Department of Medicine
Amino Acids, Peptides, and Proteins | Bacterial Infections and Mycoses | Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Immunotherapy | Microbiology
Development of an effective tuberculosis (TB) vaccine has suffered from an incomplete understanding of the correlates of protection against Mycobacterium tuberculosis (Mtb). However, recent work has shown that compared to standard intradermal Bacille Calmette-Guerin (BCG) vaccination, intravenous (IV) BCG vaccination provides nearly complete protection against TB in rhesus macaques. While studies have focused on cellular immunity in this setting, the antibody response elicited by IV BCG vaccination remains incompletely defined. Using an agnostic antibody profiling approach, here we show that IV BCG drives superior antibody responses in the plasma and the bronchoalveolar lavage fluid (BAL). While IV BCG immunization resulted in the broad expansion of antibody titers and effector functions, surprisingly, IgM titers were among the strongest markers of reduced bacterial burden in the plasma and BAL of BCG immunized animals. Moreover, IgM immunity was also enriched among animals receiving protective vaccination with an attenuated Mtb strain. Finally, a LAM-specific IgM monoclonal antibody reduced Mtb survival in vitro. Collectively, these data highlight the potential importance of IgM responses as a marker and as a functional mediator of protection against TB.
Immunology, tuberculosis, vaccination, antibodies
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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
bioRxiv 2021.05.06.442979; doi: https://doi.org/10.1101/2021.05.06.442979. Link to preprint on bioRxiv.
Irvine EB, Li W, Fortune S, Alter G. (2021). Robust IgM responses following vaccination are associated with prevention of Mycobacterium tuberculosis infection in macaques [preprint]. UMass Chan Medical School Faculty Publications. https://doi.org/10.1101/2021.05.06.442979. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/2040
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