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Nanoparticle Vaccines Against Infectious Diseases

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Front. Immunol. | doi: 10.3389/fimmu.2018.00346

Mucosal Delivery of Fusion Proteins with Bacillus subtilis Spores Enhances Protection against Tuberculosis by BCG

  • 1St George's, University of London, United Kingdom
  • 2Lionex (Germany), Germany
  • 3Royal Holloway, University of London, United Kingdom

Tuberculosis (TB) is the most deadly infectious disease in existence, and the only available vaccine, Bacillus Calmette-Guérin (BCG), is almost a century old and poorly protective. The immunological complexity of TB, coupled with rising resistance to antimicrobial therapies, necessitates a pipeline of diverse novel vaccines. Here, we show that B. subtilis spores can be coated with a fusion protein (‘FP1’) consisting of M. tuberculosis (Mtb) antigens Ag85B, ACR and HBHA. The resultant vaccine, Spore-FP1, was tested in a murine low-dose Mtb aerosol challenge model. Mice were primed with subcutaneous BCG, followed by mucosal booster immunisations with Spore-FP1. We show that Spore-FP1 enhanced pulmonary control of Mtb, as evidenced by reduced bacterial burdens in the lungs. This was associated with elevated antigen-specific IgG and IgA titres in the serum and lung mucosal surface, respectively. Spore-FP1 immunisation generated superior antigen-specific memory T-cell proliferation in both CD4+ and CD8+ compartments, alongside bolstered Th1-, Th17- and Treg-type cytokine production, compared to BCG immunisation alone. CD69+CD103+ tissue resident memory T-cells (Trm) were found within the lung parenchyma after mucosal immunisation with Spore-FP1, confirming the advantages of mucosal delivery. Our data show that Spore-FP1 is a promising new TB vaccine that can successfully augment protection and immunogenicity in BCG-primed animals.

Keywords: Tuberculosis, Vaccine, mucosal, Spores, Immunity, Cellular

Received: 13 Nov 2017; Accepted: 07 Feb 2018.

Edited by:

Jeffrey K. Actor, University of Texas Health Science Center at Houston, United States

Reviewed by:

Camille Locht, Inserm, France
Owen Kavanagh, York St John University, United Kingdom  

Copyright: © 2018 Copland, Hart, Diogo, Harris, Paul, Singh, Cutting and Reljic. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Rajko Reljic, St George's, University of London, London, United Kingdom, rreljic@sgul.ac.uk