title: Mucosal vaccination with attenuated Mycobacterium tuberculosis induces strong central memory responses and protects against tuberculosis.
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.
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana 70433, USA.|Department of Microbiology and Immunology, Tulane Health Sciences Center, New Orleans, Louisiana 70112, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Kaushal
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana 70433, USA.|Biomedical Sciences Graduate Program, Tulane Health Sciences Center, New Orleans, Louisiana 70112, USA.
authors.forename: Taylor W
authors.initials: TW
authors.lastname: Foreman
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana 70433, USA.
authors.forename: Uma S
authors.initials: US
authors.lastname: Gautam
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana 70433, USA.
authors.forename: Xavier
authors.initials: X
authors.lastname: Alvarez
authors.affiliation: Yerkes National Primate Research Center, Atlanta, Georgia 30329, USA.|Emory Vaccine Center, Atlanta, Georgia 30329, USA.
authors.forename: Toidi
authors.initials: T
authors.lastname: Adekambi
authors.affiliation: University of Rochester Medical Center, Rochester, New York 14642, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Rangel-Moreno
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana 70433, USA.
authors.forename: Nadia A
authors.initials: NA
authors.lastname: Golden
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana 70433, USA.
authors.forename: Ann-Marie F
authors.initials: AM
authors.lastname: Johnson
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana 70433, USA.|Biomedical Sciences Graduate Program, Tulane Health Sciences Center, New Orleans, Louisiana 70112, USA.
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Phillips
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana 70433, USA.
authors.forename: Muhammad H
authors.initials: MH
authors.lastname: Ahsan
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana 70433, USA.
authors.forename: Kasi E
authors.initials: KE
authors.lastname: Russell-Lodrigue
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana 70433, USA.
authors.forename: Lara A
authors.initials: LA
authors.lastname: Doyle
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana 70433, USA.
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Roy
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana 70433, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Didier
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana 70433, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Blanchard
authors.affiliation: Yerkes National Primate Research Center, Atlanta, Georgia 30329, USA.|Emory Vaccine Center, Atlanta, Georgia 30329, USA.
authors.forename: Jyothi
authors.initials: J
authors.lastname: Rengarajan
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana 70433, USA.|Department of Microbiology and Immunology, Tulane Health Sciences Center, New Orleans, Louisiana 70112, USA.|Department of Pathology, Tulane Health Sciences Center, New Orleans, Louisiana 70112, USA.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Lackner
authors.affiliation: Department of Molecular Microbiology, Washington University at St Louis, St Louis, Missouri 63110, USA.
authors.forename: Shabaana A
authors.initials: SA
authors.lastname: Khader
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana 70433, USA.|Center for Biomedical Research Excellence, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana 70803, USA.|Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana 70803, USA.
authors.forename: Smriti
authors.initials: S
authors.lastname: Mehra
mesh_terms: D000336:Aerosols; D000818:Animals; D001500:BCG Vaccine; D001426:Bacterial Proteins / Q000276:immunology*; D018893:Bronchoalveolar Lavage; D007156:Immunologic Memory / Q000187:drug effects*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008221:Lymphoid Tissue / Q000187:drug effects; D008253:Macaca mulatta; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D012808:Sigma Factor / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects*; D014376:Tuberculosis / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000494:pharmacology*; D014611:Vaccination / Q000379:methods
chemical_list: D000336:Aerosols; D001500:BCG Vaccine; D001426:Bacterial Proteins; C120328:SigH protein, bacteria; D012808:Sigma Factor; D032581:Tuberculosis Vaccines