Robust IgM responses following intravenous vaccination with Bacille Calmette–Guérin associate with prevention of Mycobacterium tuberculosis infection in macaques
Abstract
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–Guérin (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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 22, 2021
- Source ID
- 10.1038/s41590-021-01066-1
Entities
People
- Abraham Pinter
- Alok Choudhary
- Anthony O’neil
- Deepak Kaushal
- Edward B. Irvine
- Galit Alter
- Hannah Priyadarshini Gideon
- JoAnne Flynn
- Mario Roederer
- Patricia A Darrah
- Robert A Seder
- Sally Shin
- Sarah Fortune
- Smriti Mehra
- Wenjun Li
- William Honnen
Organizations
- Gates Foundation
- National Institutes of Health
- United States Department of Defense