{"title":"利用 \"肠-肺-轴 \"概念,通过肺内注射产气荚膜梭菌活疫苗保护肉鸡免受坏死性肠炎的侵袭","authors":"Hemlata Gautam, Khawaja Ashfaque Ahmed, Iresha Subhasinghe, Shelly Popowich, Ayumi Matsuyama-Kato, Betty Chow-Lockerbie, Lisanework E Ayalew, Suresh Tikoo, Philip Griebel, Susantha Gomis","doi":"10.1637/aviandiseases-D-24-00014","DOIUrl":null,"url":null,"abstract":"<p><p><i>Clostridium perfringens</i> (CP)-induced necrotic enteritis (NE) is an economically important disease in the broiler chicken industry. The incidence of NE is common in 3-to-6-wk-old broiler chickens, once maternal antibodies start declining. Developing an effective vaccination strategy against NE, preferably delivering a single dose of vaccine at hatch to protect broiler chickens against NE without a booster vaccine, is an enormous challenge. The objective of this study was to induce mucosal immunity in the intestines against NE by intrapulmonary (IPL) delivery of a live CP vaccine at hatch, exploiting the gut-lung-axis (GLA) concept by vaccine delivery following <i>in ovo</i> administration of cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG-ODN) to induce immune cell maturation in the lungs. Experiments were conducted to explore the dose of CP and immune protection against heterologous CP challenge, and to study the efficacy of IPL delivery of a CP vaccine without a booster. Additional studies were conducted to measure serum immunoglobulin (Ig)Y, mucosal IgA, and histopathology of lungs following vaccination. Delivery of a live CP vaccine by the IPL route, with or without <i>in ovo</i> CpG-ODN, provided significant protection against NE (<i>P</i> < 0.0001). Systemic IgY and mucosal IgA against CP were correlated with protection against NE. There was no necrosis or inflammation in the pulmonary parenchyma. There was a low number of CP isolated from the lungs following live CP delivery by the IPL route. A significant influx of (<i>P</i> < 0.001) of CD8+ T cells and macrophages were noted in the lungs 2 days following live CP delivery by the IPL route. IPL delivery of a live CP vaccine, rather than inactivated CP, provided better protection. This study demonstrated the utility in exploiting the GLA concept in vaccine delivery in broiler chickens.</p>","PeriodicalId":516846,"journal":{"name":"Avian diseases","volume":"68 3","pages":"240-253"},"PeriodicalIF":0.0000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Protection of Broiler Chickens Against Necrotic Enteritis by Intrapulmonary Delivery of a Live Clostridium perfringens Vaccine Exploiting the Gut-Lung-Axis Concept.\",\"authors\":\"Hemlata Gautam, Khawaja Ashfaque Ahmed, Iresha Subhasinghe, Shelly Popowich, Ayumi Matsuyama-Kato, Betty Chow-Lockerbie, Lisanework E Ayalew, Suresh Tikoo, Philip Griebel, Susantha Gomis\",\"doi\":\"10.1637/aviandiseases-D-24-00014\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><i>Clostridium perfringens</i> (CP)-induced necrotic enteritis (NE) is an economically important disease in the broiler chicken industry. The incidence of NE is common in 3-to-6-wk-old broiler chickens, once maternal antibodies start declining. Developing an effective vaccination strategy against NE, preferably delivering a single dose of vaccine at hatch to protect broiler chickens against NE without a booster vaccine, is an enormous challenge. The objective of this study was to induce mucosal immunity in the intestines against NE by intrapulmonary (IPL) delivery of a live CP vaccine at hatch, exploiting the gut-lung-axis (GLA) concept by vaccine delivery following <i>in ovo</i> administration of cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG-ODN) to induce immune cell maturation in the lungs. Experiments were conducted to explore the dose of CP and immune protection against heterologous CP challenge, and to study the efficacy of IPL delivery of a CP vaccine without a booster. Additional studies were conducted to measure serum