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

• Type of Material: Article
• Authors: Deepak Kaushal, Tulane Health Sciences Center; Taylor W. Foreman, Tulane Health Sciences Center; Uma S. Gautam, Tulane Health Sciences Center; Xavier Alvarez, Tulane Health Sciences Center; Toidi Adekambi, Emory University; Javier Rangel-Moreno, University of Rochester; Nadia A. Golden, Tulane Health Sciences Center; Ann-Marie F. Johnson, Tulane Health Sciences Center; Bonnie L. Phillips, Tulane Health Sciences Center; Muhammad H. Ahsan, Tulane Health Sciences Center; Kasi E. Russell-Lodrigue, Tulane Health Sciences Center; Lara A. Doyle, Tulane Health Sciences Center; Chad J. Roy, Tulane Health Sciences Center; Peter J. Didier, Tulane Health Sciences Center; James L. Blanchard, Tulane Health Sciences Center; Jyothi Rengarajan, Emory University; Andrew A. Lackner, Tulane Natl Primate Res Ctr; Shabaana A. Khader, Washington University; Smriti Mehra, Tulane Health Sciences Center
• Language: English
• Date: 2015-10-01
• Publisher: Nature Publishing Group: Nature Communications
• Publication Version: Final Published Version
• Copyright Statement: © 2015 Macmillan Publishers Limited. All rights reserved.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/ncomms9533
• Title of Journal or Parent Work: Nature Communications
• ISSN: 2041-1723
• Volume: 6
• Start Page: 8533
• End Page: 8533
• Grant/Funding Information: This research was supported by startup funds and a Center for Biomedical Research Excellence (COBRE) award to S.M. (P30GM110760), awards to D.K. (AI089323, HL106790, HL106790-S1, AI111943 and RR026006), S.A.K. and D.K. (AI111914) and the TNPRC (OD011104 and AI058609), including its pilot programme, the Emory Center for AIDS Research (CFAR; AI050409), the Louisiana Board of Regents and the Tulane Office of the Vice-President for Research.
• Keywords: Science & Technology - Other Topics; SIMIAN IMMUNODEFICIENCY VIRUS; T-CELL MEMORY; CYNOMOLGUS MACAQUES; RHESUS MACAQUES; Multidisciplinary Sciences; FACTOR SIGMA(H); LATENT TUBERCULOSIS; CALMETTE-GUERIN; NONHUMAN-PRIMATES; PULMONARY TUBERCULOSIS; AEROSOL VACCINATION; Science & Technology
• Research Categories: Health Sciences, Immunology; Biology, Microbiology

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.