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

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.

A Novel Antigen-Sampling Cell in the Teleost Gill Epithelium With the Potential for Direct Antigen Presentation in Mucosal Tissue

“…Mammalian macrophages and dendritic cells play an important role in antigen transportation. Rességuier et al ( 43 ) showed that dendritic cells take up surfactant-free poly (lactic acid) nanoparticles in the gill epithelium. In the present work, numerous gill epithelium-resident macrophage/DC-like GAS cells that contained bacterin were found following bath vaccination.…”

Lymphoid Tissue in Teleost Gills: Variations on a Theme

“…Subsequent studies in Atlantic salmon and rainbow trout (Oncorhynchus mykiss) demonstrated the presence of T lymphocytes embedded in a meshwork of reticulated epithelial cells in ILT. Only few immunoglobulin (Ig)M+ lymphocytes were detected, but the structure appears rich in cells expressing major histocompatibility complex (MHC) class II+ cells and IgT transcripts [12][13][14][15][16][17][18][19][20]. The ILT must be considered as a part of the gill-associated lymphoid tissue (GIALT), which is defined as one of the four main mucosal immune compartments found in bony fish [21].…”

Integrating fish models in tuberculosis vaccine development

“…Delivery vehicles investigated in zebrafish include single-walled carbon nanotubes (SWCNTs), nanoliposomes and biocompatible non-toxic approved materials, such as polymer-based nanoparticles [e.g. poly(lactic acid) (PLA) or poly(lactic-co-glycolic acid) (PLGA)] and other polymers (Zhang et al, 2020;Crecente-Campo et al, 2019;Ji et al, 2019;Guo et al, 2018;Lovmo et al, 2017;Resseguier et al, 2017;Ruyra et al, 2014). Studies in both adult and larval zebrafish have demonstrated that nanoparticles can cross the tissue epithelium and be taken up by antigenpresenting cells (Zhang et al, 2020;Resseguier et al, 2017) and other leukocytes (Lovmo et al, 2017).…”

“…poly(lactic acid) (PLA) or poly(lactic-co-glycolic acid) (PLGA)] and other polymers ( Zhang et al, 2020 ; Crecente-Campo et al, 2019 ; Ji et al, 2019 ; Guo et al, 2018 ; Lovmo et al, 2017 ; Resseguier et al, 2017 ; Ruyra et al, 2014 ). Studies in both adult and larval zebrafish have demonstrated that nanoparticles can cross the tissue epithelium and be taken up by antigen-presenting cells ( Zhang et al, 2020 ; Resseguier et al, 2017 ) and other leukocytes ( Lovmo et al, 2017 ). Crecente-Campo et al (2019) , in turn, have investigated the effect of particle size on phagocytosis and antigen presentation by macrophages.…”