Oral Immunisation With Non‐GMO Surface Displayed SARS‐CoV‐2 Spike Epitopes on Bacteria‐Like Particles Provokes Robust Humoral and Cellular Immune Responses, and Modulated the Gut Microbiome in Mice

ABSTRACT The coronavirus disease 2019 (COVID‐19) is a fatal disease caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). To date, several vaccines have been developed to combat the spread of this virus. Mucosal vaccines using food‐grade bacteria, such as Lactobacillus spp., are pr...

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Main Authors: Robie Vasquez, Ji Hoon Song, Remilyn M. Mendoza, In‐Chan Hwang, Bernadette B. Bagon, Lars Engstrand, Valerie Diane Valeriano, Dae‐Kyung Kang
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Microbial Biotechnology
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Online Access:https://doi.org/10.1111/1751-7915.70073
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author Robie Vasquez
Ji Hoon Song
Remilyn M. Mendoza
In‐Chan Hwang
Bernadette B. Bagon
Lars Engstrand
Valerie Diane Valeriano
Dae‐Kyung Kang
author_facet Robie Vasquez
Ji Hoon Song
Remilyn M. Mendoza
In‐Chan Hwang
Bernadette B. Bagon
Lars Engstrand
Valerie Diane Valeriano
Dae‐Kyung Kang
author_sort Robie Vasquez
collection DOAJ
description ABSTRACT The coronavirus disease 2019 (COVID‐19) is a fatal disease caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). To date, several vaccines have been developed to combat the spread of this virus. Mucosal vaccines using food‐grade bacteria, such as Lactobacillus spp., are promising strategies for developing safe and effective vaccines against SARS‐CoV‐2. In this study, we designed a non‐GMO surface‐displayed SARS‐CoV‐2 spike S1 epitope on Limosilactobacillus fermentum‐derived bacteria‐like particles (BLPs). After that, we evaluated its efficacy to induce immune responses in immunocompetent mice. Moreover, we examined the influence of oral immunisation on the gut microbiome and microbiota metabolites. Twenty‐eight 6‐week‐old male C57BL/6 mice were orally immunised with the following: PBS (control), Lm. fermentum‐derived BLPs only, BLPs displaying SARS‐CoV‐2 spike S1‐2, or BLPs displaying SARS‐CoV‐2 spike S1‐3 epitopes. Our results showed that mucosal immunisation of mice with surface‐displayed SARS‐CoV‐2 spike epitopes provoked high‐level secretory IgA and systemic IgG production. Moreover, the immunisation exhibited a Th1‐like immune response, characterised by an elevated IgG2a‐to‐IgG1 ratio and high antiviral IFN‐γ production. In addition, we observed gut microbiome modulation and increased butyrate production in immunised mice. Overall, the use of Lm. fermentum‐derived BLPs and the anchor CshA to display SARS‐CoV‐2 spike S1epitopes is a promising novel strategy in developing a cost‐effective, non‐GMO mucosal vaccine alternative against SARS‐CoV‐2.
