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Poly-(lactic-co-glycolic-acid)-based particulate vaccines: Particle uptake by dendritic cells is a key parameter for immune activation


Silva, A L; Rosalia, R A; Varypataki, E; Sibuea, S; Ossendorp, F; Jiskoot, W (2015). Poly-(lactic-co-glycolic-acid)-based particulate vaccines: Particle uptake by dendritic cells is a key parameter for immune activation. Vaccine, 33(7):847-854.

Abstract

Poly(lactic-co-glycolic acid) (PLGA) particles have been extensively studied as biodegradable delivery system to improve the potency and safety of protein-based vaccines. In this study we analyzed how the size of PLGA particles, and hence their ability to be engulfed by dendritic cells (DC), affects the type and magnitude of the immune response in comparison to sustained release from a local depot. PLGA microparticles (MP, volume mean diameter ≈ 112 μm) and nanoparticles (NP, Z-average diameter ≈ 350 nm) co-encapsulating ovalbumin (OVA) and poly(I:C), with comparable antigen (Ag) release characteristics, were prepared and characterized. The immunogenicity of these two distinct particulate vaccines was evaluated in vitro and in vivo. NP were efficiently taken up by DC and greatly facilitated MHC I Ag presentation in vitro, whereas DC cultured in the presence of MP failed to internalize significant amounts of Ag and hardly showed MHC I Ag presentation. Vaccination of mice with NP resulted in significantly better priming of Ag-specific CD8+ T cells compared to MP and OVA emulsified with incomplete Freund's adjuvant (IFA). Moreover, NP induced a balanced TH1/TH2-type antibody response, compared to vaccinations with IFA which stimulated a predominant TH2-type response, whereas MP failed to increase antibody titers. In conclusion, we postulate that particle internalization is of crucial importance and therefore particulate vaccines should be formulated in the nano- but not micro-size range to achieve efficient uptake, significant MHC class I cross-presentation and effective T and B cell responses.

Abstract

Poly(lactic-co-glycolic acid) (PLGA) particles have been extensively studied as biodegradable delivery system to improve the potency and safety of protein-based vaccines. In this study we analyzed how the size of PLGA particles, and hence their ability to be engulfed by dendritic cells (DC), affects the type and magnitude of the immune response in comparison to sustained release from a local depot. PLGA microparticles (MP, volume mean diameter ≈ 112 μm) and nanoparticles (NP, Z-average diameter ≈ 350 nm) co-encapsulating ovalbumin (OVA) and poly(I:C), with comparable antigen (Ag) release characteristics, were prepared and characterized. The immunogenicity of these two distinct particulate vaccines was evaluated in vitro and in vivo. NP were efficiently taken up by DC and greatly facilitated MHC I Ag presentation in vitro, whereas DC cultured in the presence of MP failed to internalize significant amounts of Ag and hardly showed MHC I Ag presentation. Vaccination of mice with NP resulted in significantly better priming of Ag-specific CD8+ T cells compared to MP and OVA emulsified with incomplete Freund's adjuvant (IFA). Moreover, NP induced a balanced TH1/TH2-type antibody response, compared to vaccinations with IFA which stimulated a predominant TH2-type response, whereas MP failed to increase antibody titers. In conclusion, we postulate that particle internalization is of crucial importance and therefore particulate vaccines should be formulated in the nano- but not micro-size range to achieve efficient uptake, significant MHC class I cross-presentation and effective T and B cell responses.

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19 citations in Web of Science®
20 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Immunology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2015
Deposited On:28 Jan 2016 13:59
Last Modified:05 Apr 2016 20:03
Publisher:Elsevier
ISSN:0264-410X
Publisher DOI:https://doi.org/10.1016/j.vaccine.2014.12.059

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