Recombinant BCG to Enhance Its Immunomodulatory Activities
The bacillus Calmette–Guérin (BCG) is an attenuated <i>Mycobacterium bovis</i> derivative that has been widely used as a live vaccine against tuberculosis for a century. In addition to its use as a tuberculosis vaccine, BCG has also been found to have utility in the prevention or treatme...
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| Format: | Article |
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MDPI AG
2022-05-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/10/5/827 |
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| author | Magdalena Kowalewicz-Kulbat Camille Locht |
| author_facet | Magdalena Kowalewicz-Kulbat Camille Locht |
| author_sort | Magdalena Kowalewicz-Kulbat |
| collection | DOAJ |
| description | The bacillus Calmette–Guérin (BCG) is an attenuated <i>Mycobacterium bovis</i> derivative that has been widely used as a live vaccine against tuberculosis for a century. In addition to its use as a tuberculosis vaccine, BCG has also been found to have utility in the prevention or treatment of unrelated diseases, including cancer. However, the protective and therapeutic efficacy of BCG against tuberculosis and other diseases is not perfect. For three decades, it has been possible to genetically modify BCG in an attempt to improve its efficacy. Various immune-modulatory molecules have been produced in recombinant BCG strains and tested for protection against tuberculosis or treatment of several cancers or inflammatory diseases. These molecules include cytokines, bacterial toxins or toxin fragments, as well as other protein and non-protein immune-modulatory molecules. The deletion of genes responsible for the immune-suppressive properties of BCG has also been explored for their effect on BCG-induced innate and adaptive immune responses. Most studies limited their investigations to the description of T cell immune responses that were modified by the genetic modifications of BCG. Some studies also reported improved protection by recombinant BCG against tuberculosis or enhanced therapeutic efficacy against various cancer forms or allergies. However, so far, these investigations have been limited to mouse models, and the prophylactic or therapeutic potential of recombinant BCG strains has not yet been illustrated in other species, including humans, with the exception of a genetically modified BCG strain that is now in late-stage clinical development as a vaccine against tuberculosis. In this review, we provide an overview of the different molecular engineering strategies adopted over the last three decades in order to enhance the immune-modulatory potential of BCG. |
| first_indexed | 2024-03-10T01:38:17Z |
| format | Article |
| id | doaj.art-469b632663174d03acd08c831eae3d8e |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T01:38:17Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-469b632663174d03acd08c831eae3d8e2023-11-23T13:27:55ZengMDPI AGVaccines2076-393X2022-05-0110582710.3390/vaccines10050827Recombinant BCG to Enhance Its Immunomodulatory ActivitiesMagdalena Kowalewicz-Kulbat0Camille Locht1Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, PolandDepartment of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, PolandThe bacillus Calmette–Guérin (BCG) is an attenuated <i>Mycobacterium bovis</i> derivative that has been widely used as a live vaccine against tuberculosis for a century. In addition to its use as a tuberculosis vaccine, BCG has also been found to have utility in the prevention or treatment of unrelated diseases, including cancer. However, the protective and therapeutic efficacy of BCG against tuberculosis and other diseases is not perfect. For three decades, it has been possible to genetically modify BCG in an attempt to improve its efficacy. Various immune-modulatory molecules have been produced in recombinant BCG strains and tested for protection against tuberculosis or treatment of several cancers or inflammatory diseases. These molecules include cytokines, bacterial toxins or toxin fragments, as well as other protein and non-protein immune-modulatory molecules. The deletion of genes responsible for the immune-suppressive properties of BCG has also been explored for their effect on BCG-induced innate and adaptive immune responses. Most studies limited their investigations to the description of T cell immune responses that were modified by the genetic modifications of BCG. Some studies also reported improved protection by recombinant BCG against tuberculosis or enhanced therapeutic efficacy against various cancer forms or allergies. However, so far, these investigations have been limited to mouse models, and the prophylactic or therapeutic potential of recombinant BCG strains has not yet been illustrated in other species, including humans, with the exception of a genetically modified BCG strain that is now in late-stage clinical development as a vaccine against tuberculosis. In this review, we provide an overview of the different molecular engineering strategies adopted over the last three decades in order to enhance the immune-modulatory potential of BCG.https://www.mdpi.com/2076-393X/10/5/827rBCGcytokinestuberculosisbacterial toxinsnon-tuberculosis diseases |
| spellingShingle | Magdalena Kowalewicz-Kulbat Camille Locht Recombinant BCG to Enhance Its Immunomodulatory Activities Vaccines rBCG cytokines tuberculosis bacterial toxins non-tuberculosis diseases |
| title | Recombinant BCG to Enhance Its Immunomodulatory Activities |
| title_full | Recombinant BCG to Enhance Its Immunomodulatory Activities |
| title_fullStr | Recombinant BCG to Enhance Its Immunomodulatory Activities |
| title_full_unstemmed | Recombinant BCG to Enhance Its Immunomodulatory Activities |
| title_short | Recombinant BCG to Enhance Its Immunomodulatory Activities |
| title_sort | recombinant bcg to enhance its immunomodulatory activities |
| topic | rBCG cytokines tuberculosis bacterial toxins non-tuberculosis diseases |
| url | https://www.mdpi.com/2076-393X/10/5/827 |
| work_keys_str_mv | AT magdalenakowalewiczkulbat recombinantbcgtoenhanceitsimmunomodulatoryactivities AT camillelocht recombinantbcgtoenhanceitsimmunomodulatoryactivities |