AUTHOR=Kuczkowska Katarzyna , Copland Alastair , Øverland Lise , Mathiesen Geir , Tran Andy C. , Paul Mathew J. , Eijsink Vincent G. H. , Reljic Rajko 

TITLE=Inactivated Lactobacillus plantarum Carrying a Surface-Displayed Ag85B-ESAT-6 Fusion Antigen as a Booster Vaccine Against Mycobacterium tuberculosis Infection

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01588

DOI=10.3389/fimmu.2019.01588

ISSN=1664-3224

ABSTRACT=<p>Vaccination is considered the most effective strategy for controlling tuberculosis (TB). The existing vaccine, the Bacille Calmette-Guérin (BCG), although partially protective, has a number of limitations. Therefore, there is a need for developing new TB vaccines and several strategies are currently exploited including the use of viral and bacterial delivery vectors. We have previously shown that <italic>Lactobacillus plantarum</italic> (<italic>Lp</italic>) producing Ag85B and ESAT-6 antigens fused to a dendritic cell-targeting peptide (referred to as <italic>Lp</italic>_DC) induced specific immune responses in mice. Here, we analyzed the ability of two <italic>Lp</italic>-based vaccines, <italic>Lp</italic>_DC and <italic>Lp</italic>_HBD (in which the DC-binding peptide was replaced by an HBD-domain directing the antigen to non-phagocytic cells) to activate antigen-presenting cells, induce specific immunity and protect mice from <italic>Mycobacterium tuberculosis</italic> infection. We tested two strategies: (i) <italic>Lp</italic> as BCG boosting vaccine (a heterologous regimen comprising parenteral BCG immunization followed by intranasal <italic>Lp</italic> boost), and (ii) <italic>Lp</italic> as primary vaccine (a homologous regimen including subcutaneous priming followed by intranasal boost). The results showed that both <italic>Lp</italic> constructs applied as a BCG boost induced specific cellular immunity, manifested in T cell proliferation, antigen-specific IFN-γ responses and multifunctional T cells phenotypes. More importantly, intranasal boost with <italic>Lp</italic>_DC or <italic>Lp</italic>_HBD enhanced protection offered by BCG, as shown by reduced <italic>M. tuberculosis</italic> counts in lungs. These findings suggest that <italic>Lp</italic> constructs could be developed as a potential mucosal vaccine platform against mycobacterial infections.</p>