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口服表达禽流感病毒血凝素的重组乳球菌诱导黏膜和系统免疫应答。

Oral immunization with recombinant Lactococcus lactis expressing the hemagglutinin of the avian influenza virus induces mucosal and systemic immune responses.

机构信息

Key Lab of Animal Physiology & Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu 210095, China.

出版信息

Future Microbiol. 2012 Aug;7(8):1003-10. doi: 10.2217/fmb.12.69.

DOI:10.2217/fmb.12.69
PMID:22913358
Abstract

AIMS

The aim of the study in this article is to explore a safe, convenient and effective oral mucosal vaccine candidate against highly pathogenic avian influenza.

MATERIALS & METHODS: We have constructed an oral mucosal vaccine, LL36EH, by use of the genetically stable θ-replicating vector pMG36E, which expressed the fusion protein hemagglutinin 1 (HA(1)) in a live carrier, Lactococcus lactis MG1363. LL36EH was administered orally to mice three times at 2-week intervals. The specific serum IgG and mucosal IgA antibodies were detected and evaluated at different time points after immunization.

RESULTS

The results showed that LL36EH could significantly induce specific anti-HA(1) IgA antibody in the intestine and specific anti-HA(1) IgG antibody in the serum (p < 0.05). Additionally, when the splenic lymphocytes isolated from immunized mice were stimulated by HA(1) antigen in vitro, splenic lymphocyte proliferative reaction and secretions of the cytokines IFN-γ and IL-4 were also significantly increased. Most importantly, the mice that were immunized with LL36EH were protected to some extent against lethal challenge of the H5N1 virus.

CONCLUSION

LL36EH triggered the anti-HA(1)-specific humoral and cellular immune responses and protective immunity. Therefore, oral immunization with LL36EH could be a valuable strategy against highly pathogenic avian influenza for humans and animals.

摘要

目的

本文研究的目的是探索一种安全、方便、有效的针对高致病性禽流感的口腔黏膜疫苗候选物。

材料与方法

我们构建了一种口腔黏膜疫苗 LL36EH,该疫苗利用遗传稳定的θ复制载体 pMG36E,在活载体乳球菌 lactis MG1363 中表达融合蛋白血凝素 1(HA(1))。LL36EH 在 2 周的间隔时间内通过口服给予小鼠 3 次。在免疫后不同时间点检测和评估特异性血清 IgG 和黏膜 IgA 抗体。

结果

结果表明,LL36EH 能显著诱导肠道中特异性抗 HA(1) IgA 抗体和血清中特异性抗 HA(1) IgG 抗体(p < 0.05)。此外,当从免疫小鼠分离的脾淋巴细胞受到 HA(1)抗原体外刺激时,脾淋巴细胞增殖反应和细胞因子 IFN-γ 和 IL-4 的分泌也显著增加。最重要的是,用 LL36EH 免疫的小鼠在一定程度上免受 H5N1 病毒的致死性攻击。

结论

LL36EH 引发了针对 HA(1)的特异性体液和细胞免疫反应和保护免疫。因此,口服免疫 LL36EH 可能是针对人类和动物高致病性禽流感的一种有价值的策略。

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