Investigating Prime-Pull Vaccination through a Combination of Parenteral Vaccination and Intranasal Boosting
Formulation of inhalable delivery systems containing tuberculosis (TB) antigens to target the site of infection (lungs) have been considered for the development of subunit vaccines. Inert delivery systems such as poly (lactic-co-glycolic acid) (PLGA) are an interesting approach due to its approval f...
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MDPI AG
2019-12-01
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Series: | Vaccines |
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Online Access: | https://www.mdpi.com/2076-393X/8/1/10 |
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author | Carla B. Roces Maryam T. Hussain Signe T. Schmidt Dennis Christensen Yvonne Perrie |
author_facet | Carla B. Roces Maryam T. Hussain Signe T. Schmidt Dennis Christensen Yvonne Perrie |
author_sort | Carla B. Roces |
collection | DOAJ |
description | Formulation of inhalable delivery systems containing tuberculosis (TB) antigens to target the site of infection (lungs) have been considered for the development of subunit vaccines. Inert delivery systems such as poly (lactic-co-glycolic acid) (PLGA) are an interesting approach due to its approval for human use. However, PLGA suffers hydrolytic degradation when stored in a liquid environment for prolonged time. Therefore, in this study, nano- and microparticles composed of different PLGA copolymers (50:50, 75:25 and 85:15), sucrose (10% <i>w</i>/<i>v</i>) and L-leucine (1% <i>w</i>/<i>v</i>) encapsulating H56 TB vaccine candidate were produced as dried powders. In vitro studies in three macrophage cell lines (MH-S, RAW264.7 and THP-1) showed the ability of these cells to take up the formulated PLGA:H56 particles and process the antigen. An in vivo prime-pull immunisation approach consisting of priming with CAF01:H56 (2 × subcutaneous (s.c.) injection) followed by a mucosal boost with PLGA:H56 (intranasal (i.n.) administration) demonstrated the retention of the immunogenicity of the antigen encapsulated within the lyophilised PLGA delivery system, although no enhancing effect could be observed compared to the administration of antigen alone as a boost. The work here could provide the foundations for the scale independent manufacture of polymer delivery systems encapsulating antigens for inhalation/aerolisation to the lungs. |
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institution | Directory Open Access Journal |
issn | 2076-393X |
language | English |
last_indexed | 2024-04-11T13:22:26Z |
publishDate | 2019-12-01 |
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series | Vaccines |
spelling | doaj.art-91c5dccd262b426a9d24c7c4b79925b72022-12-22T04:22:09ZengMDPI AGVaccines2076-393X2019-12-01811010.3390/vaccines8010010vaccines8010010Investigating Prime-Pull Vaccination through a Combination of Parenteral Vaccination and Intranasal BoostingCarla B. Roces0Maryam T. Hussain1Signe T. Schmidt2Dennis Christensen3Yvonne Perrie4Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UKStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UKCenter for Vaccine Research, Statens Serum Institut, 2300 Copenhagen, DenmarkCenter for Vaccine Research, Statens Serum Institut, 2300 Copenhagen, DenmarkStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UKFormulation of inhalable delivery systems containing tuberculosis (TB) antigens to target the site of infection (lungs) have been considered for the development of subunit vaccines. Inert delivery systems such as poly (lactic-co-glycolic acid) (PLGA) are an interesting approach due to its approval for human use. However, PLGA suffers hydrolytic degradation when stored in a liquid environment for prolonged time. Therefore, in this study, nano- and microparticles composed of different PLGA copolymers (50:50, 75:25 and 85:15), sucrose (10% <i>w</i>/<i>v</i>) and L-leucine (1% <i>w</i>/<i>v</i>) encapsulating H56 TB vaccine candidate were produced as dried powders. In vitro studies in three macrophage cell lines (MH-S, RAW264.7 and THP-1) showed the ability of these cells to take up the formulated PLGA:H56 particles and process the antigen. An in vivo prime-pull immunisation approach consisting of priming with CAF01:H56 (2 × subcutaneous (s.c.) injection) followed by a mucosal boost with PLGA:H56 (intranasal (i.n.) administration) demonstrated the retention of the immunogenicity of the antigen encapsulated within the lyophilised PLGA delivery system, although no enhancing effect could be observed compared to the administration of antigen alone as a boost. The work here could provide the foundations for the scale independent manufacture of polymer delivery systems encapsulating antigens for inhalation/aerolisation to the lungs.https://www.mdpi.com/2076-393X/8/1/10plgaadjuvantsprime-pulltuberculosispowderlungs |
spellingShingle | Carla B. Roces Maryam T. Hussain Signe T. Schmidt Dennis Christensen Yvonne Perrie Investigating Prime-Pull Vaccination through a Combination of Parenteral Vaccination and Intranasal Boosting Vaccines plga adjuvants prime-pull tuberculosis powder lungs |
title | Investigating Prime-Pull Vaccination through a Combination of Parenteral Vaccination and Intranasal Boosting |
title_full | Investigating Prime-Pull Vaccination through a Combination of Parenteral Vaccination and Intranasal Boosting |
title_fullStr | Investigating Prime-Pull Vaccination through a Combination of Parenteral Vaccination and Intranasal Boosting |
title_full_unstemmed | Investigating Prime-Pull Vaccination through a Combination of Parenteral Vaccination and Intranasal Boosting |
title_short | Investigating Prime-Pull Vaccination through a Combination of Parenteral Vaccination and Intranasal Boosting |
title_sort | investigating prime pull vaccination through a combination of parenteral vaccination and intranasal boosting |
topic | plga adjuvants prime-pull tuberculosis powder lungs |
url | https://www.mdpi.com/2076-393X/8/1/10 |
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