Biomaterials for Nanoparticle Vaccine Delivery Systems

Abstract

Subunit vaccination benefits from improved safety over attenuated or inactivated vaccines, but their limited capability to elicit long-lasting, concerted cellular and humoral immune responses is a major challenge. Recent studies have demonstrated that antigen delivery via nanoparticle formulations significantly improve immunogenicity of vaccines due to either intrinsic immunostimulatory properties of the materials or by co-entrapment of molecular adjuvants such as Toll-like receptor agonists. These studies have collectively shown that nanoparticles designed to mimic biophysical and biochemical cues of pathogens offer new exciting opportunities to enhance activation of innate immunity and elicit potent cellular and humoral immunity with minimal cytotoxicity. In this review, we present key research advances that were made within the last 5 years in the field of nanoparticle vaccine delivery systems. In particular, we focus on the impact of biomaterials composition, size, and surface charge of nanoparticles on modulation of particle biodistribution, delivery of antigens and immunostimulatory molecules, trafficking and targeting of antigen presenting cells, and overall immune responses in systemic and mucosal tissues. This review describes recent progresses in the design of nanoparticle vaccine delivery carriers, including liposomes, lipid-based particles, micelles and nanostructures composed of natural or synthetic polymers, and lipid-polymer hybrid nanoparticles.

Cationic liposomes promote antigen cross-presentation in dendritic cells by alkalizing the lysosomal pH and limiting the degradation of antigens

“…[1][2][3][4][5] However, the precise mechanisms of how CLs promote cross-presentation and cross-priming of antigen-specific CD8…”

“…Briefly, 5×10 4 BMDCs were pulsed with OVA in the presence or absence of various doses of liposomes or other reagents together with 1 μg/mL of MPLA (TLR4 agonist; Avanti Polar Lipids). After overnight culture, BMDCs were washed three times and coincubated with 5×10 4 naive OT-I CD8 + T-cells that were isolated from spleens from OT-I transgenic mice with a magnetic CD8 + T-cell-negative selection kit and prelabeled with 1 μM CFSE for 10 min at 37°C.…”

“…[1][2][3][4][5] Wide interest in CLs stems from their unique attributes, including their abilities to form nanocomplexes with anionic plasmid DNAs, peptides, and proteins; 1,2 to prolong antigen release at the site of injection (ie, depot effect); 6,7 to induce uptake by antigen-presenting cells (APCs) mediated by their ionic interaction with negatively charged cellular membranes; 1,8 and to allow the simultaneous delivery of antigen and adjuvant molecules to APCs, including B-cells, for the induction of IgG responses. [9][10][11] Importantly, CLs can also enhance antigen cross-presentation 12,13 -the process by which APCs phagocytose extracellular protein antigens, process them intracellularly into peptide epitopes, and present them in the context of major histocompatibility complex-I (MHC-I) on the The specialized role of DCs in cross-presentation is supported by their unique characteristics, including their mildly degradative phagosomes compared to those of other phagocytic cells, such as macrophages; shuttling of endosomal protein antigens to the cytosol for subsequent processing via proteasomes for antigen degradation; and efficient loading of the processed antigen peptides onto MHC-I molecules via either endoplasmic reticulum (ER) or vacuolar endosomal pathways.…”

Bile salts-containing vesicles: promising pharmaceutical carriers for oral delivery of poorly water-soluble drugs and peptide/protein-based therapeutics or vaccines

“…The stability imposed by BS-vesicles was attributed to the repulsion between the bile salts already present in the vesicle bilayer and the intestinal bile salts in the GIT (Conacher et al, 2001). Hence, providing protection for the entrapped agents from the hostile environment in the GIT (Beg et al, 2013;Sahdev et al, 2014) (Figure 2). Different ingredients utilized in the preparation of BS-vesicles are collectively listed in Table 1.…”

Untitled

“…response. Nanoparticles have been extensively investigated and widely reported over the past three decades as delivery vehicles or as nanocarriers (as they currently referred to) of traditional chemotherapeutics targeted to solid tumours [7][8][9]. A wide span of nanoparticles, such as metallic nanoparticles, antigens conjugated to or associated with metallic nanoparticles, polymer based micelle, dendrimers, liposomes, DNA vaccines, carbon nanotubes, buckminsterfullerene, etc., have been investigated.…”