Mucosal immunization with Lactiplantibacillus plantarum-displaying recombinant SARS-CoV-2 epitopes on the surface induces humoral and mucosal immune responses in mice
Abstract Background The use of probiotic lactic acid bacteria as a mucosal vaccine vector is considered a promising alternative compared to the use of other microorganisms because of its “Generally Regarded as Safe” status, its potential adjuvant properties, and its tolerogenicity to the host. Sever...
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Microbial Cell Factories |
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| Online Access: | https://doi.org/10.1186/s12934-023-02100-7 |
| _version_ | 1797827222488219648 |
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| author | In-Chan Hwang Valerie Diane Valeriano Ji Hoon Song Marcela Pereira Ju Kyoung Oh Kyudong Han Lars Engstrand Dae-Kyung Kang |
| author_facet | In-Chan Hwang Valerie Diane Valeriano Ji Hoon Song Marcela Pereira Ju Kyoung Oh Kyudong Han Lars Engstrand Dae-Kyung Kang |
| author_sort | In-Chan Hwang |
| collection | DOAJ |
| description | Abstract Background The use of probiotic lactic acid bacteria as a mucosal vaccine vector is considered a promising alternative compared to the use of other microorganisms because of its “Generally Regarded as Safe” status, its potential adjuvant properties, and its tolerogenicity to the host. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), is highly transmissible and pathogenic. This study aimed to determine the potential of Lactiplantibacillus plantarum expressing SARS-CoV-2 epitopes as a mucosal vaccine against SARS-CoV-2. Results In this study, the possible antigenic determinants of the spike (S1–1, S1–2, S1–3, and S1–4), membrane (ME1 and ME2), and envelope (E) proteins of SARS-CoV-2 were predicted, and recombinant L. plantarum strains surface-displaying these epitopes were constructed. Subsequently, the immune responses induced by these recombinant strains were compared in vitro and in vivo. Most surface-displayed epitopes induced pro-inflammatory cytokines [tumor necrosis factor alpha (TNF-α and interleukin (IL)-6] and anti-inflammatory cytokines (IL-10) in lipopolysaccharide-induced RAW 264.7, with the highest anti-inflammatory to pro-inflammatory cytokine ratio in the S1–1 and S1–2 groups, followed by that in the S1–3 group. When orally administered of recombinant L. plantarum expressing SARS-CoV-2 epitopes in mice, all epitopes most increased the expression of IL-4, along with induced levels of TNF-α, interferon-gamma, and IL-10, specifically in spike protein groups. Thus, the surface expression of epitopes from the spike S1 protein in L. plantarum showed potential immunoregulatory effects, suggesting its ability to potentially circumvent hyperinflammatory states relevant to monocyte/macrophage cell activation. At 35 days post immunization (dpi), serum IgG levels showed a marked increase in the S1–1, S1–2, and S1–3 groups. Fecal IgA levels increased significantly from 21 dpi in all the antigen groups, but the boosting effect after 35 dpi was explicitly observed in the S1–1, S1–2, and S1–3 groups. Thus, the oral administration of SARS-CoV-2 antigens into mice induced significant humoral and mucosal immune responses. Conclusion This study suggests that L. plantarum is a potential vector that can effectively deliver SARS-CoV-2 epitopes to intestinal mucosal sites and could serve as a novel approach for SARS-CoV-2 mucosal vaccine development. |
| first_indexed | 2024-04-09T12:44:47Z |
| format | Article |
| id | doaj.art-162be1f5d7a942318cda29181a8e2ec6 |
| institution | Directory Open Access Journal |
| issn | 1475-2859 |
| language | English |
| last_indexed | 2024-04-09T12:44:47Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbial Cell Factories |
| spelling | doaj.art-162be1f5d7a942318cda29181a8e2ec62023-05-14T11:31:55ZengBMCMicrobial Cell Factories1475-28592023-05-0122111410.1186/s12934-023-02100-7Mucosal immunization with Lactiplantibacillus plantarum-displaying recombinant SARS-CoV-2 epitopes on the surface induces humoral and mucosal immune responses in miceIn-Chan Hwang0Valerie Diane Valeriano1Ji Hoon Song2Marcela Pereira3Ju Kyoung Oh4Kyudong Han5Lars Engstrand6Dae-Kyung Kang7Department of Animal Resources Science, Dankook UniversityDepartment of Microbiology, Tumor and Cell Biology, Karolinska InstitutetDepartment of Animal Resources Science, Dankook UniversityDepartment of Microbiology, Tumor and Cell Biology, Karolinska InstitutetDepartment of Microbiology, Tumor and Cell Biology, Karolinska InstitutetDepartment of Microbiology, College of Science and Technology, Dankook UniversityDepartment of Microbiology, Tumor and Cell Biology, Karolinska InstitutetDepartment of Animal Resources Science, Dankook UniversityAbstract Background The use of probiotic lactic acid bacteria as a mucosal vaccine vector is considered a promising alternative compared to the use of other microorganisms because of its “Generally Regarded as Safe” status, its potential adjuvant properties, and its tolerogenicity to the host. