The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, United Kingdom; Institute for Immunology and Infection Research, School of Biological Sciences, Charlotte Auerbach Road, University of Edinburgh, Edinburgh EH9 3FL, United Kingdom.
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, United Kingdom.
Vaccine. 2021 Dec 17;39(51):7413-7420. doi: 10.1016/j.vaccine.2021.10.085. Epub 2021 Nov 17.
Campylobacter jejuni is the leading bacterial cause of human gastroenteritis worldwide and handling or consumption of contaminated poultry meat is the key source of infection. Glycoconjugate vaccines containing the C. jejuni N-glycan have been reported to be partially protective in chickens. However, our previous studies with subunit vaccines comprising the C. jejuni FlpA or SodB proteins with up to two or three C. jejuni N-glycans, respectively, failed to elicit significant protection. In this study, protein glycan coupling technology was used to add up to ten C. jejuni N-glycans onto a detoxified form of Pseudomonas aeruginosa exotoxin A (ExoA). The glycoprotein, G-ExoA, was evaluated for efficacy against intestinal colonisation of White Leghorn chickens by C. jejuni strains M1 and 11168H relative to unglycosylated ExoA. Chickens were challenged with the minimum dose required for reliable colonisation, which was 10 colony-forming units (CFU) for strain M1 and and 10 CFU for strain 11168H. Vaccine-specific serum IgY was detected in chickens vaccinated with both ExoA and G-ExoA. However, no reduction in caecal colonisation by C. jejuni was observed. While the glycan dose achieved with G-ExoA was higher than FlpA- or SodB-based glycoconjugates that were previously evaluated, it was lower than that of glycoconjugates where protection against C. jejuni has been reported, indicating that protection may be highly sensitive to the amount of glycan presented and/or study-specific variables.
空肠弯曲菌是全球导致人类胃肠炎的主要细菌病原体,经手处理或食用受污染的禽肉是主要的感染源。含有空肠弯曲菌 N-聚糖的糖缀合物疫苗已被报道在鸡中具有部分保护作用。然而,我们之前使用含有空肠弯曲菌 FlpA 或 SodB 蛋白的亚单位疫苗的研究,分别含有多达两个或三个空肠弯曲菌 N-聚糖,未能引起显著的保护作用。在这项研究中,使用蛋白聚糖偶联技术将多达 10 个空肠弯曲菌 N-聚糖添加到一种已解毒的铜绿假单胞菌外毒素 A(ExoA)的形式上。相对于未糖基化的 ExoA,评估了糖蛋白 G-ExoA 对白色来航鸡肠道定植的效力,使用了空肠弯曲菌菌株 M1 和 11168H。用可靠定植所需的最低剂量对鸡进行了挑战,M1 菌株需要 10 个菌落形成单位(CFU),11168H 菌株需要 10 CFU。用 ExoA 和 G-ExoA 接种的鸡均检测到疫苗特异性血清 IgY。然而,没有观察到空肠弯曲菌在盲肠中的定植减少。虽然 G-ExoA 中实现的聚糖剂量高于之前评估的基于 FlpA 或 SodB 的糖缀合物,但低于已报道对空肠弯曲菌具有保护作用的糖缀合物,这表明保护作用可能对呈现的聚糖数量和/或特定研究的变量高度敏感。