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黏膜应用阳离子聚(D,L-丙交酯-共-乙交酯)微球作为 DNA 疫苗载体和佐剂,以保护鸡免受传染性法氏囊病的侵害。

Mucosal application of cationic poly(D,L-lactide-co-glycolide) microparticles as carriers of DNA vaccine and adjuvants to protect chickens against infectious bursal disease.

机构信息

Clinic for Poultry, University of Veterinary Medicine Hannover, Bünteweg 17, 30559 Hannover, Germany.

出版信息

Vaccine. 2013 Aug 12;31(36):3656-62. doi: 10.1016/j.vaccine.2013.06.011. Epub 2013 Jun 15.

Abstract

Infectious bursal disease virus (IBDV) is an immunosuppressive virus of chickens. The virus protein (VP) 2 induces neutralizing antibodies, which protect chickens against the disease. The aim of this study was to develop a cationic poly(d,l-lactide-co-glycolide) (PLGA) microparticle (MP) based IBDV-VP2 DNA vaccine (MP-IBDV-DNA) for chickens to be delivered orally and by eye drop route. The tested IBDV-VP2 DNA vaccines were immunogenic for specific-pathogen-free chickens and induced an antibody response after intramuscular application. Co-inoculation with a plasmid encoding chicken IL-2 (chIL-2) or CpG-ODN did not significantly improve protection against IBDV challenge. However, the application of a MP-IBDV-DNA vaccine alone or in combination with a delayed oral and eye drop application of cationic MP loaded with CpG-ODN or chIL-2 improved protection against challenge. The MP-IBDV-DNA-vaccinated chickens showed less pathological and histopathological bursal lesions, a reduced IBDV antigen load as well as T-cell influx into the bursa of Fabricius (BF) compared to the other groups (p<0.05). The addition of chIL-2 loaded MP improved challenge virus clearance from the BF as demonstrated by lower neutralizing antibody titers and reduced IL-4 and IFN-α mRNA expression in the bursa at 7 days postchallenge compared to the other challenged groups. Overall, the efficacy of the IBDV-DNA vaccine was improved by adsorption of the DNA vaccine onto cationic PLGA-MP, which also allowed mucosal application of the DNA vaccine.

摘要

传染性法氏囊病病毒(IBDV)是一种鸡的免疫抑制性病毒。该病毒的蛋白(VP)2 诱导中和抗体,从而保护鸡免受该疾病的侵害。本研究旨在开发一种阳离子聚(D,L-丙交酯-共-乙交酯)(PLGA)微球(MP)基于 IBDV-VP2 DNA 疫苗(MP-IBDV-DNA),通过口服和滴眼途径用于鸡。经测试,该 IBDV-VP2 DNA 疫苗对无特定病原体鸡具有免疫原性,并在肌肉内应用后诱导抗体反应。与编码鸡白细胞介素 2(chIL-2)或 CpG-ODN 的质粒共接种并没有显著提高对 IBDV 攻毒的保护作用。然而,单独应用或与阳离子 MP 负载 CpG-ODN 或 chIL-2 的延迟口服和滴眼应用联合应用 MP-IBDV-DNA 疫苗可提高对攻毒的保护作用。与其他组相比(p<0.05),接种 MP-IBDV-DNA 疫苗的鸡表现出较少的病理性和组织病理学法氏囊病变、降低的 IBDV 抗原负荷以及进入法氏囊的 T 细胞流入。与其他攻毒组相比,负载 chIL-2 的 MP 的添加通过降低攻毒后 7 天法氏囊中的中和抗体滴度和降低 IL-4 和 IFN-α mRNA 表达,改善了对攻毒的病毒清除。总的来说,通过将 DNA 疫苗吸附到阳离子 PLGA-MP 上,提高了 IBDV-DNA 疫苗的功效,同时也允许粘膜应用该 DNA 疫苗。

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