Abstract
Mycobacterium tuberculosis remains a threat to global health, and a more efficacious vaccine is needed to prevent disease caused by M. tuberculosis. We previously reported that the mycobacterial ribosome is a major target of CD4 + T cells in mice immunized with a genetically modified Mycobacterium smegmatis strain (IKEPLUS) but not in mice immunized with Mycobacterium bovis BCG. Two specific ribosomal proteins, RplJ and RpsA, were identified as cross-reactive targets of M. tuberculosis, but the breadth of the CD4 + T cell response to M. tuberculosis ribosomes was not determined. In the present study, a library of M. tuberculosis ribosomal proteins and in silico-predicted peptide libraries were used to screen CD4 + T cell responses in IKEPLUS-immunized mice. This identified 24 out of 57 M. tuberculosis ribosomal proteins distributed over both large and small ribosome subunits as specific CD4 + T cell targets. Although BCG did not induce detectable responses against ribosomal proteins or peptide epitopes, the M. tuberculosis ribosomal protein RplJ produced a robust and multifunctional Th1-like CD4 + T cell population when administered as a booster vaccine to previously BCG-primed mice. Boosting of BCGprimed immunity with the M. tuberculosis RplJ protein led to significantly reduced lung pathology compared to that in BCG-immunized animals and reductions in the bacterial burdens in the mediastinal lymph node compared to those in naive and standard BCG-vaccinated mice. These results identify the mycobacterial ribosome as a potential source of cryptic or subdominant antigenic targets of protective CD4 + T cell responses and suggest that supplementing BCG with ribosomal antigens may enhance protective vaccination against M. tuberculosis.
Original language | English (US) |
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Article number | e00009-18 |
Journal | Infection and immunity |
Volume | 86 |
Issue number | 9 |
DOIs | |
State | Published - Sep 1 2018 |
Keywords
- Antigen
- Cryptic
- Mycobacteriology
- Ribosome
- T cells
- Tuberculosis
- Tuberculosis vaccines
ASJC Scopus subject areas
- Parasitology
- Microbiology
- Immunology
- Infectious Diseases