Robust IgM responses following vaccination are associated with prevention of<i>Mycobacterium tuberculosis</i>infection in macaques
Abstract Development of an effective tuberculosis (TB) vaccine has suffered from an incomplete understanding of the correlates of protection againstMycobacterium 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 expansion of a robust IgM, IgG, IgA, Fc-receptor binding antibodies, and antibody effector functions in the BAL, 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 attenuatedMtbstrain. Finally, a LAM-specific IgM monoclonal antibody reducedMtbsurvivalin vitro. Collectively, these data highlight the potential importance of IgM responses as a marker and as a functional mediator of protection against TB..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 03. Nov. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Irvine, Edward B. [VerfasserIn] |
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| doi: |
10.1101/2021.05.06.442979 |
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| PPN (Katalog-ID): |
XBI020512376 |
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| 245 | 1 | 0 | |a Robust IgM responses following vaccination are associated with prevention of<i>Mycobacterium tuberculosis</i>infection in macaques |
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| 520 | |a Abstract Development of an effective tuberculosis (TB) vaccine has suffered from an incomplete understanding of the correlates of protection againstMycobacterium 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 expansion of a robust IgM, IgG, IgA, Fc-receptor binding antibodies, and antibody effector functions in the BAL, 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 attenuatedMtbstrain. Finally, a LAM-specific IgM monoclonal antibody reducedMtbsurvivalin vitro. Collectively, these data highlight the potential importance of IgM responses as a marker and as a functional mediator of protection against TB. | ||
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| 700 | 1 | |a Darrah, Patricia A. |4 aut | |
| 700 | 1 | |a Shin, Sally |4 aut | |
| 700 | 1 | |a Choudhary, Alok |4 aut | |
| 700 | 1 | |a Li, Wenjun |4 aut | |
| 700 | 1 | |a Honnen, William |4 aut | |
| 700 | 1 | |a Mehra, Smriti |4 aut | |
| 700 | 1 | |a Kaushal, Deepak |4 aut | |
| 700 | 1 | |a Gideon, Hannah Priyadarshini |4 aut | |
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| 700 | 1 | |a Alter, Galit |4 aut | |
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