Poly(allylamine)-tripolyphosphate polymeric nanoparticle as an NLRP3-dependent systemic adjuvant for the vaccine development

Abstract

Nanotechnology plays a crucial role in vaccine development. It allows the design of functional nanoparticles (NPs) that can act both as antigen carriers and as adjuvants to enhance the immune response. The present study aims to evaluate complex coacervate-like NPs composed of poly(allylamine hydrochloride) (PAH) and tripolyphosphate (TPP) as a safe vehicle and adjuvant for systemic vaccines. We investigated the activation of different antigen-presenting cells (APCs) with NPs and their adjuvanticity in Balbc/c and different KO mice that were intraperitoneally immunized with NP-OVA. We found that NPs increased the expression of CD86 and MHCII and promoted the production and secretion of interleukin-1{beta} (IL-1{beta}) and IL-18 through the inflammasome NLRP3 when macrophages and dendritic cells were co-incubated with LPS and NPs. We evidenced an unconventional IL-1{beta} release through the autophagosome pathway. The inhibition of autophagy with 3-methyladenine reduced the LPS/NPs-induced IL-1{beta} secretion. Additionally, our findings showed that the systemic administration of mice with NP-OVA triggered a significant induction of serum OVA-specific IgG and IgG2a, an increased secretion of IFN-{gamma} by spleen cells, and high frequencies of LT CD4+IFN-{gamma}+ and LT CD8+IFN-{gamma}+. Our findings show that NPs promoted the inflammasome activation of innate cells with Th1-dependent adjuvant properties, making them valuable for formulating novel preventive or therapeutic vaccines for infectious and non-infectious diseases. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=193 HEIGHT=200 SRC="FIGDIR/small/601578v2_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@60d382org.highwire.dtl.DTLVardef@de17b2org.highwire.dtl.DTLVardef@e5aebeorg.highwire.dtl.DTLVardef@13347b0_HPS_FORMAT_FIGEXP M_FIG C_FIG