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spelling doaj-art-689e9535c170453b9db14d6f8dee6ccc2025-01-31T06:26:35ZengWileyMicrobial Biotechnology1751-79152025-01-01181n/an/a10.1111/1751-7915.70073Oral Immunisation With Non‐GMO Surface Displayed SARS‐CoV‐2 Spike Epitopes on Bacteria‐Like Particles Provokes Robust Humoral and Cellular Immune Responses, and Modulated the Gut Microbiome in MiceRobie Vasquez0Ji Hoon Song1Remilyn M. Mendoza2In‐Chan Hwang3Bernadette B. Bagon4Lars Engstrand5Valerie Diane Valeriano6Dae‐Kyung Kang7Department of Animal Biotechnology Dankook University Cheonan KoreaDepartment of Animal Biotechnology Dankook University Cheonan KoreaDepartment of Animal Biotechnology Dankook University Cheonan KoreaDepartment of Animal Biotechnology Dankook University Cheonan KoreaDepartment of Animal Biotechnology Dankook University Cheonan KoreaDepartment of Microbiology, Tumor and Cell Biology, Centre for Translational Microbiome Research (CTMR) Karolinska Institutet Stockholm SwedenDepartment of Microbiology, Tumor and Cell Biology, Centre for Translational Microbiome Research (CTMR) Karolinska Institutet Stockholm SwedenDepartment of Animal Biotechnology Dankook University Cheonan KoreaABSTRACT The coronavirus disease 2019 (COVID‐19) is a fatal disease caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). To date, several vaccines have been developed to combat the spread of this virus. Mucosal vaccines using food‐grade bacteria, such as Lactobacillus spp., are promising strategies for developing safe and effective vaccines against SARS‐CoV‐2. In this study, we designed a non‐GMO surface‐displayed SARS‐CoV‐2 spike S1 epitope on Limosilactobacillus fermentum‐derived bacteria‐like particles (BLPs). After that, we evaluated its efficacy to induce immune responses in immunocompetent mice. Moreover, we examined the influence of oral immunisation on the gut microbiome and microbiota metabolites. Twenty‐eight 6‐week‐old male C57BL/6 mice were orally immunised with the following: PBS (control), Lm. fermentum‐derived BLPs only, BLPs displaying SARS‐CoV‐2 spike S1‐2, or BLPs displaying SARS‐CoV‐2 spike S1‐3 epitopes. Our results showed that mucosal immunisation of mice with surface‐displayed SARS‐CoV‐2 spike epitopes provoked high‐level secretory IgA and systemic IgG production. Moreover, the immunisation exhibited a Th1‐like immune response, characterised by an elevated IgG2a‐to‐IgG1 ratio and high antiviral IFN‐γ production. In addition, we observed gut microbiome modulation and increased butyrate production in immunised mice. Overall, the use of Lm. fermentum‐derived BLPs and the anchor CshA to display SARS‐CoV‐2 spike S1epitopes is a promising novel strategy in developing a cost‐effective, non‐GMO mucosal vaccine alternative against SARS‐CoV‐2.https://doi.org/10.1111/1751-7915.70073bacteria‐like particlesCOVID‐19immune responselactobacillusmicrobiomemucosal vaccine
spellingShingle Robie Vasquez
Ji Hoon Song
Remilyn M. Mendoza
In‐Chan Hwang
Bernadette B. Bagon
Lars Engstrand
Valerie Diane Valeriano
Dae‐Kyung Kang
Oral Immunisation With Non‐GMO Surface Displayed SARS‐CoV‐2 Spike Epitopes on Bacteria‐Like Particles Provokes Robust Humoral and Cellular Immune Responses, and Modulated the Gut Microbiome in Mice
Microbial Biotechnology
bacteria‐like particles
COVID‐19
immune response
lactobacillus
microbiome
mucosal vaccine
title Oral Immunisation With Non‐GMO Surface Displayed SARS‐CoV‐2 Spike Epitopes on Bacteria‐Like Particles Provokes Robust Humoral and Cellular Immune Responses, and Modulated the Gut Microbiome in Mice
title_full Oral Immunisation With Non‐GMO Surface Displayed SARS‐CoV‐2 Spike Epitopes on Bacteria‐Like Particles Provokes Robust Humoral and Cellular Immune Responses, and Modulated the Gut Microbiome in Mice
title_fullStr Oral Immunisation With Non‐GMO Surface Displayed SARS‐CoV‐2 Spike Epitopes on Bacteria‐Like Particles Provokes Robust Humoral and Cellular Immune Responses, and Modulated the Gut Microbiome in Mice
title_full_unstemmed Oral Immunisation With Non‐GMO Surface Displayed SARS‐CoV‐2 Spike Epitopes on Bacteria‐Like Particles Provokes Robust Humoral and Cellular Immune Responses, and Modulated the Gut Microbiome in Mice
title_short Oral Immunisation With Non‐GMO Surface Displayed SARS‐CoV‐2 Spike Epitopes on Bacteria‐Like Particles Provokes Robust Humoral and Cellular Immune Responses, and Modulated the Gut Microbiome in Mice
title_sort oral immunisation with non gmo surface displayed sars cov 2 spike epitopes on bacteria like particles provokes robust humoral and cellular immune responses and modulated the gut microbiome in mice
topic bacteria‐like particles
COVID‐19
immune response
lactobacillus
microbiome
mucosal vaccine
url https://doi.org/10.1111/1751-7915.70073
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