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三价外膜囊泡基组合疫苗候选物诱导成年小鼠对弯曲杆菌和侵袭性非伤寒沙门氏菌的保护性免疫。

Trivalent outer membrane vesicles-based combination vaccine candidate induces protective immunity against Campylobacter and invasive non-typhoidal Salmonella in adult mice.

机构信息

Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, P-33 CIT Road, Scheme-XM, Beliaghata, Kolkata, 700010, India.

Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, 65211, USA.

出版信息

Med Microbiol Immunol. 2024 Oct 15;213(1):21. doi: 10.1007/s00430-024-00805-z.

Abstract

Campylobacter and invasive non-typhoidal Salmonella (iNTS) are among the most common causative agents of gastroenteritis worldwide. As of now, no single combination licensed vaccine is available for public health use against both iNTS and Campylobacter species. Outer-membrane vesicles (OMVs) are nanoscale proteoliposomes released from the surface of gram-negative bacteria during log phase and harbor a variety of immunogenic proteins. Based on epidemiology of infections, we formulated a novel trivalent outer membrane vesicles (TOMVs)-based vaccine candidate against Campylobacter jejuni (CJ), Salmonella Typhimurium (ST) and Salmonella Enteritidis (SE). Isolated OMVs from CJ, ST and SE were combined in equal ratios for formulation of TOMVs and 5 µg of the developed vaccine candidate was used for intraperitoneal immunization of adult BALB/c mice. Immunization with TOMVs significantly activated both the humoral and cellular arm of adaptive immune response. Robust bactericidal effect was elicited by TOMVs immunized adult mice sera. TOMVs immunization induced long-term protective efficacy against CJ, ST and SE infections in mice. The study illustrates the ability of TOMVs-based combination immunogen in eliciting broad-spectrum protective immunity against prevalent Campylobacter and iNTS pathogens. According to the findings, TOMVs can work as a potent combination-based acellular vaccine candidate for amelioration of Campylobacter and iNTS-mediated gastroenteritis.

摘要

空肠弯曲菌和侵袭性非伤寒沙门氏菌(iNTS)是全球最常见的胃肠炎病原体之一。截至目前,尚无针对 iNTS 和弯曲菌属的单一联合许可疫苗可用于公共卫生。外膜囊泡(OMVs)是革兰氏阴性菌在对数生长期从表面释放的纳米级脂蛋白,含有多种免疫原性蛋白。基于感染的流行病学,我们针对空肠弯曲菌(CJ)、鼠伤寒沙门氏菌(ST)和肠炎沙门氏菌(SE)制定了一种新型三价外膜囊泡(TOMVs)疫苗候选物。从 CJ、ST 和 SE 中分离的 OMVs 以相等的比例组合用于制备 TOMVs,并用 5µg 开发的疫苗候选物对成年 BALB/c 小鼠进行腹腔免疫接种。TOMVs 免疫显著激活了适应性免疫反应的体液和细胞臂。TOMVs 免疫的成年小鼠血清引起了强大的杀菌作用。TOMVs 免疫诱导了对 CJ、ST 和 SE 感染的长期保护效力。该研究说明了基于 TOMVs 的组合免疫原在引发针对流行的弯曲菌和 iNTS 病原体的广谱保护免疫方面的能力。根据研究结果,TOMVs 可以作为一种有效的基于组合的非细胞疫苗候选物,用于改善弯曲菌和 iNTS 介导的胃肠炎。

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