A Polylactide-Based Micellar Adjuvant Improves the Intensity and Quality of Immune Response.
Myriam LamrayahCapucine PhelipCéline CoiffierCéline LacroixThibaut WilleminThomas TrimailleBernard VerrierPublished in: Pharmaceutics (2022)
Micelles from amphiphilic polylactide-block-poly( N -acryloxysuccinimide- co - N -vinylpyrrolidone) (PLA-b-P(NAS- co -NVP)) block copolymers of 105 nm in size were characterized and evaluated in a vaccine context. The micelles were non-toxic in vitro (both in dendritic cells and HeLa cells). In vitro fluorescence experiments combined with in vivo fluorescence tomography imaging, through micelle loading with the DiR near infrared probe, suggested an efficient uptake of the micelles by the immune cells. The antigenic protein p24 of the HIV-1 was successfully coupled on the micelles using the reactive N -succinimidyl ester groups on the micelle corona, as shown by SDS-PAGE analyses. The antigenicity of the coupled antigen was preserved and even improved, as assessed by the immuno-enzymatic (ELISA) test. Then, the performances of the micelles in immunization were investigated and compared to different p24-coated PLA nanoparticles, as well as Alum and MF59 gold standards, following a standardized HIV-1 immunization protocol in mice. The humoral response intensity (IgG titers) was substantially similar between the PLA micelles and all other adjuvants over an extended time range (one year). More interestingly, this immune response induced by PLA micelles was qualitatively higher than the gold standards and PLA nanoparticles analogs, expressed through an increasing avidity index over time (>60% at day 365). Taken together, these results demonstrate the potential of such small-sized micellar systems for vaccine delivery.
Keyphrases
- drug delivery
- immune response
- drug release
- cancer therapy
- dendritic cells
- hyaluronic acid
- antiretroviral therapy
- hiv infected
- hiv positive
- human immunodeficiency virus
- hiv aids
- early stage
- hiv testing
- single molecule
- high resolution
- cell cycle arrest
- high intensity
- type diabetes
- molecular docking
- skeletal muscle
- protein protein
- regulatory t cells
- mass spectrometry
- south africa
- fluorescence imaging
- insulin resistance