Immunogenicity and protective efficacy of nanoparticle formulations of L-SseB against Salmonella infection.

Immunogenicity and protective efficacy of nanoparticle formulations of L-SseB against Salmonella infection.
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DOI:
10.3389/fimmu.2023.1208848
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发表时间:
2023
影响因子:
7.3
通讯作者:
--
中科院分区:
医学2区
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肠沙门氏菌是一种革兰氏阴性病原体,有超过2500种血清型,可感染各种宿主。在人类中,肠球菌引起伤寒或肠胃炎,是一个主要的公共卫生问题。本研究将沙门氏菌致病性岛2ⅲ型分泌系统的尖端蛋白SseB与产肠毒素大肠杆菌的不稳定毒素LTA1亚基融合,合成自佐剂抗原L-SseB。开发了两种独特的纳米颗粒配方,以允许L-SseB的多聚体呈现。用这些制剂接种小鼠,并通过肠链球菌血清变体攻击小鼠来确定保护效果。与角鲨烯纳米乳相比,多糖(壳聚糖)配方具有更好的保护作用。当多糖制剂用于接种家兔时,对肠链球菌的攻击有保护作用。总之,颗粒多糖制剂中的L-SseB似乎是一种有吸引力的候选疫苗,能够广泛保护肠球菌。
Salmonella enterica, a Gram-negative pathogen, has over 2500 serovars that infect a wide range of hosts. In humans, S. enterica causes typhoid or gastroenteritis and is a major public health concern. In this study, SseB (the tip protein of the Salmonella pathogenicity island 2 type III secretion system) was fused with the LTA1 subunit of labile-toxin from enterotoxigenic E. coli to make the self-adjuvanting antigen L-SseB. Two unique nanoparticle formulations were developed to allow multimeric presentation of L-SseB. Mice were vaccinated with these formulations and protective efficacy determined via challenging the mice with S. enterica serovars. The polysaccharide (chitosan) formulation was found to elicit better protection when compared to the squalene nanoemulsion. When the polysaccharide formulation was used to vaccinate rabbits, protection from S. enterica challenge was elicited. In summary, L-SseB in a particulate polysaccharide formulation appears to be an attractive candidate vaccine capable of broad protection against S. enterica.
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