Investigating the impact of delivery system design on the efficacy of self-amplifying RNA vaccines

Giulia Anderluzzi; Gustavo Lou; Simona Gallorini; Michela Brazzoli; Russell Johnson; Derek T. O'Hagan; Barbara C. Baudner; Yvonne Perrie

doi:10.3390/vaccines8020212

Investigating the impact of delivery system design on the efficacy of self-amplifying RNA vaccines

Giulia Anderluzzi, Gustavo Lou, Simona Gallorini, Michela Brazzoli, Russell Johnson, Derek T. O'Hagan, Barbara C. Baudner, Yvonne Perrie

Strathclyde Institute Of Pharmacy And Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

23 Citations (Scopus)

17 Downloads (Pure)

Abstract

Messenger RNA (mRNA)-based vaccines combine the positive attributes of both live-attenuated and subunit vaccines. In order for these to be applied for clinical use, they require to be formulated with delivery systems. However, there are limited in vivo studies which compare different delivery platforms. Therefore, we have compared four different cationic platforms: (1) liposomes, (2) solid lipid nanoparticles (SLNs), (3) polymeric nanoparticles (NPs) and (4) emulsions, to deliver a self-amplifying mRNA (SAM) vaccine. All formulations contained either the non-ionizable cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or dimethyldioctadecylammonium bromide (DDA) and they were characterized in terms of physico-chemical attributes, in vitro transfection efficiency and in vivo vaccine potency. Our results showed that SAM encapsulating DOTAP polymeric nanoparticles, DOTAP liposomes and DDA liposomes induced the highest antigen expression in vitro and, from these, DOTAP polymeric nanoparticles were the most potent in triggering humoral and cellular immunity among candidates in vivo.

Original language	English
Article number	212
Number of pages	22
Journal	Vaccines
Volume	8
Issue number	2
DOIs	https://doi.org/10.3390/vaccines8020212
Publication status	Published - 8 May 2020

Keywords

vaccines
liposomes
LNPs
self-amplifying RNA

Access to Document

10.3390/vaccines8020212Licence: CC BY 4.0

Anderluzzi-etal-Vaccines-2020-Investigating-the-impact-of-delivery-system-desig--on-the-efficacy-of-self-amplifyingFinal published version, 2.19 MBLicence: CC BY 4.0

Yvonne Perrie
- yvonne.perriestrath.acuk
- Strathclyde Institute Of Pharmacy And Biomedical Sciences - Professor
Person: Academic

1 Finished

Leveraging Pharmaceutical Sciences and Structural Biology Training to develop 21st Century Vaccines PHA-ST-TRAIN-VAC (H2020 MCSA EID)
Perrie, Y.
European Commission - Horizon 2020
1/06/16 → 31/05/20
Project: Research

Data for: "Investigating the impact of delivery system design on the efficacy of self-amplifying RNA vaccines"
Perrie, Y. (Creator), Anderluzzi, G. (Creator) & Lou Ramirez, G. (Creator), University of Strathclyde, 1 May 2020
DOI: 10.15129/2d34fc56-373e-44cc-9937-150afb28b752
Dataset

23 Citations
2 Article

Using microfluidics for scalable manufacturing of nanomedicines from bench to GMP: a case study using protein-loaded liposomes
Webb, C., Forbes, N., Roces, C. B., Anderluzzi, G., Lou, G., Abraham, S., Ingalls, L., Marshall, K., Leaver, T. J., Watts, J. A., Aylott, J. W. & Perrie, Y., 30 May 2020, In: International Journal of Pharmaceutics. 582, 12 p., 119266.
Research output: Contribution to journal › Article › peer-review

Open Access
File
56 Citations (Scopus)

257 Downloads (Pure)
Microfluidic manufacture of solid lipid nanoparticles: a case study on tristearin-based systems
Anderluzzi, G. & Perrie, Y., 31 Dec 2019, (E-pub ahead of print) In: Drug Delivery Letters. 25 p.
Research output: Contribution to journal › Article › peer-review

Open Access
File
2 Citations (Scopus)