immunoglobulin (Ig)Y, mucosal IgA, and histopathology of lungs following vaccination. Delivery of a live CP vaccine by the IPL route, with or without <i>in ovo</i> CpG-ODN, provided significant protection against NE (<i>P</i> < 0.0001). Systemic IgY and mucosal IgA against CP were correlated with protection against NE. There was no necrosis or inflammation in the pulmonary parenchyma. There was a low number of CP isolated from the lungs following live CP delivery by the IPL route. A significant influx of (<i>P</i> < 0.001) of CD8+ T cells and macrophages were noted in the lungs 2 days following live CP delivery by the IPL route. IPL delivery of a live CP vaccine, rather than inactivated CP, provided better protection. This study demonstrated the utility in exploiting the GLA concept in vaccine delivery in broiler chickens.</p>\",\"PeriodicalId\":516846,\"journal\":{\"name\":\"Avian diseases\",\"volume\":\"68 3\",\"pages\":\"240-253\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Avian diseases\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1637/aviandiseases-D-24-00014\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Avian diseases","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1637/aviandiseases-D-24-00014","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
产气荚膜梭菌(CP)诱发的坏死性肠炎(NE)是肉鸡养殖业中的一种重要经济疾病。一旦母源抗体开始下降,3-6 周龄的肉鸡就会经常发生坏死性肠炎。开发一种有效的 NE 疫苗接种策略是一项巨大的挑战,最好是在孵化时接种一剂疫苗,无需加强免疫即可保护肉鸡免受 NE 的感染。本研究的目的是在孵化时通过肺内注射(IPL)CP 活疫苗诱导肠道黏膜对 NE 的免疫,利用肠-肺-轴(GLA)概念,在卵内注射胞嘧啶-硫代磷酸鸟嘌呤寡脱氧核苷酸(CpG-ODN)后注射疫苗,诱导肺部免疫细胞成熟。实验探讨了氯化石蜡的剂量和对异源氯化石蜡挑战的免疫保护作用,并研究了IPL接种氯化石蜡疫苗而无需加强剂的功效。此外,还对接种疫苗后的血清免疫球蛋白 (Ig)Y、粘膜 IgA 和肺部组织病理学进行了研究。通过IPL途径接种CP活疫苗,无论是否接种卵内CpG-ODN,都能显著预防NE(P < 0.0001)。针对 CP 的全身 IgY 和粘膜 IgA 与针对 NE 的保护作用相关。肺实质没有坏死或炎症。通过 IPL 途径接种活体氯化石蜡后,从肺部分离出的氯化石蜡数量较少。通过 IPL 途径接种氯化石蜡活疫苗 2 天后,肺部出现大量 CD8+ T 细胞和巨噬细胞(P < 0.001)。通过 IPL 途径接种氯化石蜡活疫苗比接种灭活的氯化石蜡活疫苗能提供更好的保护。这项研究证明了在肉鸡疫苗接种中利用 GLA 概念的实用性。
Protection of Broiler Chickens Against Necrotic Enteritis by Intrapulmonary Delivery of a Live Clostridium perfringens Vaccine Exploiting the Gut-Lung-Axis Concept.
Clostridium perfringens (CP)-induced necrotic enteritis (NE) is an economically important disease in the broiler chicken industry. The incidence of NE is common in 3-to-6-wk-old broiler chickens, once maternal antibodies start declining. Developing an effective vaccination strategy against NE, preferably delivering a single dose of vaccine at hatch to protect broiler chickens against NE without a booster vaccine, is an enormous challenge. The objective of this study was to induce mucosal immunity in the intestines against NE by intrapulmonary (IPL) delivery of a live CP vaccine at hatch, exploiting the gut-lung-axis (GLA) concept by vaccine delivery following in ovo administration of cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG-ODN) to induce immune cell maturation in the lungs. Experiments were conducted to explore the dose of CP and immune protection against heterologous CP challenge, and to study the efficacy of IPL delivery of a CP vaccine without a booster. Additional studies were conducted to measure serum immunoglobulin (Ig)Y, mucosal IgA, and histopathology of lungs following vaccination. Delivery of a live CP vaccine by the IPL route, with or without in ovo CpG-ODN, provided significant protection against NE (P < 0.0001). Systemic IgY and mucosal IgA against CP were correlated with protection against NE. There was no necrosis or inflammation in the pulmonary parenchyma. There was a low number of CP isolated from the lungs following live CP delivery by the IPL route. A significant influx of (P < 0.001) of CD8+ T cells and macrophages were noted in the lungs 2 days following live CP delivery by the IPL route. IPL delivery of a live CP vaccine, rather than inactivated CP, provided better protection. This study demonstrated the utility in exploiting the GLA concept in vaccine delivery in broiler chickens.