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

Deepak Kaushal (), Taylor W. Foreman, Uma S. Gautam, Xavier Alvarez, Toidi Adekambi, Javier Rangel-Moreno, Nadia A. Golden, Ann-Marie F. Johnson, Bonnie L. Phillips, Muhammad H. Ahsan, Kasi E. Russell-Lodrigue, Lara A. Doyle, Chad J. Roy, Peter J. Didier, James L. Blanchard, Jyothi Rengarajan, Andrew A. Lackner, Shabaana A. Khader and Smriti Mehra ()
Additional contact information
Deepak Kaushal: Tulane National Primate Research Center
Taylor W. Foreman: Tulane National Primate Research Center
Uma S. Gautam: Tulane National Primate Research Center
Xavier Alvarez: Tulane National Primate Research Center
Toidi Adekambi: Yerkes National Primate Research Center
Javier Rangel-Moreno: University of Rochester Medical Center
Nadia A. Golden: Tulane National Primate Research Center
Ann-Marie F. Johnson: Tulane National Primate Research Center
Bonnie L. Phillips: Tulane National Primate Research Center
Muhammad H. Ahsan: Tulane National Primate Research Center
Kasi E. Russell-Lodrigue: Tulane National Primate Research Center
Lara A. Doyle: Tulane National Primate Research Center
Chad J. Roy: Tulane National Primate Research Center
Peter J. Didier: Tulane National Primate Research Center
James L. Blanchard: Tulane National Primate Research Center
Jyothi Rengarajan: Yerkes National Primate Research Center
Andrew A. Lackner: Tulane National Primate Research Center
Shabaana A. Khader: Washington University at St Louis
Smriti Mehra: Tulane National Primate Research Center

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9533

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