Nanoscale Peptide Self-assemblies Boost BCG-primed Cellular Immunity Against Mycobacterium tuberculosis
Abstract Bacillus Calmette-Guerin (BCG) is the only vaccine against TB and has limited protection efficacy, which wanes past adolescence. Multifunctional CD8+ T cells (IFN-γ+/TNF-α+/IL-2+) are associated with lower reactivation risk and enhanced control of active Mtb infection. Since boosting with B...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2018-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-018-31089-y |
| _version_ | 1818345628776792064 |
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| author | Charles B. Chesson Matthew Huante Rebecca J. Nusbaum Aida G. Walker Tara M. Clover Jagannath Chinnaswamy Janice J. Endsley Jai S. Rudra |
| author_facet | Charles B. Chesson Matthew Huante Rebecca J. Nusbaum Aida G. Walker Tara M. Clover Jagannath Chinnaswamy Janice J. Endsley Jai S. Rudra |
| author_sort | Charles B. Chesson |
| collection | DOAJ |
| description | Abstract Bacillus Calmette-Guerin (BCG) is the only vaccine against TB and has limited protection efficacy, which wanes past adolescence. Multifunctional CD8+ T cells (IFN-γ+/TNF-α+/IL-2+) are associated with lower reactivation risk and enhanced control of active Mtb infection. Since boosting with BCG is contraindicated, booster vaccines that augment T cell immunity in the lungs of BCG-vaccinated individuals are urgently needed. We developed a vaccination strategy based on self-assembling peptide nanofibers presenting Mtb-specific CD8+ or CD4+ T cell epitopes that induce high frequency and antigen-specific effector memory T cells producing IFN-γ and IL-2. Intranasal immunization with peptide nanofibers was well tolerated in mice leading to increased antigen-specific CD8+ T cell population in the lungs. Co-assembled nanofibers of CD8+ T cell epitopes and toll-like receptor 2 (TLR2) agonists induced a 8-fold expansion in multifunctional CD8+ T cell populations in the lungs of vaccinated mice. Aerosol challenge with Mtb in BCG-primed and nanofiber-boosted mice provided an additional 0.5-log CFU reduction in lung bacterial load and indicating enhanced protection compared to BCG alone. Together, these data suggest that heterologous prime-boost with BCG and peptide nanofiber vaccines induces cell mediated immunity in the lung, reduces bacterial burden, and is a potentially safer alternative for boosting BCG-primed immunity. |
| first_indexed | 2024-12-13T17:05:24Z |
| format | Article |
| id | doaj.art-5703a72574d74332afa1078b39195189 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-13T17:05:24Z |
| publishDate | 2018-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5703a72574d74332afa1078b391951892022-12-21T23:37:42ZengNature PortfolioScientific Reports2045-23222018-08-018111410.1038/s41598-018-31089-yNanoscale Peptide Self-assemblies Boost BCG-primed Cellular Immunity Against Mycobacterium tuberculosisCharles B. Chesson0Matthew Huante1Rebecca J. Nusbaum2Aida G. Walker3Tara M. Clover4Jagannath Chinnaswamy5Janice J. Endsley6Jai S. Rudra7Department of Surgical Oncology, Rutgers Cancer Institute of New JerseyDepartment of Microbiology and Immunology, University of Texas Medical BranchDepartment of Pathology, School of Dental Medicine, University of PennsylvaniaDepartment of Microbiology and Immunology, University of Texas Medical BranchDepartment of Pharmacology and Toxicology, University of Texas Medical BranchDepartment of Pathology and Laboratory Medicine, McGovern Medical School, University of Texas Health Science Center at HoustonDepartment of Microbiology and Immunology, University of Texas Medical BranchDepartment of Pharmacology and Toxicology, University of Texas Medical BranchAbstract Bacillus Calmette-Guerin (BCG) is the only vaccine against TB and has limited protection efficacy, which wanes past adolescence. Multifunctional CD8+ T cells (IFN-γ+/TNF-α+/IL-2+) are associated with lower reactivation risk and enhanced control of active Mtb infection. Since boosting with BCG is contraindicated, booster vaccines that augment T cell immunity in the lungs of BCG-vaccinated individuals are urgently needed. We developed a vaccination strategy based on self-assembling peptide nanofibers presenting Mtb-specific CD8+ or CD4+ T cell epitopes that induce high frequency and antigen-specific effector memory T cells producing IFN-γ and IL-2. Intranasal immunization with peptide nanofibers was well tolerated in mice leading to increased antigen-specific CD8+ T cell population in the lungs. Co-assembled nanofibers of CD8+ T cell epitopes and toll-like receptor 2 (TLR2) agonists induced a 8-fold expansion in multifunctional CD8+ T cell populations in the lungs of vaccinated mice. Aerosol challenge with Mtb in BCG-primed and nanofiber-boosted mice provided an additional 0.5-log CFU reduction in lung bacterial load and indicating enhanced protection compared to BCG alone. Together, these data suggest that heterologous prime-boost with BCG and peptide nanofiber vaccines induces cell mediated immunity in the lung, reduces bacterial burden, and is a potentially safer alternative for boosting BCG-primed immunity.https://doi.org/10.1038/s41598-018-31089-y |
| spellingShingle | Charles B. Chesson Matthew Huante Rebecca J. Nusbaum Aida G. Walker Tara M. Clover Jagannath Chinnaswamy Janice J. Endsley Jai S. Rudra Nanoscale Peptide Self-assemblies Boost BCG-primed Cellular Immunity Against Mycobacterium tuberculosis Scientific Reports |
| title | Nanoscale Peptide Self-assemblies Boost BCG-primed Cellular Immunity Against Mycobacterium tuberculosis |
| title_full | Nanoscale Peptide Self-assemblies Boost BCG-primed Cellular Immunity Against Mycobacterium tuberculosis |
| title_fullStr | Nanoscale Peptide Self-assemblies Boost BCG-primed Cellular Immunity Against Mycobacterium tuberculosis |
| title_full_unstemmed | Nanoscale Peptide Self-assemblies Boost BCG-primed Cellular Immunity Against Mycobacterium tuberculosis |
| title_short | Nanoscale Peptide Self-assemblies Boost BCG-primed Cellular Immunity Against Mycobacterium tuberculosis |
| title_sort | nanoscale peptide self assemblies boost bcg primed cellular immunity against mycobacterium tuberculosis |
| url | https://doi.org/10.1038/s41598-018-31089-y |
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