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), is highly transmissible and pathogenic. This study aimed to determine the potential of Lactiplantibacillus plantarum expressing SARS-CoV-2 epitopes as a mucosal vaccine against SARS-CoV-2. Results In this study, the possible antigenic determinants of the spike (S1–1, S1–2, S1–3, and S1–4), membrane (ME1 and ME2), and envelope (E) proteins of SARS-CoV-2 were predicted, and recombinant L. plantarum strains surface-displaying these epitopes were constructed. Subsequently, the immune responses induced by these recombinant strains were compared in vitro and in vivo. Most surface-displayed epitopes induced pro-inflammatory cytokines [tumor necrosis factor alpha (TNF-α and interleukin (IL)-6] and anti-inflammatory cytokines (IL-10) in lipopolysaccharide-induced RAW 264.7, with the highest anti-inflammatory to pro-inflammatory cytokine ratio in the S1–1 and S1–2 groups, followed by that in the S1–3 group. When orally administered of recombinant L. plantarum expressing SARS-CoV-2 epitopes in mice, all epitopes most increased the expression of IL-4, along with induced levels of TNF-α, interferon-gamma, and IL-10, specifically in spike protein groups. Thus, the surface expression of epitopes from the spike S1 protein in L. plantarum showed potential immunoregulatory effects, suggesting its ability to potentially circumvent hyperinflammatory states relevant to monocyte/macrophage cell activation. At 35 days post immunization (dpi), serum IgG levels showed a marked increase in the S1–1, S1–2, and S1–3 groups. Fecal IgA levels increased significantly from 21 dpi in all the antigen groups, but the boosting effect after 35 dpi was explicitly observed in the S1–1, S1–2, and S1–3 groups. Thus, the oral administration of SARS-CoV-2 antigens into mice induced significant humoral and mucosal immune responses. Conclusion This study suggests that L. plantarum is a potential vector that can effectively deliver SARS-CoV-2 epitopes to intestinal mucosal sites and could serve as a novel approach for SARS-CoV-2 mucosal vaccine development.https://doi.org/10.1186/s12934-023-02100-7Lactiplantibacillus plantarumSARS-CoV-2Mucosal delivery vectorOral vaccine |
| spellingShingle | In-Chan Hwang Valerie Diane Valeriano Ji Hoon Song Marcela Pereira Ju Kyoung Oh Kyudong Han Lars Engstrand Dae-Kyung Kang Mucosal immunization with Lactiplantibacillus plantarum-displaying recombinant SARS-CoV-2 epitopes on the surface induces humoral and mucosal immune responses in mice Microbial Cell Factories Lactiplantibacillus plantarum SARS-CoV-2 Mucosal delivery vector Oral vaccine |
| title | Mucosal immunization with Lactiplantibacillus plantarum-displaying recombinant SARS-CoV-2 epitopes on the surface induces humoral and mucosal immune responses in mice |
| title_full | Mucosal immunization with Lactiplantibacillus plantarum-displaying recombinant SARS-CoV-2 epitopes on the surface induces humoral and mucosal immune responses in mice |
| title_fullStr | Mucosal immunization with Lactiplantibacillus plantarum-displaying recombinant SARS-CoV-2 epitopes on the surface induces humoral and mucosal immune responses in mice |
| title_full_unstemmed | Mucosal immunization with Lactiplantibacillus plantarum-displaying recombinant SARS-CoV-2 epitopes on the surface induces humoral and mucosal immune responses in mice |
| title_short | Mucosal immunization with Lactiplantibacillus plantarum-displaying recombinant SARS-CoV-2 epitopes on the surface induces humoral and mucosal immune responses in mice |
| title_sort | mucosal immunization with lactiplantibacillus plantarum displaying recombinant sars cov 2 epitopes on the surface induces humoral and mucosal immune responses in mice |
| topic | Lactiplantibacillus plantarum SARS-CoV-2 Mucosal delivery vector Oral vaccine |
| url | https://doi.org/10.1186/s12934-023-02100-7 |
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