Vaccine Composition Formulated with a Novel <i>Lactobacillus</i>-Derived Exopolysaccharides Adjuvant Provided High Protection against <i>Staphylococcus aureus</i>

A vaccine that effectively targets methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is urgently needed, and has been the focus of studies by numerous research groups, but with limited success to date. Recently, our team found that exopolysaccharides derived from probiotic <i&...

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Main Authors: Haochi Zhang, Na Pan, Cheng Ma, Bohui Liu, Lei Xiu, He Tong, Shouxin Sheng, Yanchen Liang, Haotian Li, Fangfei Ma, Xuemei Bao, Wei Hu, Xiao Wang
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/9/7/775
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author Haochi Zhang
Na Pan
Cheng Ma
Bohui Liu
Lei Xiu
He Tong
Shouxin Sheng
Yanchen Liang
Haotian Li
Fangfei Ma
Xuemei Bao
Wei Hu
Xiao Wang
author_facet Haochi Zhang
Na Pan
Cheng Ma
Bohui Liu
Lei Xiu
He Tong
Shouxin Sheng
Yanchen Liang
Haotian Li
Fangfei Ma
Xuemei Bao
Wei Hu
Xiao Wang
author_sort Haochi Zhang
collection DOAJ
description A vaccine that effectively targets methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is urgently needed, and has been the focus of studies by numerous research groups, but with limited success to date. Recently, our team found that exopolysaccharides derived from probiotic <i>Lactobacillus</i><i>casei</i> strain WXD030 as an adjuvant-formulated OVA could upregulate IFN-γ and IL-17 expression in CD4<sup>+</sup> T cells. In this study, we developed a vaccine (termed rMntC-EPS) composed of <i>S. aureus</i> antigen MntC and <i>Lactobacillus</i> <i>casei</i> exopolysaccharides, which conferred high levels of protection against <i>S. aureus</i> infection. Methods: Six–eight-week-old female mice were vaccinated with purified rMntC-EPS30. The immune protection function of rMntC-EPS30 was assessed by the protective effect of rMntC-EPS30 to <i>S. aureus</i>-induced pulmonary and cutaneous infection in mice, bacterial loads and H&E in injury site, and ELISA for inflammation-related cytokines. The protective mechanism of rMntC-EPS30 was assessed by ELISA for IgG in serum, cytokines in the spleen and lungs of vaccinated mice. In addition, flow cytometry was used for analyzing cellular immune response induced by rMntC-EPS30. For confirmation of our findings, three kinds of mice were used in this study: IL-17A knockout mice, IFN-γ knockout mice and TCRγ/δ knockout mice. Results: rMntC-EPS30 conferred up to 90% protection against <i>S. aureus</i> pulmonary infection and significantly reduced the abscess size in the <i>S. aureus</i> cutaneous model, with clearance of the pathogen. The rMntC-EPS vaccine could induce superior humoral immunity as well as significantly increase IL-17A and IFN-γ production. In addition, we found that rMntC-EPS vaccination induced robust Th 17/γδ T 17 primary and recall responses. Interestingly, this protective effect was distinctly reduced in the IL-17A knockout mice but not in IFN-γ knockout mice. Moreover, in TCRγ/δ knockout mice, rMntC-EPS vaccination neither increased IL-17A secretion nor provided effective protection against <i>S. aureus</i> infection. Conclusions: These data demonstrated that the rMntC formulated with a novel <i>Lactobacillus</i>-derived Exopolysaccharides adjuvant provided high protection against <i>Staphylococcus aureus</i>. The rMntC-EPS vaccine induced γδ T cells and IL-17A might play substantial roles in anti-<i>S. aureus</i> immunity. Our findings provided direct evidence that rMntC-EPS vaccine is a promising candidate for future clinical application against <i>S. aureus</i>-induced pulmonary and cutaneous infection.
