The Application of a Proteoliposome Adjuvant System in the Development of a Campylobacter Jejuni Vaccine

Barbara Rickaby , Nelson F. Eng , Annika Flint , Alain Stintzi , Francisco Diaz-Mitoma
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引用次数: 2

Abstract

The high incidence of Campylobacter jejuni-associated diarrhoea, the increase in the frequency of drug resistance, and the correlation between infection and Guillain-Barré syndrome, has heightened the need to develop effective anti-Campylobacter vaccines. Due to the risk of auto-immunity, vaccinations using whole-cells or attenuated cells are not clinical candidates. Subunit vaccines are viable alternatives and have been shown to be effective against other enteric pathogens. This research tested the efficacy of the catalase (KatA) from C. jejuni as a potential vaccine candidate against the pathogen. The protein was found to be immunogenic following an intramuscular murine immunization. A balanced IgG1/IgG2a response was generated when KatA was co-administered with monophosphoryl lipid A and alum. The antibodies elicited reduced the adhesion and invasion of C. jejuni to human epithelial cells (IECs) in vitro. The next phase of testing will be in combination with a proteoliposome (PL) derived from the outer membrane of V. cholerae. PL nano-vesicles were generated with an average size of ≈70 nm and had a zeta potential of ≈-40 mV.

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蛋白脂质体佐剂体系在空肠弯曲杆菌疫苗研制中的应用
肠弯曲杆菌相关腹泻的高发病率、耐药频率的增加以及感染与格林-巴-罗伊斯综合征之间的相关性,提高了开发有效的抗弯曲杆菌疫苗的必要性。由于自身免疫的风险,使用全细胞或减毒细胞接种疫苗不是临床候选。亚单位疫苗是可行的替代方案,并已被证明对其他肠道病原体有效。本研究测试了空肠梭菌过氧化氢酶(KatA)作为一种潜在的疫苗候选物的有效性。在小鼠肌内免疫后发现该蛋白具有免疫原性。当KatA与单磷酰脂质A和明矾共同给药时,产生平衡的IgG1/IgG2a反应。体外诱导的抗体可降低空肠梭菌对人上皮细胞的粘附和侵袭。下一阶段的测试将与从霍乱弧菌外膜提取的蛋白脂质体(PL)结合使用。生成的PL纳米囊泡平均尺寸约为70 nm, zeta电位约为-40 mV。
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