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肺内递送CpG-寡脱氧核苷酸微滴可为新生肉鸡提供抗大肠杆菌败血症的保护。

Intrapulmonary Delivery of CpG-ODN Microdroplets Provides Protection Against Escherichia coli Septicemia in Neonatal Broiler Chickens.

作者信息

Goonewardene Kalhari Bandara, Popowich Shelly, Gunawardana Thushari, Gupta Ashish, Kurukulasuriya Shanika, Karunarathna Ruwani, Chow-Lockerbie Betty, Ahmed Khawaja Ashfaque, Tikoo Suresh K, Foldvari Marianna, Willson Philip, Gomis Susantha

机构信息

A Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, S7N 5B4, Canada.

B Vaccine and Infectious Disease Organization, 120 Veterinary Road, University of Saskatchewan, Saskatoon, SK, S7N 5E3, Canada.

出版信息

Avian Dis. 2017 Dec;61(4):503-511. doi: 10.1637/11684-060617-Reg.1.

Abstract

Synthetic oligodeoxynucleotides (ODN) containing unmethylated cytosine phosphodiester guanine (CpG) motifs (CpG-ODN) are effective immunostimulatory agents against a variety of viral, bacterial, and protozoan diseases in different animals including poultry. We have recently demonstrated that in ovo injection of CpG-ODN confers protection in neonatal chickens against bacterial septicemias. The objective of this study was to investigate the effectiveness of needle-free intrapulmonary (IPL) delivery of CpG-ODN microdroplets against Escherichia coli infection in neonatal chicks. In the present study, we used 880 chicks in total keeping 40 chicks per group. Chicks were delivered CpG-ODN or saline by IPL at the day 1 of hatch. Three days later, chicks were challenged with two doses (1 × 10 CFU, n = 20 or 1 × 10 CFU, n = 20) of E. coli. Chicks treated with CpG-ODN by the IPL route had significantly lower clinical signs and bacterial load compared to the group treated with saline ( P < 0.05). CpG-ODN-treated groups were significantly protected against E. coli septicemia. We observed dose- and exposure time-dependent immunoprotective effects of IPL CpG-ODN in chicks. We found that IPL delivery of CpG-ODN can induce protective immunity as early as 6 hr that remains effective at least until day 5 post-treatment. Moreover, there were no adverse effects of IPL delivery of CpG-ODN on growth or mortality up to 42 days of age. Based on these findings, it can be suggested that CpG-ODN delivery by IPL route can be a promising alternative to antibiotics for inducing protective immunity in chicks during the critical first week of neonatal life.

摘要

含有未甲基化胞嘧啶磷酸二酯鸟嘌呤(CpG)基序的合成寡脱氧核苷酸(ODN)(CpG-ODN)是针对包括家禽在内的不同动物的多种病毒、细菌和原生动物疾病的有效免疫刺激剂。我们最近证明,在鸡胚中注射CpG-ODN可使新生雏鸡免受细菌败血症的侵害。本研究的目的是调查通过无针肺内(IPL)递送CpG-ODN微滴对新生雏鸡大肠杆菌感染的有效性。在本研究中,我们总共使用了880只雏鸡,每组40只。在雏鸡孵化第1天通过IPL给它们递送CpG-ODN或生理盐水。三天后,用两剂(1×10CFU,n = 20或1×10CFU,n = 20)大肠杆菌对雏鸡进行攻毒。与用生理盐水处理的组相比,通过IPL途径用CpG-ODN处理的雏鸡的临床症状和细菌载量明显更低(P < 0.05)。用CpG-ODN处理的组对大肠杆菌败血症有明显的保护作用。我们观察到IPL CpG-ODN在雏鸡中具有剂量和暴露时间依赖性的免疫保护作用。我们发现,IPL递送CpG-ODN最早可在6小时诱导保护性免疫,至少在治疗后第5天仍然有效。此外,直到42日龄,IPL递送CpG-ODN对生长或死亡率均无不良影响。基于这些发现,可以认为通过IPL途径递送CpG-ODN可能是在新生生命关键的第一周诱导雏鸡保护性免疫的一种有前途的抗生素替代品。

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