Polymeric nanogels as vaccine delivery systems

Polymeric nanogels find a relevant field of application in the formulation of a new generation of therapeutic and preventive vaccines, aiming at the fine-tuned modulation of the immune response. Intrinsic properties of polymeric nanogels, such as material chemistry, size and shape, surface charge, and hydrophobicity or hydrophilicity, may be determining factors in shaping the induced immune response. These materials can thus work as synthetic adjuvants, which can also be conjugated with immunostimulants. Polymeric nanogels protect vaccine antigens from degradation in vivo and, surface-conjugated with antibodies or specific ligands, could increase active targeting specificity. This review covers the recent published data concerning the modulation of innate and adaptive immune responses by engineered polymeric nanogels and their potential application as delivery systems in vaccination.From the Clinical EditorIn this review, the utility of polymeric nanogels is discussed as adjuvants and protective agents for enhanced vaccination with more robust immune response and a more uniform outcome.

Graphical AbstractVaccination antigens (Ag), e.g., purified proteins, may be internalized by antigen-presenting cells (APC) from the external millieu by phagocytosis or other endocytic processes (1). Within endocytic compartments (EC), antigen is processed at acidic pH into peptide fragments (pt) (2). Peptides are then loaded to major histocompatibility complex (MHC) class II molecules (MHC II) transported into endocytic compartments in Golgi apparatus (Golgi)-originated vesicles (3). Mature endosomes fuse with the plasma membrane where peptides loaded to MHC class II molecules are exposed. Antigens may also be delivered to the cytosol and cleaved within the proteasome (Prt) originating peptides (4). These are transported into the endoplasmic reticulum (ER) where they are loaded to MHC class I molecules (MHC I) in a chaperone-assisted process (5). Peptide-loaded MHC class I molecules are transported to the cell membrane (6), where they can be recognized by specific CD8+ T-cells, whereas CD4+ T-cells recognize peptides presented in the context of MHC class II molecules (7). APC also provide co-stimulatory stimuli by either surface molecules (8) or soluble factors such as cytokines (9).Figure optionsDownload high-quality image (137 K)Download as PowerPoint slide