Role of sustained antigen release from nanoparticle vaccines in shaping the T cell memory phenotype

Abstract

Particulate vaccines are emerging promising technologies for the creation of tunable prophylactics against a wide variety of conditions. Vesicular and solid biodegradable polymer platforms, exemplified by liposomes and polyesters, respectively, are two of the most ubiquitous platforms in vaccine delivery studies. Here we directly compared the efficacy of each in a long-term immunization study and in protection against a model bacterial antigen. Immunization with poly(lactide-co-glycolide) (PLGA) nanoparticles elicited prolonged antibody titers compared to liposomes and alum. The magnitude of the cellular immune response was also highest in mice vaccinated with PLGA, which also showed a higher frequency of effector-like memory T cell phenotype, leading to an effective clearance of intracellular bacteria. The difference in performance of these two common particulate platforms is shown not to be due to material differences but appears to be connected to the kinetics of antigen delivery. Thus, this study highlights the importance of sustained antigen release mediated by particulate platforms and its role in the long-term appearance of effector memory cellular response.

Hollow microneedle-mediated intradermal delivery of model vaccine antigen-loaded PLGA nanoparticles elicits protective T cell-mediated immunity to an intracellular bacterium

“…Difference in antigen release can have a role in shaping the memory phenotype [47], however we found similar release profiles. Further analysis of CD8 + T cell phenotype showed that there was no difference within percentage of Tcm and Tem/Teff cells between the different PLGA NP immunized groups, but an enhanced ratio of CD8 + T cells with CD44 int phenotype was detected in mice immune to rLM-OVA challenge.…”

Targeting human dendritic cells via DEC-205 using PLGA nanoparticles leads to enhanced cross-presentation of a melanoma-associated antigen

“…Currently, there are no human peptide-based cancer vaccines on the market, mostly because of the difficulties associated with their poor immunogenicity, stability, and delivery. Our group 15,17,[35][36][37][38] and others [39][40][41][42] have described strategies to enhance peptide/protein immunogenicity and stability by directing Ag to DCs using particulate delivery systems. The particulate nature of these delivery vehicles permits their rapid internalization by DCs and their composition can provide adjuvant properties required for immunogenicity.…”

Nanoparticulate STING agonists are potent lymph node–targeted vaccine adjuvants

“…Nanoparticle vehicles, such as polymer particles or liposomes, can promote adjuvant transport through lymphatics to draining lymph nodes (dLNs), while blocking dissemination into the systemic circulation (25,26). Concentration of molecular adjuvants in lymph nodes (LNs) using nanoparticle carriers can enable profound dose sparing of molecular adjuvants, and this approach has been demonstrated for a number of TLR agonists, including MPLA, CpG DNA, poly(I:C), and small-molecule TLR7/8 compounds (27)(28)(29)(30)(31)(32)(33). Importantly, a number of TLR agonist-carrying particle formulations have been demonstrated to effectively adjuvant the immune response when simply admixed with particulate or soluble antigen, i.e., without requiring coincorporation of antigen and adjuvant together in particles (32,(34)(35)(36).…”