Kuczkowska, K; Copland, A; Overland, L; Mathiesen, G; Tran, AC; Paul, MJ; Eijsink, VGH; Reljic, R
(2019)
Inactivated Lactobacillus plantarum Carrying a Surface-Displayed Ag85B-ESAT-6 Fusion Antigen as a Booster Vaccine Against Mycobacterium tuberculosis Infection.
FRONTIERS IN IMMUNOLOGY, 10.
p. 1588.
ISSN 1664-3224
https://doi.org/10.3389/fimmu.2019.01588
SGUL Authors: Reljic, Rajko
Abstract
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 Lactobacillus plantarum (Lp) producing Ag85B and ESAT-6 antigens fused to a dendritic cell-targeting peptide (referred to as Lp_DC) induced specific immune responses in mice. Here, we analyzed the ability of two Lp-based vaccines, Lp_DC and Lp_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 Mycobacterium tuberculosis infection. We tested two strategies: (i) Lp as BCG boosting vaccine (a heterologous regimen comprising parenteral BCG immunization followed by intranasal Lp boost), and (ii) Lp as primary vaccine (a homologous regimen including subcutaneous priming followed by intranasal boost). The results showed that both Lp 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 Lp_DC or Lp_HBD enhanced protection offered by BCG, as shown by reduced M. tuberculosis counts in lungs. These findings suggest that Lp constructs could be developed as a potential mucosal vaccine platform against mycobacterial infections.
Item Type: |
Article
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Additional Information: |
Copyright © 2019 Kuczkowska, Copland, Øverland, Mathiesen, Tran, Paul, Eijsink 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(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. |
Keywords: |
tuberculosis, vaccine, lactic acid bacteria, Lactobacillus plantarum, adjuvant, delivery vector |
SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
Journal or Publication Title: |
FRONTIERS IN IMMUNOLOGY |
ISSN: |
1664-3224 |
Dates: |
Date | Event |
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9 July 2019 | Published | 25 June 2019 | Accepted |
|
Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
Project ID | Funder | Funder ID |
---|
234502 | Research Council of Norway | UNSPECIFIED | 643558 | Horizon 2020 | UNSPECIFIED |
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Web of Science ID: |
WOS:000474765500001 |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/111030 |
Publisher's version: |
https://doi.org/10.3389/fimmu.2019.01588 |
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