Specific and Efficient Uptake of Surfactant-Free Poly(Lactic Acid) Nanovaccine Vehicles by Mucosal Dendritic Cells in Adult Zebrafish after Bath Immersion

Julien Rességuier; Emilie Delaune; Anne-Line Coolen; Jean-Pierre Levraud; Pierre Boudinot; Dominique Le Guellec; Bernard Verrier

doi:10.3389/fimmu.2017.00190

Specific and Efficient Uptake of Surfactant-Free Poly(Lactic Acid) Nanovaccine Vehicles by Mucosal Dendritic Cells in Adult Zebrafish after Bath Immersion

Front Immunol. 2017 Feb 27:8:190. doi: 10.3389/fimmu.2017.00190. eCollection 2017.

Authors

Julien Rességuier¹, Emilie Delaune¹, Anne-Line Coolen¹, Jean-Pierre Levraud², Pierre Boudinot³, Dominique Le Guellec¹, Bernard Verrier¹

Affiliations

¹ Laboratoire de Biologie Tissulaire et d'Ingénierie Thérapeutique, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique (CNRS) , Lyon , France.
² Macrophages et Développement de l'Immunité, Institut Pasteur, Centre National de la Recherche Scientifique (CNRS) , Paris , France.
³ Virologie et Immunologie Moléculaires, Institut National de la Recherche Agronomique (INRA), Université Paris-Saclay , Jouy-en-Josas , France.

Abstract

Activation of mucosal immunity is a key milestone for next-generation vaccine development. Biocompatible polymer-based nanoparticles (NPs) are promising vectors and adjuvants for mucosal vaccination. However, their in vivo uptake by mucosae and their biodistribution in antigen-presenting cells (APCs) need to be better understood to optimize mucosal nanovaccine designs. Here, we assessed if APCs are efficiently targeted in a spontaneous manner by surfactant-free poly(lactic acid) nanoparticles (PLA-NPs) after mucosal administration. Combining histology and flow imaging approaches, we describe and quantify the mucosal uptake of 200 nm PLA-NPs in adult zebrafish. Following bath administration, PLA-NPs penetrated and crossed epithelial barriers from all exposed mucosae. In mucosae, PLA-NPs accumulated in APCs, which were identified as dendritic cells (DCs), macrophages, and IgZ⁺ B cells in gills and skin. PLA-NP uptake by phagocytes was specific to these cell types, as PLA-NPs were not detected in neutrophils. Importantly, quantitative analyses in gills revealed that DCs take up PLA-NPs with specifically high efficiency. This study shows that surfactant-free PLA-NPs, which display optimal biocompatibility, can spontaneously target DCs with high efficiency in vivo following mucosal administration, and highlights PLA-NPs as powerful platforms for mucosal vaccine delivery in the medical and veterinary fields, and particularly in aquaculture.

Keywords: biodistribution; dendritic cells; imaging flow cytometry; mucosal delivery; poly(d,l-lactic acid) nanoparticles; surfactant free; vaccines carrier; zebrafish.