devastating vesicular disease of cloven-hoofed animals. In the present report, we constructed and characterized the immune responses conferred by two recombinant adenoviruses expressing VP1 epitopes (three amino acid residues 21-60, 141-160 and 200-213 in VP1, designated VPe) or VP1 protein of FMDV fused with porcine granulocyte macrophage colony-stimulating factor (named rAd-GMCSF-VPe and rAd-GMCSF-VP1). Seven groups of female BALB/c mice each containing 18 mice were inoculated subcutaneously twice at 2-week intervals with the recombinant adenoviruses. Then the protective efficacy of the two adenoviruses was detected in guinea pigs and swine. The results showed that the highest levels of FMDV-specific T cell proliferation, IFN-gamma and IL-4 could be induced by rAd-GMCSF-VPe expressing fusion GMCSF-VPe, and the highest level of FMDV-specific humoral immune responses could be induced by rAd-GMCSF-VP1 expressing fusion GMCSF-VP1 in mice. All guinea pigs and swine co-administrated with rAd-GMCSF-VPe and rAd-GMCSF-VP1 were protected from viral challenge, even though the neutralizing antibody titers were significantly lower than those in the group inoculated with inactivated FMD vaccine. It demonstrated that co-administration of rAd-GMCSF-VPe and rAd-GMCSF-VP1 might be attractive candidate vaccines for preventing FMDV infection.

摘要

口蹄疫(FMD)是一种偶蹄动物的高度传染性且具有经济毁灭性的水疱病。在本报告中,我们构建并表征了两种表达VP1表位(VP1中三个氨基酸残基21 - 60、141 - 160和200 - 213,命名为VPe)或与猪粒细胞巨噬细胞集落刺激因子融合的口蹄疫病毒VP1蛋白(命名为rAd - GMCSF - VPe和rAd - GMCSF - VP1)的重组腺病毒所赋予的免疫反应。将七组每组18只雌性BALB/c小鼠每隔2周皮下接种两次重组腺病毒。然后在豚鼠和猪中检测这两种腺病毒的保护效力。结果表明,表达融合GMCSF - VPe的rAd - GMCSF - VPe可诱导最高水平的口蹄疫病毒特异性T细胞增殖、IFN - γ和IL - 4,而表达融合GMCSF - VP1的rAd - GMCSF - VP1在小鼠中可诱导最高水平的口蹄疫病毒特异性体液免疫反应。所有同时接种rAd - GMCSF - VPe和rAd - GMCSF - VP1的豚鼠和猪都受到了病毒攻击的保护,尽管中和抗体滴度显著低于接种灭活口蹄疫疫苗的组。这表明同时接种rAd - GMCSF - VPe和rAd - GMCSF - VP1可能是预防口蹄疫病毒感染的有吸引力的候选疫苗。

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