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...

Full description

Bibliographic Details
Main Authors: Carla B. Roces, Maryam T. Hussain, Signe T. Schmidt, Dennis Christensen, Yvonne Perrie
Format: Article
Language:English
Published: MDPI AG 2019-12-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/8/1/10
_version_ 1811185040394027008
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 &#215; 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.
first_indexed 2024-04-11T13:22:26Z
format Article
id doaj.art-91c5dccd262b426a9d24c7c4b79925b7
institution Directory Open Access Journal
issn 2076-393X
language English
last_indexed 2024-04-11T13:22:26Z
publishDate 2019-12-01
publisher MDPI AG
record_format Article
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 &#215; 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
work_keys_str_mv AT carlabroces investigatingprimepullvaccinationthroughacombinationofparenteralvaccinationandintranasalboosting
AT maryamthussain investigatingprimepullvaccinationthroughacombinationofparenteralvaccinationandintranasalboosting
AT signetschmidt investigatingprimepullvaccinationthroughacombinationofparenteralvaccinationandintranasalboosting
AT dennischristensen investigatingprimepullvaccinationthroughacombinationofparenteralvaccinationandintranasalboosting
AT yvonneperrie investigatingprimepullvaccinationthroughacombinationofparenteralvaccinationandintranasalboosting