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Immunization With Mycobacterium tuberculosis Antigens Encapsulated in Phosphatidylserine Liposomes Improves Protection Afforded by BCG

Liposomes have been long considered as a vaccine delivery system but this technology remains to be fully utilized. Here, we describe a novel liposome-based subunit vaccine formulation for tuberculosis (TB) based on phosphatidylserine encapsulating two prominent TB antigens, Ag85B, and ESAT-6. We sho...

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Autores principales: Diogo, Gil R., Hart, Peter, Copland, Alastair, Kim, Mi-Young, Tran, Andy C., Poerio, Noemi, Singh, Mahavir, Paul, Matthew J., Fraziano, Maurizio, Reljic, Rajko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598733/
https://www.ncbi.nlm.nih.gov/pubmed/31293568
http://dx.doi.org/10.3389/fimmu.2019.01349
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author Diogo, Gil R.
Hart, Peter
Copland, Alastair
Kim, Mi-Young
Tran, Andy C.
Poerio, Noemi
Singh, Mahavir
Paul, Matthew J.
Fraziano, Maurizio
Reljic, Rajko
author_facet Diogo, Gil R.
Hart, Peter
Copland, Alastair
Kim, Mi-Young
Tran, Andy C.
Poerio, Noemi
Singh, Mahavir
Paul, Matthew J.
Fraziano, Maurizio
Reljic, Rajko
author_sort Diogo, Gil R.
collection PubMed
description Liposomes have been long considered as a vaccine delivery system but this technology remains to be fully utilized. Here, we describe a novel liposome-based subunit vaccine formulation for tuberculosis (TB) based on phosphatidylserine encapsulating two prominent TB antigens, Ag85B, and ESAT-6. We show that the resulting liposomes (Lipo-AE) are stable upon storage and can be readily taken up by antigen presenting cells and that their antigenic cargo is delivered and processed within endosomal cell compartments. The Lipo-AE vaccine formulation combined with the PolyIC adjuvant induced a mixed Th1/Th17-Th2 immune response to Ag85B but only a weak response to ESAT-6. An immunization regimen based on systemic delivery followed by mucosal boost with Lipo-AE resulted in the accumulation of resident memory T cells in the lungs. Most importantly though, when Lipo-AE vaccine candidate was administered to BCG-immunized mice subsequently challenged with low dose aerosol Mycobacterium tuberculosis, we observed a significant reduction of the bacterial load in the lungs and spleen compared to BCG alone. We therefore conclude that the immunization with mycobacterial antigens delivered by phosphatidylserine based liposomes in combination with Poly:IC adjuvant may represent a novel BCG boosting vaccination strategy.
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spelling pubmed-65987332019-07-10 Immunization With Mycobacterium tuberculosis Antigens Encapsulated in Phosphatidylserine Liposomes Improves Protection Afforded by BCG Diogo, Gil R. Hart, Peter Copland, Alastair Kim, Mi-Young Tran, Andy C. Poerio, Noemi Singh, Mahavir Paul, Matthew J. Fraziano, Maurizio Reljic, Rajko Front Immunol Immunology Liposomes have been long considered as a vaccine delivery system but this technology remains to be fully utilized. Here, we describe a novel liposome-based subunit vaccine formulation for tuberculosis (TB) based on phosphatidylserine encapsulating two prominent TB antigens, Ag85B, and ESAT-6. We show that the resulting liposomes (Lipo-AE) are stable upon storage and can be readily taken up by antigen presenting cells and that their antigenic cargo is delivered and processed within endosomal cell compartments. The Lipo-AE vaccine formulation combined with the PolyIC adjuvant induced a mixed Th1/Th17-Th2 immune response to Ag85B but only a weak response to ESAT-6. An immunization regimen based on systemic delivery followed by mucosal boost with Lipo-AE resulted in the accumulation of resident memory T cells in the lungs. Most importantly though, when Lipo-AE vaccine candidate was administered to BCG-immunized mice subsequently challenged with low dose aerosol Mycobacterium tuberculosis, we observed a significant reduction of the bacterial load in the lungs and spleen compared to BCG alone. We therefore conclude that the immunization with mycobacterial antigens delivered by phosphatidylserine based liposomes in combination with Poly:IC adjuvant may represent a novel BCG boosting vaccination strategy. Frontiers Media S.A. 2019-06-12 /pmc/articles/PMC6598733/ /pubmed/31293568 http://dx.doi.org/10.3389/fimmu.2019.01349 Text en Copyright © 2019 Diogo, Hart, Copland, Kim, Tran, Poerio, Singh, Paul, Fraziano and Reljic. http://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Immunology
Diogo, Gil R.
Hart, Peter
Copland, Alastair
Kim, Mi-Young
Tran, Andy C.
Poerio, Noemi
Singh, Mahavir
Paul, Matthew J.
Fraziano, Maurizio
Reljic, Rajko
Immunization With Mycobacterium tuberculosis Antigens Encapsulated in Phosphatidylserine Liposomes Improves Protection Afforded by BCG
title Immunization With Mycobacterium tuberculosis Antigens Encapsulated in Phosphatidylserine Liposomes Improves Protection Afforded by BCG
title_full Immunization With Mycobacterium tuberculosis Antigens Encapsulated in Phosphatidylserine Liposomes Improves Protection Afforded by BCG
title_fullStr Immunization With Mycobacterium tuberculosis Antigens Encapsulated in Phosphatidylserine Liposomes Improves Protection Afforded by BCG
title_full_unstemmed Immunization With Mycobacterium tuberculosis Antigens Encapsulated in Phosphatidylserine Liposomes Improves Protection Afforded by BCG
title_short Immunization With Mycobacterium tuberculosis Antigens Encapsulated in Phosphatidylserine Liposomes Improves Protection Afforded by BCG
title_sort immunization with mycobacterium tuberculosis antigens encapsulated in phosphatidylserine liposomes improves protection afforded by bcg
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598733/
https://www.ncbi.nlm.nih.gov/pubmed/31293568
http://dx.doi.org/10.3389/fimmu.2019.01349
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