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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.00934

Parenteral vaccination with a tuberculosis subunit vaccine in presence of retinoic acid provides early but transient protection to M. tuberculosis infection

  • 1Department of Infectious Diseases, Istituto Superiore di Sanità (ISS), Italy
  • 2Department of Infectious Disease Immunology, State Serum Institute (SSI), Denmark
  • 3Department of Infectious Disease, Istituto Superiore di Sanità (ISS), Italy

Most microbes invading through mucosal surfaces cause disease and therefore strategies to induce mucosal immune responses are strongly needed. Vitamin A metabolites, such as retinoic acid (RA), play crucial roles in programming T and B cells to home to mucosal compartments, therefore we evaluated the capacity of RA to elicit mucosal immune responses against tuberculosis (TB) after parenteral vaccination. We found that mice immunized through subcutaneous injections with the TB subunit vaccine (CAF01+H56) in presence of RA show enhanced mucosal H56-specific IgA responses and enhanced Ag-specific CD4+ T lymphocytes homing to the lung as compared with control mice. Immunization with CAF01+H56 in presence of RA resulted in lower bacterial loads in the lungs of mice 14 days after challenge with virulent Mycobacterium tuberculosis (Mtb) as compared to mice immunized in the absence of RA or vaccinated with BCG. Higher amounts of IFNγ and IL-17 pro-inflammatory cytokine were found in lung homogenates of mice immunized with CAF01+H56 and RA 24 hours after Mtb infection. However, 6 weeks after infection the protection was comparable in vaccinated mice with or without RA even though treatment with RA during immunization is able to better contain the inflammatory response by the host. Furthermore, at later stage of the infection a higher percentage of Mtb specific CD4+PD1+ T lymphocytes were found in the lungs of mice immunized with CAF01+H56 and RA. These data show that an enhanced mucosal immune response is generated during parenteral vaccination in presence of RA. Furthermore RA treatment contained the bacterial growth at an early stage of the infection and limited the inflammatory response in the lung at later time points.

Keywords: mucosal immunity, mucosal immunization, adjuvant, Mucosal adjuvant, Retinoic acid (RA), M tuberculosis

Received: 16 Nov 2018; Accepted: 11 Apr 2019.

Edited by:

Juraj Ivanyi, King's College London, United Kingdom

Reviewed by:

Angelo Izzo, Colorado State University, United States
Rajko Reljic, St George's, University of London, United Kingdom  

Copyright: © 2019 Riccomi, Piccaro, Christensen, Palma, Andersen and Vendetti. 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(s) 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. Silvia Vendetti, Istituto Superiore di Sanità (ISS), Department of Infectious Diseases, Rome, Lazio, Italy,