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基于通用多价大分子抗原(GMMA)的疫苗引发的针对鼠伤寒血清型系统性感染的长期抗菌免疫

Long-Term Anti-Bacterial Immunity against Systemic Infection by Serovar Typhimurium Elicited by a GMMA-Based Vaccine.

作者信息

Fiorino Fabio, Pettini Elena, Koeberling Oliver, Ciabattini Annalisa, Pozzi Gianni, Martin Laura B, Medaglini Donata

机构信息

Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.

GSK Vaccines Institute for Global Health S.r.l., 53100 Siena, Italy.

出版信息

Vaccines (Basel). 2021 May 12;9(5):495. doi: 10.3390/vaccines9050495.

DOI:10.3390/vaccines9050495
PMID:34065899
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8150838/
Abstract

Typhimurium (STm) represents the most prevalent cause of invasive non-typhoidal Salmonella (iNTS) disease, and currently no licensed vaccine is available. In this work we characterized the long-term anti-bacterial immunity elicited by a STm vaccine based on Generalized Modules of Membrane Antigens (GMMA) delivering O:4,5 antigen, using a murine model of systemic infection. Subcutaneous immunization of mice with STmGMMA/Alhydrogel elicited rapid, high, and persistent antigen-specific serum IgG and IgM responses. The serum was bactericidal in vitro. O:4,5-specific IgG were also detected in fecal samples after immunization and positively correlated with IgG observed in intestinal washes. Long-lived plasma cells and O:4,5-specific memory B cells were detected in spleen and bone marrow. After systemic STm challenge, a significant reduction of bacterial load in blood, spleen, and liver, as well as a reduction of circulating neutrophils and G-CSF glycoprotein was observed in STmGMMA/Alhydrogel immunized mice compared to untreated animals. Taken together, these data support the development of a GMMA-based vaccine for prevention of iNTS disease.

摘要

鼠伤寒沙门氏菌(STm)是侵袭性非伤寒沙门氏菌(iNTS)疾病最常见的病因,目前尚无获批的疫苗。在本研究中,我们利用系统性感染的小鼠模型,对基于递送O:4,5抗原的膜抗原通用模块(GMMA)的STm疫苗引发的长期抗菌免疫进行了表征。用STmGMMA/氢氧化铝凝胶对小鼠进行皮下免疫,可引发快速、强烈且持久的抗原特异性血清IgG和IgM反应。该血清在体外具有杀菌作用。免疫后在粪便样本中也检测到了O:4,5特异性IgG,且与肠道灌洗液中观察到的IgG呈正相关。在脾脏和骨髓中检测到了长寿浆细胞和O:4,5特异性记忆B细胞。与未处理的动物相比,在全身性STm攻击后,STmGMMA/氢氧化铝凝胶免疫的小鼠血液、脾脏和肝脏中的细菌载量显著降低,循环中性粒细胞和G-CSF糖蛋白也有所减少。综上所述,这些数据支持开发一种基于GMMA的疫苗来预防iNTS疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a74/8150838/3bb9813d9377/vaccines-09-00495-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a74/8150838/06348a0da864/vaccines-09-00495-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a74/8150838/3a059ebac897/vaccines-09-00495-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a74/8150838/086049ab6fce/vaccines-09-00495-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a74/8150838/237fe3ced265/vaccines-09-00495-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a74/8150838/c7b96f0dfd59/vaccines-09-00495-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a74/8150838/5b26058063fe/vaccines-09-00495-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a74/8150838/3bb9813d9377/vaccines-09-00495-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a74/8150838/06348a0da864/vaccines-09-00495-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a74/8150838/3a059ebac897/vaccines-09-00495-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a74/8150838/086049ab6fce/vaccines-09-00495-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a74/8150838/237fe3ced265/vaccines-09-00495-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a74/8150838/c7b96f0dfd59/vaccines-09-00495-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a74/8150838/5b26058063fe/vaccines-09-00495-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a74/8150838/3bb9813d9377/vaccines-09-00495-g007.jpg

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