Humoral correlates of protection against Mycobacterium tuberculosis following intravenous BCG vaccination in rhesus macaques
Summary: Altering Bacille Calmette-Guérin (BCG) immunization from low-dose intradermal (i.d.) to high-dose intravenous (i.v.) vaccination provides a high level of protection against Mycobacterium tuberculosis (Mtb). In addition to strong T cell immunity, i.v. BCG drives robust humoral immune respons...
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Elsevier
2024-12-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224023538 |
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| author | Edward B. Irvine Patricia A. Darrah Shu Wang Chuangqi Wang Ryan P. McNamara Mario Roederer Robert A. Seder Douglas A. Lauffenburger JoAnne L. Flynn Sarah M. Fortune Galit Alter |
| author_facet | Edward B. Irvine Patricia A. Darrah Shu Wang Chuangqi Wang Ryan P. McNamara Mario Roederer Robert A. Seder Douglas A. Lauffenburger JoAnne L. Flynn Sarah M. Fortune Galit Alter |
| author_sort | Edward B. Irvine |
| collection | DOAJ |
| description | Summary: Altering Bacille Calmette-Guérin (BCG) immunization from low-dose intradermal (i.d.) to high-dose intravenous (i.v.) vaccination provides a high level of protection against Mycobacterium tuberculosis (Mtb). In addition to strong T cell immunity, i.v. BCG drives robust humoral immune responses that track with bacterial control. However, given the near-complete protection afforded by high-dose i.v. BCG immunization, a precise correlate of protection was difficult to define. Here we leveraged plasma and bronchoalveolar lavage fluid (BAL) from a cohort of rhesus macaques that received decreasing doses of i.v. BCG and aimed to define correlates of immunity following Mtb challenge. We show an i.v. BCG dose-dependent induction of mycobacterial-specific humoral immune responses. Antibody responses at peak immunogenicity predicted bacterial control post-challenge. Multivariate analyses revealed antibody-mediated complement and natural killer (NK) cell-activating humoral networks as key signatures of protective immunity. This work extends our understanding of humoral biomarkers and potential mechanisms of i.v. BCG-mediated protection against Mtb. |
| format | Article |
| id | doaj-art-3a7ffcc85dc94f49b647fd43b83a2e7f |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-3a7ffcc85dc94f49b647fd43b83a2e7f2024-12-22T05:28:39ZengElsevieriScience2589-00422024-12-012712111128Humoral correlates of protection against Mycobacterium tuberculosis following intravenous BCG vaccination in rhesus macaquesEdward B. Irvine0Patricia A. Darrah1Shu Wang2Chuangqi Wang3Ryan P. McNamara4Mario Roederer5Robert A. Seder6Douglas A. Lauffenburger7JoAnne L. Flynn8Sarah M. Fortune9Galit Alter10Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD 20892, USADepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USADepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USARagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD 20892, USAVaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD 20892, USADepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USADepartment of Microbiology and Molecular Genetics and Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USARagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Corresponding authorRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Corresponding authorSummary: Altering Bacille Calmette-Guérin (BCG) immunization from low-dose intradermal (i.d.) to high-dose intravenous (i.v.) vaccination provides a high level of protection against Mycobacterium tuberculosis (Mtb). In addition to strong T cell immunity, i.v. BCG drives robust humoral immune responses that track with bacterial control. However, given the near-complete protection afforded by high-dose i.v. BCG immunization, a precise correlate of protection was difficult to define. Here we leveraged plasma and bronchoalveolar lavage fluid (BAL) from a cohort of rhesus macaques that received decreasing doses of i.v. BCG and aimed to define correlates of immunity following Mtb challenge. We show an i.v. BCG dose-dependent induction of mycobacterial-specific humoral immune responses. Antibody responses at peak immunogenicity predicted bacterial control post-challenge. Multivariate analyses revealed antibody-mediated complement and natural killer (NK) cell-activating humoral networks as key signatures of protective immunity. This work extends our understanding of humoral biomarkers and potential mechanisms of i.v. BCG-mediated protection against Mtb.http://www.sciencedirect.com/science/article/pii/S2589004224023538Health sciencesImmunologyPathophysiology |
| spellingShingle | Edward B. Irvine Patricia A. Darrah Shu Wang Chuangqi Wang Ryan P. McNamara Mario Roederer Robert A. Seder Douglas A. Lauffenburger JoAnne L. Flynn Sarah M. Fortune Galit Alter Humoral correlates of protection against Mycobacterium tuberculosis following intravenous BCG vaccination in rhesus macaques iScience Health sciences Immunology Pathophysiology |
| title | Humoral correlates of protection against Mycobacterium tuberculosis following intravenous BCG vaccination in rhesus macaques |
| title_full | Humoral correlates of protection against Mycobacterium tuberculosis following intravenous BCG vaccination in rhesus macaques |
| title_fullStr | Humoral correlates of protection against Mycobacterium tuberculosis following intravenous BCG vaccination in rhesus macaques |
| title_full_unstemmed | Humoral correlates of protection against Mycobacterium tuberculosis following intravenous BCG vaccination in rhesus macaques |
| title_short | Humoral correlates of protection against Mycobacterium tuberculosis following intravenous BCG vaccination in rhesus macaques |
| title_sort | humoral correlates of protection against mycobacterium tuberculosis following intravenous bcg vaccination in rhesus macaques |
| topic | Health sciences Immunology Pathophysiology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224023538 |
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