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在动物模型中，荚膜多糖在引发针对异源血清型的功能性免疫反应方面起着关键作用。

decorations in play a key role in eliciting functional immune responses against heterologous serovars in animal models.

机构信息

GSK, Siena, Italy.

GSK Vaccines Institute for Global Health (GVGH), Siena, Italy.

出版信息

Front Cell Infect Microbiol. 2024 Feb 29;14:1347813. doi: 10.3389/fcimb.2024.1347813. eCollection 2024.

DOI:10.3389/fcimb.2024.1347813
PMID:38487353
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10937413/
Abstract

INTRODUCTION

Different serovars of Salmonella enterica cause systemic diseases in humans including enteric fever, caused by S. Typhi and S. Paratyphi A, and invasive nontyphoidal salmonellosis (iNTS), caused mainly by S. Typhimurium and S. Enteritidis. No vaccines are yet available against paratyphoid fever and iNTS but different strategies, based on the immunodominant O-Antigen component of the lipopolysaccharide, are currently being tested. The O-Antigens of S. enterica serovars share structural features including the backbone comprising mannose, rhamnose and galactose as well as further modifications such as O-acetylation and glucosylation. The importance of these O-Antigen decorations for the induced immunogenicity and cross-reactivity has been poorly characterized.

METHODS

These immunological aspects were investigated in this study using Generalized Modules for Membrane Antigens (GMMA) as delivery systems for the different O-Antigen variants. This platform allowed the rapid generation and in vivo testing of defined and controlled polysaccharide structures through genetic manipulation of the O-Antigen biosynthetic genes.

RESULTS

Results from mice and rabbit immunization experiments highlighted the important role played by secondary O-Antigen decorations in the induced immunogenicity. Moreover, molecular modeling of O-Antigen conformations corroborated the likelihood of cross-protection between S. enterica serovars.

DISCUSSION

Such results, if confirmed in humans, could have a great impact on the design of a simplified vaccine composition able to maximize functional immune responses against clinically relevant Salmonella enterica serovars.

摘要

简介

不同血清型的沙门氏菌会引起人类全身性疾病，包括伤寒，由伤寒沙门氏菌和甲型副伤寒沙门氏菌引起，以及侵袭性非伤寒性沙门氏菌病（iNTS），主要由鼠伤寒沙门氏菌和肠炎沙门氏菌引起。目前还没有针对副伤寒和 iNTS 的疫苗，但基于脂多糖免疫显性 O-抗原成分的不同策略正在进行测试。沙门氏菌血清型的 O-抗原具有结构特征，包括由甘露糖、鼠李糖和半乳糖组成的骨架，以及进一步的修饰，如 O-乙酰化和葡糖基化。这些 O-抗原修饰对诱导免疫原性和交叉反应性的重要性尚未得到充分描述。

方法

本研究使用通用膜抗原模块（GMMA）作为不同 O-抗原变体的递送系统，研究了这些免疫学方面。该平台允许通过 O-抗原生物合成基因的遗传操作，快速生成和体内测试定义和受控的多糖结构。

结果

来自小鼠和兔免疫实验的结果突出了次级 O-抗原修饰在诱导免疫原性中所起的重要作用。此外，O-抗原构象的分子建模证实了沙门氏菌血清型之间存在交叉保护的可能性。

讨论

如果在人类中得到证实，这些结果可能会对简化疫苗成分的设计产生重大影响，使能够针对临床上相关的沙门氏菌血清型最大限度地发挥功能性免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4c/10937413/d3be9351e839/fcimb-14-1347813-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4c/10937413/e32793c57c4b/fcimb-14-1347813-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4c/10937413/bdc4455ac476/fcimb-14-1347813-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4c/10937413/bc3955f17c0c/fcimb-14-1347813-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4c/10937413/e37a928b3a0e/fcimb-14-1347813-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4c/10937413/d3be9351e839/fcimb-14-1347813-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4c/10937413/e32793c57c4b/fcimb-14-1347813-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4c/10937413/bdc4455ac476/fcimb-14-1347813-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4c/10937413/bc3955f17c0c/fcimb-14-1347813-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4c/10937413/e37a928b3a0e/fcimb-14-1347813-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b4c/10937413/d3be9351e839/fcimb-14-1347813-g005.jpg

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