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口服突变体作为基于 的疫苗载体用于预防和逆转 1 型糖尿病。

Oral Mutant as a Carrier for a -Based Vaccine for Prevention and Reversal of Type 1 Diabetes.

机构信息

Department of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, United States.

Division of Microbiology, University of Osnabrück, Osnabrück, Germany.

出版信息

Front Immunol. 2021 May 24;12:667897. doi: 10.3389/fimmu.2021.667897. eCollection 2021.

DOI:10.3389/fimmu.2021.667897
PMID:34108968
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8181392/
Abstract

A therapy that includes an oral vaccine for type 1 diabetes (T1D) using live attenuated MvP728 (ΔΔ), cytokines (IL10 and TGFβ) and preproinsulin (PPI) antigen in combination with a sub-therapeutic dose of anti-CD3 mAb was developed by our team. The vaccine combination therapy reduced insulitis and prevented and reversed diabetes in non-obese diabetic (NOD) mice. Here, we show the effectiveness of an alternative mutant (Δ) as a carrier strain, which is anticipated to have lower risks of an inflammatory response and septicemia as a result of modification in the lipopolysaccharide (LPS) detoxification of lipid A. This mutant strain proved to have highly reduced pathogenic side effects. strain Δ expressed autoantigens and in combination with cytokines and anti-CD3 mAb, successfully prevented and reversed T1D to levels comparable to the previously used carrier strain ΔΔ. Additionally, the mutant resulted in higher rates of host cell infection. These results further demonstrate the potential of an oral -based combined therapy in the treatment of early T1D.

摘要

我们团队开发了一种包括口服疫苗的疗法，用于 1 型糖尿病（T1D），该疫苗使用活减毒 MvP728（ΔΔ）、细胞因子（IL10 和 TGFβ）和前胰岛素原（PPI）抗原，联合亚治疗剂量的抗 CD3 mAb。疫苗联合疗法减轻了胰岛炎，并预防和逆转了非肥胖型糖尿病（NOD）小鼠的糖尿病。在这里，我们展示了另一种突变体（Δ）作为载体菌株的有效性，预计由于脂多糖（LPS）的脂质 A 解毒作用的改变，该突变体菌株的炎症反应和败血症的风险更低。该突变株被证明具有高度降低的致病性副作用。Δ 株表达自身抗原，并与细胞因子和抗 CD3 mAb 联合使用，成功预防和逆转了 T1D，达到与之前使用的载体菌株 ΔΔ 相当的水平。此外，突变株导致更高的宿主细胞感染率。这些结果进一步证明了基于口服的联合疗法在治疗早期 T1D 方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b99/8181392/49159eeae3e5/fimmu-12-667897-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b99/8181392/c7730ebb2a55/fimmu-12-667897-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b99/8181392/77d695475e34/fimmu-12-667897-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b99/8181392/7c65c28f35e5/fimmu-12-667897-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b99/8181392/3f619c6c6e0d/fimmu-12-667897-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b99/8181392/07828893ce60/fimmu-12-667897-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b99/8181392/49159eeae3e5/fimmu-12-667897-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b99/8181392/c7730ebb2a55/fimmu-12-667897-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b99/8181392/77d695475e34/fimmu-12-667897-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b99/8181392/7c65c28f35e5/fimmu-12-667897-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b99/8181392/3f619c6c6e0d/fimmu-12-667897-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b99/8181392/07828893ce60/fimmu-12-667897-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b99/8181392/49159eeae3e5/fimmu-12-667897-g006.jpg

相似文献

[1]
Oral Mutant as a Carrier for a -Based Vaccine for Prevention and Reversal of Type 1 Diabetes.

Front Immunol. 2021

[2]
Reversal of New Onset Type 1 Diabetes by Oral -Based Combination Therapy and Mediated by Regulatory T-Cells in NOD Mice.

Front Immunol. 2019-2-26

[3]
Factors affecting Salmonella-based combination immunotherapy for prevention of type 1 diabetes in non-obese diabetic mice.

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[4]
An oral vaccine for type 1 diabetes based on live attenuated Salmonella.

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[5]
Tracking of an Oral -Based Vaccine for Type 1 Diabetes in Non-obese Diabetic Mice.

Front Immunol. 2020

[6]
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[7]
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[8]
Protective Immunity Elicited by Oral Immunization of Mice with Serovar Typhimurium Braun Lipoprotein (Lpp) and Acetyltransferase (MsbB) Mutants.

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[9]
Mucosal administration of CD3-specific monoclonal antibody inhibits diabetes in NOD mice and in a preclinical mouse model transgenic for the CD3 epsilon chain.

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[10]
Palmitoylation state impacts induction of innate and acquired immunity by the Salmonella enterica serovar typhimurium msbB mutant.

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引用本文的文献

[1]
-Based Vaccine: A Promising Strategy for Type 1 Diabetes.

Vaccines (Basel). 2025-4-14

[2]
Role of Gene in Physiology and Pathogenicity of .

Microorganisms. 2025-2-10

[3]
Reversal of diabetes by an oral Salmonella-based vaccine in acute and progressive diabetes in NOD mice.

PLoS One. 2024

[4]
Mechanism of Action of Oral -Based Vaccine to Prevent and Reverse Type 1 Diabetes in NOD Mice.

Vaccines (Basel). 2024-3-6

[5]
Transformed Salmonella typhimurium SL7207/pcDNA-CCOL2A1 as an orally administered DNA vaccine.

AMB Express. 2024-1-9

[6]
Changes in the gut microbiota of NOD mice in response to an oral Salmonella-based vaccine against type 1 diabetes.

PLoS One. 2023

[7]
Engineering live attenuated vaccines: Old dogs learning new tricks.

J Transl Autoimmun. 2023-3-27

本文引用的文献

[1]
Tracking of an Oral -Based Vaccine for Type 1 Diabetes in Non-obese Diabetic Mice.

Front Immunol. 2020

[2]
Reversal of New Onset Type 1 Diabetes by Oral -Based Combination Therapy and Mediated by Regulatory T-Cells in NOD Mice.

Front Immunol. 2019-2-26

[3]
Factors affecting Salmonella-based combination immunotherapy for prevention of type 1 diabetes in non-obese diabetic mice.

Vaccine. 2018-11-8

[4]
Protective Immunity Elicited by Oral Immunization of Mice with Serovar Typhimurium Braun Lipoprotein (Lpp) and Acetyltransferase (MsbB) Mutants.

Front Cell Infect Microbiol. 2016-11-10

[5]
Efficiency of conditionally attenuated Salmonella enterica serovar Typhimurium in bacterium-mediated tumor therapy.

mBio. 2015-4-14

[6]
Salmonella enterica serovar Typhimurium ΔmsbB triggers exacerbated inflammation in Nod2 deficient mice.

PLoS One. 2014-11-25

[7]
Flippase (FLP) recombinase-mediated marker recycling in the dermatophyte Arthroderma vanbreuseghemii.

Microbiology (Reading). 2014-10

[8]
An oral vaccine for type 1 diabetes based on live attenuated Salmonella.

Vaccine. 2014-3-12

[9]
Palmitoylation state impacts induction of innate and acquired immunity by the Salmonella enterica serovar typhimurium msbB mutant.

Infect Immun. 2011-9-19

[10]
Effect of deletion of genes involved in lipopolysaccharide core and O-antigen synthesis on virulence and immunogenicity of Salmonella enterica serovar typhimurium.

Infect Immun. 2011-7-18

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