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spelling doaj.art-9c635a85336d445d99941d345890aef72023-11-22T05:12:51ZengMDPI AGVaccines2076-393X2021-07-019777510.3390/vaccines9070775Vaccine Composition Formulated with a Novel <i>Lactobacillus</i>-Derived Exopolysaccharides Adjuvant Provided High Protection against <i>Staphylococcus aureus</i>Haochi Zhang0Na Pan1Cheng Ma2Bohui Liu3Lei Xiu4He Tong5Shouxin Sheng6Yanchen Liang7Haotian Li8Fangfei Ma9Xuemei Bao10Wei Hu11Xiao Wang12State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, ChinaA vaccine that effectively targets methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is urgently needed, and has been the focus of studies by numerous research groups, but with limited success to date. Recently, our team found that exopolysaccharides derived from probiotic <i>Lactobacillus</i><i>casei</i> strain WXD030 as an adjuvant-formulated OVA could upregulate IFN-γ and IL-17 expression in CD4<sup>+</sup> T cells. In this study, we developed a vaccine (termed rMntC-EPS) composed of <i>S. aureus</i> antigen MntC and <i>Lactobacillus</i> <i>casei</i> exopolysaccharides, which conferred high levels of protection against <i>S. aureus</i> infection. Methods: Six–eight-week-old female mice were vaccinated with purified rMntC-EPS30. The immune protection function of rMntC-EPS30 was assessed by the protective effect of rMntC-EPS30 to <i>S. aureus</i>-induced pulmonary and cutaneous infection in mice, bacterial loads and H&E in injury site, and ELISA for inflammation-related cytokines. The protective mechanism of rMntC-EPS30 was assessed by ELISA for IgG in serum, cytokines in the spleen and lungs of vaccinated mice. In addition, flow cytometry was used for analyzing cellular immune response induced by rMntC-EPS30. For confirmation of our findings, three kinds of mice were used in this study: IL-17A knockout mice, IFN-γ knockout mice and TCRγ/δ knockout mice. Results: rMntC-EPS30 conferred up to 90% protection against <i>S. aureus</i> pulmonary infection and significantly reduced the abscess size in the <i>S. aureus</i> cutaneous model, with clearance of the pathogen. The rMntC-EPS vaccine could induce superior humoral immunity as well as significantly increase IL-17A and IFN-γ production. In addition, we found that rMntC-EPS vaccination induced robust Th 17/γδ T 17 primary and recall responses. Interestingly, this protective effect was distinctly reduced in the IL-17A knockout mice but not in IFN-γ knockout mice. Moreover, in TCRγ/δ knockout mice, rMntC-EPS vaccination neither increased IL-17A secretion nor provided effective protection against <i>S. aureus</i> infection. Conclusions: These data demonstrated that the rMntC formulated with a novel <i>Lactobacillus</i>-derived Exopolysaccharides adjuvant provided high protection against <i>Staphylococcus aureus</i>. The rMntC-EPS vaccine induced γδ T cells and IL-17A might play substantial roles in anti-<i>S. aureus</i> immunity. Our findings provided direct evidence that rMntC-EPS vaccine is a promising candidate for future clinical application against <i>S. aureus</i>-induced pulmonary and cutaneous infection.https://www.mdpi.com/2076-393X/9/7/775exopolysaccharidesvaccine<i>S. aureus</i>γδ T cellsIL-17A
spellingShingle Haochi Zhang
Na Pan
Cheng Ma
Bohui Liu
Lei Xiu
He Tong
Shouxin Sheng
Yanchen Liang
Haotian Li
Fangfei Ma
Xuemei Bao
Wei Hu
Xiao Wang
Vaccine Composition Formulated with a Novel <i>Lactobacillus</i>-Derived Exopolysaccharides Adjuvant Provided High Protection against <i>Staphylococcus aureus</i>
Vaccines
exopolysaccharides
vaccine
<i>S. aureus</i>
γδ T cells
IL-17A
title Vaccine Composition Formulated with a Novel <i>Lactobacillus</i>-Derived Exopolysaccharides Adjuvant Provided High Protection against <i>Staphylococcus aureus</i>
title_full Vaccine Composition Formulated with a Novel <i>Lactobacillus</i>-Derived Exopolysaccharides Adjuvant Provided High Protection against <i>Staphylococcus aureus</i>
title_fullStr Vaccine Composition Formulated with a Novel <i>Lactobacillus</i>-Derived Exopolysaccharides Adjuvant Provided High Protection against <i>Staphylococcus aureus</i>
title_full_unstemmed Vaccine Composition Formulated with a Novel <i>Lactobacillus</i>-Derived Exopolysaccharides Adjuvant Provided High Protection against <i>Staphylococcus aureus</i>
title_short Vaccine Composition Formulated with a Novel <i>Lactobacillus</i>-Derived Exopolysaccharides Adjuvant Provided High Protection against <i>Staphylococcus aureus</i>
title_sort vaccine composition formulated with a novel i lactobacillus i derived exopolysaccharides adjuvant provided high protection against i staphylococcus aureus i
topic exopolysaccharides
vaccine
<i>S. aureus</i>
γδ T cells
IL-17A
url https://www.mdpi.com/2076-393X/9/7/775
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