Robust IgM responses following intravenous vaccination with Bacille Calmette–Guérin associate with prevention of Mycobacterium tuberculosis infection in macaques
Autor: | Patricia A. Darrah, Sally Shin, Robert A. Seder, Galit Alter, Deepak Kaushal, Smriti Mehra, Hannah P. Gideon, Anthony O’Neil, Abraham Pinter, JoAnne L. Flynn, Sarah M. Fortune, Mario Roederer, Edward B. Irvine, Wenjun Li, William J. Honnen, Alok Choudhary |
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Rok vydání: | 2021 |
Předmět: |
Time Factors
Tuberculosis Immunology Mycobacterium tuberculosis Immunogenicity Vaccine medicine Animals Immunology and Allergy biology medicine.diagnostic_test business.industry Vaccination Antibody titer respiratory system medicine.disease biology.organism_classification Antibodies Bacterial Macaca mulatta In vitro Disease Models Animal Titer Bronchoalveolar lavage Immunoglobulin M Host-Pathogen Interactions BCG Vaccine biology.protein Administration Intravenous Antibody business Biomarkers |
Zdroj: | Nature Immunology. 22:1515-1523 |
ISSN: | 1529-2916 1529-2908 |
Popis: | Development of an effective tuberculosis (TB) vaccine has suffered from an incomplete understanding of the correlates of protection against Mycobacterium tuberculosis (Mtb). Intravenous (i.v.) vaccination with Bacille Calmette–Guerin (BCG) provides nearly complete protection against TB in rhesus macaques, but the antibody response it elicits remains incompletely defined. Here we show that i.v. BCG drives superior antibody responses in the plasma and the lungs of rhesus macaques compared to traditional intradermal BCG administration. While i.v. BCG broadly expands antibody titers and functions, IgM titers in the plasma and lungs of immunized macaques are among the strongest markers of reduced bacterial burden. IgM was also enriched in macaques that received protective vaccination with an attenuated strain of Mtb. Finally, an Mtb-specific IgM monoclonal antibody reduced Mtb survival in vitro. Collectively, these data highlight the potential importance of IgM responses as a marker and mediator of protection against TB. Alter and colleagues show that IgM titers in the plasma and bronchoalveolar lavage fluid represent markers of reduced Mtb burden in rhesus macaques vaccinated intravenously with Bacille Calmette–Guerin. |
Databáze: | OpenAIRE |
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