In Situ Polymerization-Mediated Antigen Presentation

Abstract

Activating antigen-presenting cells is essential to generate adaptive immunity, while the efficacy of conventional activation strategies remains unsatisfactory due to suboptimal antigen-specific priming. Here, in situ polymerization-mediated antigen presentation (IPAP) is described, in which antigen-loaded nanovaccines are spontaneously formed and efficiently anchored onto the surface of dendritic cells in vivo through co-deposition with dopamine. The resulting chemically bound nanovaccines can promote antigen presentation by elevating macropinocytosis-based cell uptake and reducing lysosome-related antigen degradation. IPAP is able to prolong the duration of antigen reservation in the injection site and enhance subsequent accumulation in the draining lymph nodes, thereby eliciting robust antigen-specific cellular and humoral immune responses. IPAP is also applicable for different antigens and capable of circumventing the disadvantages of complicated preparation and purification. By implementation with ovalbumin, IPAP induces a significant protective immunity against ovalbumin-overexpressing tumor cell challenge in a prophylactic murine model. The use of the SARS-CoV-2 Spike protein S1 subunit also remarkably increases the production of S1-specific immunoglobulin G in mice. IPAP offers a unique strategy for stimulating antigen-presenting cells to boost antigen-specific adaptive responses and proposes a facile yet versatile method for immunization against various diseases.

Bacterial Biohybrids for Invasion of Tumor Cells Promote Antigen Cross‐Presentation Through Gap Junction

“…Besides, we further evaluated the extent of specific T cell activation through flow cytometry by detecting IFN‐γ, a marker of T cell activation. [ 19,34 ] The proportion of IFN‐γ + CD8 + T cells in the spleen of VNP@COS‐M treatment group was the highest (Figures 6g; and S20, Supporting Information). In summary, VNP@COS‐M can activate specific immune responses in vivo and can effectively induce anti‐tumor immunity.…”

“…Presently, studies related to specific immune activation predominantly concentrate on the direct targeting of APCs for the presentation of tumor antigens and the reversal of tumor immunosuppressive microenvironment to promote antigen crosspresentation. [17][18][19] Nevertheless, the diminished response rate to tumor antigens and immune evasion associated with these approaches limit the efficacy of specific immune activation. [20,21] In addition, tumor cells can evade specific T cell surveillance by down-regulating surface MHC-I molecules.…”

Click‐Chemistry‐Mediated Cell Membrane Glycopolymer Engineering to Potentiate Dendritic Cell Vaccines

“…The antigen presented by matured DCs is critical for the activation of CD8 + T cells and subsequent anti-tumor immune responses. [15] In this study, OVA/F-PEI nanoparticles (OVA/F-PEI NPs) were employed to establish a model DCV with a certain degree of maturation and antigen cross-presentation due to the high efficiency of antigen delivery and cell compatibility [5c] (Figure 2G). OVA was mixed with F-PEI at a 1 : 1 weight ratio (pH = 7.0) to form OVA/F-PEI NPs with a hydrodynamic size at around 130 nm and zeta potential at around + 46 mV (Figure S8 and Table S2).…”

Administration sequence- and formation-dependent vaccination using acid-degradable polymeric nanoparticles with high antigen encapsulation capability

“…19–23 Their multifaceted function of efficient and facile encapsulation of antigens and intracellular release within APCs have been successfully employed for successful vaccination. 24–27 After uptake into APCs, exogenous protein antigens are degraded into peptides in endosomal compartments, which are in turn transported back to the cell surface by class II MHC molecules for recognition by antigen receptors of CD4 T cells. In contrast, the transport of peptides by class I MHC molecules for recognition by CD8 T cells requires entry or origination of the antigen in the cytoplasm.…”