Starch-based NP act as antigen delivery systems without immunomodulating effect

Abstract

The nasal route of immunization has become a real alternative to injections. It is indeed described as more efficient at inducing immune protection, since it initiates both mucosal and systemic immunity, thus protecting against both the infection itself and the transmission of pathogens by the host. However, the use of immunomodulators should be limited since they induce inflammation. Here we investigated in vitro the mechanisms underlying the enhancement of antigen immunogenicity by starch nanoparticles (NPL) delivery systems in H292 epithelial cells, as well as the NPL’s immunomodulatory effect. We observed that NPL had no intrinsic immunomodulatory effect but enhanced the immunogenicity of an E. coli lysate (Ag) merely by increasing its intracellular delivery. Moreover, we demonstrated the importance of the NPL density on their efficiency by comparing reticulated (NPL) and non-reticulated particles (NPL·NR). These results show that an efficient delivery system is sufficient to induce a mucosal immune response without the use of immunomodulators.

Nasal vaccination of six squirrel monkeys (Saimiri sciureus): Improved immunization protocol against Toxoplasma gondii with a nanoparticle-born vaccine

“…The formulation is based on maltodextrin-based nanoparticles (NPL) loaded with killed T. gondii tachyzoites. The NPL are inert and don't trigger any immune reaction by itself, but act as a delivery system to improve the antigens mucosal delivery and consequently their immunogenicity ( Bernocchi et al, 2016 ; Fasquelle et al, 2022 ). These particles were designed for the nasal route of administration, as they can cross mucus layers and enhance the mucosal residence time of antigens ( Bernocchi et al, 2016 ; Lê et al, 2019 ; Fasquelle et al, 2020 ).…”

Maltodextrin-Nanoparticles as a Delivery System for Nasal Vaccines: A Review Article

“…Studies performed on Toxoplasma gondii TE showed that 100% of the proteins were associated with the NPLs when mixed at a 1/1 weight ratio [55]. Other studies conducted with E. coli TE or with split viruses confirmed a 100% encapsulation with no release of the antigen over time [54,56].…”

“…NPLs can be loaded with up to 200% of their weight of proteins, despite the steric hindrance of the phospholipid core [ 54 ]. Measurements of the surface charge during loading indicated that proteins are fully encapsulated until 100% w / w loading is reached, and thereafter the antigens are associated with the surface of the NPL.…”

“…They were shown to deliver ovalbumin more efficiently than NPs + , probably thanks to the lipidic core promoting the endosomal escape [ 59 ]. But NPLs can also deliver complex antigens such as bacterial, parasitic and total virus extracts as a result of a strong protein encapsulation [ 54 , 56 ]. The comparative study carried out with liposomes and anionic PLGA NPs showed that NPLs increase the delivery of proteins within epithelial and immune cells [ 58 ].…”

“…Studies were conducted to establish whether these nanoparticles had an adjuvant effect on airway epithelial cells or if they acted purely as a delivery system. Interestingly, NPLs were proven to be intrinsically inert and to induce no inflammation or immunomodulation when incubated with airway epithelial and immune cells [ 54 ]. In contrast, lipid nanoparticles (LNPs), polymeric NPs or virus-like particles (VLPs) were shown to trigger innate immunity by themselves, via the activation of the inflammasome, leading to potential side effects [ 60 , 61 , 62 , 63 ].…”