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Nat Commun. 2015 Oct 13;6:8533. doi: 10.1038/ncomms9533.

Mucosal vaccination with attenuated Mycobacterium tuberculosis induces strong central memory responses and protects against tuberculosis.

Author information

1
Tulane National Primate Research Center, Covington, Louisiana 70433, USA.
2
Department of Microbiology and Immunology, Tulane Health Sciences Center, New Orleans, Louisiana 70112, USA.
3
Biomedical Sciences Graduate Program, Tulane Health Sciences Center, New Orleans, Louisiana 70112, USA.
4
Yerkes National Primate Research Center, Atlanta, Georgia 30329, USA.
5
Emory Vaccine Center, Atlanta, Georgia 30329, USA.
6
University of Rochester Medical Center, Rochester, New York 14642, USA.
7
Department of Pathology, Tulane Health Sciences Center, New Orleans, Louisiana 70112, USA.
8
Department of Molecular Microbiology, Washington University at St Louis, St Louis, Missouri 63110, USA.
9
Center for Biomedical Research Excellence, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana 70803, USA.
10
Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana 70803, USA.

Abstract

Tuberculosis (TB) is a global pandaemic, partially due to the failure of vaccination approaches. Novel anti-TB vaccines are therefore urgently required. Here we show that aerosol immunization of macaques with the Mtb mutant in SigH (MtbΔsigH) results in significant recruitment of inducible bronchus-associated lymphoid tissue (iBALT) as well as CD4(+) and CD8(+) T cells expressing activation and proliferation markers to the lungs. Further, the findings indicate that pulmonary vaccination with MtbΔsigH elicited strong central memory CD4(+) and CD8(+) T-cell responses in the lung. Vaccination with MtbΔsigH results in significant protection against a lethal TB challenge, as evidenced by an approximately three log reduction in bacterial burdens, significantly diminished clinical manifestations and granulomatous pathology and characterized by the presence of profound iBALT. This highly protective response is virtually absent in unvaccinated and BCG-vaccinated animals after challenge. These results suggest that future TB vaccine candidates can be developed on the basis of MtbΔsigH.

PMID:
26460802
PMCID:
PMC4608260
DOI:
10.1038/ncomms9533
[Indexed for MEDLINE]
Free PMC Article

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