BCG-induced trained immunity enhances acellular pertussis vaccination responses in an explorative randomized clinical trial
Abstract Acellular pertussis (aP) booster vaccines are central to pertussis immunization programs, although their effectiveness varies. The Bacille Calmette-Guérin (BCG) vaccine is a prototype inducer of trained immunity, which enhances immune responses to subsequent infections or vaccinations. Whil...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-02-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-022-00438-4 |
| _version_ | 1797425101113655296 |
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| author | Joshua Gillard Bastiaan A. Blok Daniel R. Garza Prashanna Balaji Venkatasubramanian Elles Simonetti Marc J. Eleveld Guy A. M. Berbers Pieter G. M. van Gageldonk Irma Joosten Ronald de Groot L. Charlotte J. de Bree Reinout van Crevel Marien I. de Jonge Martijn A. Huynen Mihai G. Netea Dimitri A. Diavatopoulos |
| author_facet | Joshua Gillard Bastiaan A. Blok Daniel R. Garza Prashanna Balaji Venkatasubramanian Elles Simonetti Marc J. Eleveld Guy A. M. Berbers Pieter G. M. van Gageldonk Irma Joosten Ronald de Groot L. Charlotte J. de Bree Reinout van Crevel Marien I. de Jonge Martijn A. Huynen Mihai G. Netea Dimitri A. Diavatopoulos |
| author_sort | Joshua Gillard |
| collection | DOAJ |
| description | Abstract Acellular pertussis (aP) booster vaccines are central to pertussis immunization programs, although their effectiveness varies. The Bacille Calmette-Guérin (BCG) vaccine is a prototype inducer of trained immunity, which enhances immune responses to subsequent infections or vaccinations. While previous clinical studies have demonstrated that trained immunity can protect against heterologous infections, its effect on aP vaccines in humans is unknown. We conducted a clinical study in order to determine the immunological effects of trained immunity on pertussis vaccination. Healthy female volunteers were randomly assigned to either receive BCG followed by a booster dose of tetanus-diphteria-pertussis inactivated polio vaccine (Tdap-IPV) 3 months later (BCG-trained), BCG + Tdap-IPV concurrently, or Tdap-IPV followed by BCG 3 months later. Primary outcomes were pertussis-specific humoral, T- and B-cell responses and were quantified at baseline of Tdap-IPV vaccination and 2 weeks thereafter. As a secondary outcome in the BCG-trained cohort, ex vivo leukocyte responses were measured in response to unrelated stimuli before and after BCG vaccination. BCG vaccination 3 months prior to, but not concurrent with, Tdap-IPV improves pertussis-specific Th1-cell and humoral responses, and also increases total memory B cell responses. These responses were correlated with enhanced IL-6 and IL-1β production at the baseline of Tdap-IPV vaccination in the BCG-trained cohort. Our study demonstrates that prior BCG vaccination potentiates immune responses to pertussis vaccines and that biomarkers of trained immunity are the most reliable correlates of those responses. |
| first_indexed | 2024-03-09T08:11:08Z |
| format | Article |
| id | doaj.art-03fd26af521743d3bf22ca86c1c84e94 |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-09T08:11:08Z |
| publishDate | 2022-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-03fd26af521743d3bf22ca86c1c84e942023-12-02T23:15:24ZengNature Portfolionpj Vaccines2059-01052022-02-01711910.1038/s41541-022-00438-4BCG-induced trained immunity enhances acellular pertussis vaccination responses in an explorative randomized clinical trialJoshua Gillard0Bastiaan A. Blok1Daniel R. Garza2Prashanna Balaji Venkatasubramanian3Elles Simonetti4Marc J. Eleveld5Guy A. M. Berbers6Pieter G. M. van Gageldonk7Irma Joosten8Ronald de Groot9L. Charlotte J. de Bree10Reinout van Crevel11Marien I. de Jonge12Martijn A. Huynen13Mihai G. Netea14Dimitri A. Diavatopoulos15Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical CenterDepartment of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical CenterCenter for Molecular and Biomolecular Informatics, Radboud University Medical CenterCenter for Molecular and Biomolecular Informatics, Radboud University Medical CenterSection Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical CenterSection Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical CenterCentre for Infectious Disease Control, National Institute of Public Health and the EnvironmentCentre for Infectious Disease Control, National Institute of Public Health and the EnvironmentLaboratory for Medical Immunology, Radboud University Medical CenterSection Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical CenterDepartment of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical CenterDepartment of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical CenterSection Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical CenterCenter for Molecular and Biomolecular Informatics, Radboud University Medical CenterDepartment of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical CenterSection Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical CenterAbstract Acellular pertussis (aP) booster vaccines are central to pertussis immunization programs, although their effectiveness varies. The Bacille Calmette-Guérin (BCG) vaccine is a prototype inducer of trained immunity, which enhances immune responses to subsequent infections or vaccinations. While previous clinical studies have demonstrated that trained immunity can protect against heterologous infections, its effect on aP vaccines in humans is unknown. We conducted a clinical study in order to determine the immunological effects of trained immunity on pertussis vaccination. Healthy female volunteers were randomly assigned to either receive BCG followed by a booster dose of tetanus-diphteria-pertussis inactivated polio vaccine (Tdap-IPV) 3 months later (BCG-trained), BCG + Tdap-IPV concurrently, or Tdap-IPV followed by BCG 3 months later. Primary outcomes were pertussis-specific humoral, T- and B-cell responses and were quantified at baseline of Tdap-IPV vaccination and 2 weeks thereafter. As a secondary outcome in the BCG-trained cohort, ex vivo leukocyte responses were measured in response to unrelated stimuli before and after BCG vaccination. BCG vaccination 3 months prior to, but not concurrent with, Tdap-IPV improves pertussis-specific Th1-cell and humoral responses, and also increases total memory B cell responses. These responses were correlated with enhanced IL-6 and IL-1β production at the baseline of Tdap-IPV vaccination in the BCG-trained cohort. Our study demonstrates that prior BCG vaccination potentiates immune responses to pertussis vaccines and that biomarkers of trained immunity are the most reliable correlates of those responses.https://doi.org/10.1038/s41541-022-00438-4 |
| spellingShingle | Joshua Gillard Bastiaan A. Blok Daniel R. Garza Prashanna Balaji Venkatasubramanian Elles Simonetti Marc J. Eleveld Guy A. M. Berbers Pieter G. M. van Gageldonk Irma Joosten Ronald de Groot L. Charlotte J. de Bree Reinout van Crevel Marien I. de Jonge Martijn A. Huynen Mihai G. Netea Dimitri A. Diavatopoulos BCG-induced trained immunity enhances acellular pertussis vaccination responses in an explorative randomized clinical trial npj Vaccines |
| title | BCG-induced trained immunity enhances acellular pertussis vaccination responses in an explorative randomized clinical trial |
| title_full | BCG-induced trained immunity enhances acellular pertussis vaccination responses in an explorative randomized clinical trial |
| title_fullStr | BCG-induced trained immunity enhances acellular pertussis vaccination responses in an explorative randomized clinical trial |
| title_full_unstemmed | BCG-induced trained immunity enhances acellular pertussis vaccination responses in an explorative randomized clinical trial |
| title_short | BCG-induced trained immunity enhances acellular pertussis vaccination responses in an explorative randomized clinical trial |
| title_sort | bcg induced trained immunity enhances acellular pertussis vaccination responses in an explorative randomized clinical trial |
| url | https://doi.org/10.1038/s41541-022-00438-4 |
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