Self-adjuvanting nanovaccines boost lung-resident CD4+ T cell immune responses in BCG-primed mice
Abstract Heterologous vaccine regimens could extend waning protection in the global population immunized with Mycobacterium bovis Bacille Calmette-Guerin (BCG). We demonstrate that pulmonary delivery of peptide nanofibers (PNFs) bearing an Ag85B CD4+ T cell epitope increased the frequency of antigen...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-04-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-022-00466-0 |
| _version_ | 1827775732549419008 |
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| author | Megan A. Files Kubra F. Naqvi Tais B. Saito Tara M. Clover Jai S. Rudra Janice J. Endsley |
| author_facet | Megan A. Files Kubra F. Naqvi Tais B. Saito Tara M. Clover Jai S. Rudra Janice J. Endsley |
| author_sort | Megan A. Files |
| collection | DOAJ |
| description | Abstract Heterologous vaccine regimens could extend waning protection in the global population immunized with Mycobacterium bovis Bacille Calmette-Guerin (BCG). We demonstrate that pulmonary delivery of peptide nanofibers (PNFs) bearing an Ag85B CD4+ T cell epitope increased the frequency of antigen-specific T cells in BCG-primed mice, including heterogenous populations with tissue resident memory (Trm) and effector memory (Tem) phenotype, and functional cytokine recall. Adoptive transfer of dendritic cells pulsed with Ag85B-bearing PNFs further expanded the frequency and functional repertoire of memory CD4+ T cells. Transcriptomic analysis suggested that the adjuvanticity of peptide nanofibers is, in part, due to the release of damage-associated molecular patterns. A single boost with monovalent Ag85B PNF in BCG-primed mice did not reduce lung bacterial burden compared to BCG alone following aerosol Mtb challenge. These findings support the need for novel BCG booster strategies that activate pools of Trm cells with potentially diverse localization, trafficking, and immune function. |
| first_indexed | 2024-03-11T13:54:16Z |
| format | Article |
| id | doaj.art-74cb267c345f461e8f9ffd236df85864 |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-11T13:54:16Z |
| publishDate | 2022-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-74cb267c345f461e8f9ffd236df858642023-11-02T07:18:06ZengNature Portfolionpj Vaccines2059-01052022-04-017111410.1038/s41541-022-00466-0Self-adjuvanting nanovaccines boost lung-resident CD4+ T cell immune responses in BCG-primed miceMegan A. Files0Kubra F. Naqvi1Tais B. Saito2Tara M. Clover3Jai S. Rudra4Janice J. Endsley5Department of Microbiology and Immunology, University of Texas Medical BranchDepartment of Internal Medicine, University of Texas Southwestern Medical CenterDepartment of Pathology, University of Texas Medical BranchComprehensive Industrial Hygiene Laboratory (CIHL), Navy Environmental and Preventive Medicine Unit TWO (NEPMU-2), Department of the NavyDepartment of Biomedical Engineering, McKelvey School of Engineering, Washington University in St. LouisDepartment of Microbiology and Immunology, University of Texas Medical BranchAbstract Heterologous vaccine regimens could extend waning protection in the global population immunized with Mycobacterium bovis Bacille Calmette-Guerin (BCG). We demonstrate that pulmonary delivery of peptide nanofibers (PNFs) bearing an Ag85B CD4+ T cell epitope increased the frequency of antigen-specific T cells in BCG-primed mice, including heterogenous populations with tissue resident memory (Trm) and effector memory (Tem) phenotype, and functional cytokine recall. Adoptive transfer of dendritic cells pulsed with Ag85B-bearing PNFs further expanded the frequency and functional repertoire of memory CD4+ T cells. Transcriptomic analysis suggested that the adjuvanticity of peptide nanofibers is, in part, due to the release of damage-associated molecular patterns. A single boost with monovalent Ag85B PNF in BCG-primed mice did not reduce lung bacterial burden compared to BCG alone following aerosol Mtb challenge. These findings support the need for novel BCG booster strategies that activate pools of Trm cells with potentially diverse localization, trafficking, and immune function.https://doi.org/10.1038/s41541-022-00466-0 |
| spellingShingle | Megan A. Files Kubra F. Naqvi Tais B. Saito Tara M. Clover Jai S. Rudra Janice J. Endsley Self-adjuvanting nanovaccines boost lung-resident CD4+ T cell immune responses in BCG-primed mice npj Vaccines |
| title | Self-adjuvanting nanovaccines boost lung-resident CD4+ T cell immune responses in BCG-primed mice |
| title_full | Self-adjuvanting nanovaccines boost lung-resident CD4+ T cell immune responses in BCG-primed mice |
| title_fullStr | Self-adjuvanting nanovaccines boost lung-resident CD4+ T cell immune responses in BCG-primed mice |
| title_full_unstemmed | Self-adjuvanting nanovaccines boost lung-resident CD4+ T cell immune responses in BCG-primed mice |
| title_short | Self-adjuvanting nanovaccines boost lung-resident CD4+ T cell immune responses in BCG-primed mice |
| title_sort | self adjuvanting nanovaccines boost lung resident cd4 t cell immune responses in bcg primed mice |
| url | https://doi.org/10.1038/s41541-022-00466-0 |
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