216 Downloads (Pure)

Cite this

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title = "Investigating the impact of delivery system design on the efficacy of self-amplifying RNA vaccines",

abstract = "Messenger RNA (mRNA)-based vaccines combine the positive attributes of both live-attenuated and subunit vaccines. In order for these to be applied for clinical use, they require to be formulated with delivery systems. However, there are limited in vivo studies which compare different delivery platforms. Therefore, we have compared four different cationic platforms: (1) liposomes, (2) solid lipid nanoparticles (SLNs), (3) polymeric nanoparticles (NPs) and (4) emulsions, to deliver a self-amplifying mRNA (SAM) vaccine. All formulations contained either the non-ionizable cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or dimethyldioctadecylammonium bromide (DDA) and they were characterized in terms of physico-chemical attributes, in vitro transfection efficiency and in vivo vaccine potency. Our results showed that SAM encapsulating DOTAP polymeric nanoparticles, DOTAP liposomes and DDA liposomes induced the highest antigen expression in vitro and, from these, DOTAP polymeric nanoparticles were the most potent in triggering humoral and cellular immunity among candidates in vivo. ",

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author = "Giulia Anderluzzi and Gustavo Lou and Simona Gallorini and Michela Brazzoli and Russell Johnson and O'Hagan, {Derek T.} and Baudner, {Barbara C.} and Yvonne Perrie",

year = "2020",

month = may,

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doi = "10.3390/vaccines8020212",

language = "English",

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AU - Anderluzzi, Giulia

AU - Lou, Gustavo

AU - Gallorini, Simona

AU - Brazzoli, Michela

AU - Johnson, Russell

AU - O'Hagan, Derek T.

AU - Baudner, Barbara C.

AU - Perrie, Yvonne

PY - 2020/5/8

Y1 - 2020/5/8

N2 - Messenger RNA (mRNA)-based vaccines combine the positive attributes of both live-attenuated and subunit vaccines. In order for these to be applied for clinical use, they require to be formulated with delivery systems. However, there are limited in vivo studies which compare different delivery platforms. Therefore, we have compared four different cationic platforms: (1) liposomes, (2) solid lipid nanoparticles (SLNs), (3) polymeric nanoparticles (NPs) and (4) emulsions, to deliver a self-amplifying mRNA (SAM) vaccine. All formulations contained either the non-ionizable cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or dimethyldioctadecylammonium bromide (DDA) and they were characterized in terms of physico-chemical attributes, in vitro transfection efficiency and in vivo vaccine potency. Our results showed that SAM encapsulating DOTAP polymeric nanoparticles, DOTAP liposomes and DDA liposomes induced the highest antigen expression in vitro and, from these, DOTAP polymeric nanoparticles were the most potent in triggering humoral and cellular immunity among candidates in vivo.

AB - Messenger RNA (mRNA)-based vaccines combine the positive attributes of both live-attenuated and subunit vaccines. In order for these to be applied for clinical use, they require to be formulated with delivery systems. However, there are limited in vivo studies which compare different delivery platforms. Therefore, we have compared four different cationic platforms: (1) liposomes, (2) solid lipid nanoparticles (SLNs), (3) polymeric nanoparticles (NPs) and (4) emulsions, to deliver a self-amplifying mRNA (SAM) vaccine. All formulations contained either the non-ionizable cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or dimethyldioctadecylammonium bromide (DDA) and they were characterized in terms of physico-chemical attributes, in vitro transfection efficiency and in vivo vaccine potency. Our results showed that SAM encapsulating DOTAP polymeric nanoparticles, DOTAP liposomes and DDA liposomes induced the highest antigen expression in vitro and, from these, DOTAP polymeric nanoparticles were the most potent in triggering humoral and cellular immunity among candidates in vivo.

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KW - LNPs

KW - self-amplifying RNA

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VL - 8

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JF - Vaccines

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ER -

Investigating the impact of delivery system design on the efficacy of self-amplifying RNA vaccines

Abstract

Keywords

Access to Document

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Profiles

Yvonne Perrie

Projects

Leveraging Pharmaceutical Sciences and Structural Biology Training to develop 21st Century Vaccines PHA-ST-TRAIN-VAC (H2020 MCSA EID)

Datasets

Data for: "Investigating the impact of delivery system design on the efficacy of self-amplifying RNA vaccines"

Research output

Using microfluidics for scalable manufacturing of nanomedicines from bench to GMP: a case study using protein-loaded liposomes

Microfluidic manufacture of solid lipid nanoparticles: a case study on tristearin-based systems

Cite this