T-cell Subset Regulation in Atopy

Presentation of processed allergen by antigen-presenting cells to T-helper (Th) lymphocytes, which is influenced costimulatory signals, cytokines, chemokines, and regulatory T cells (Tregs), determines the development of different types of T-cell immunity. The discovery of Tregs revolutionized the primary concepts of immune regulation interpreted within the framework of a binary Th1/Th2 paradigm. Tregs play a central role in the maintenance of peripheral homeostasis, the establishment of controlled immune responses, and the inhibition of allergen-specific effector cells. Recently, some other T-cell subsets appeared, including Th17 and Th9 cells, which control local tissue inflammation through upregulation of proinflammatory cytokines and chemokines. This review aims to discuss our understanding of the T-cell subset reciprocal interaction in atopy

Immunological Principles Guiding the Rational Design of Particles for Vaccine Delivery

Despite the immense public health successes of immunization over the past century, effective vaccines are still lacking for globally important pathogens such as human immunodeficiency virus, malaria, and tuberculosis. Exciting recent advances in immunology and biotechnology over the past few decades have facilitated a shift from empirical to rational vaccine design, opening possibilities for improved vaccines. Some of the most important advancements include (i) the purification of subunit antigens with high safety profiles, (ii) the identification of innate pattern recognition receptors (PRRs) and cognate agonists responsible for inducing immune responses, and (iii) developments in nano- and microparticle fabrication and characterization techniques. Advances in particle engineering now allow highly tunable physicochemical properties of particle-based vaccines, including composition, size, shape, surface characteristics, and degradability. Enhanced collaborative efforts between researchers in immunology and materials science are expected to rise to next-generation vaccines. This process will be significantly aided by a greater understanding of the immunological principles guiding vaccine antigenicity, immunogenicity, and efficacy. With specific emphasis on PRR-targeted adjuvants and particle physicochemical properties, this review aims to provide an overview of the current literature to guide and focus rational particle-based vaccine design efforts

Physicochemical and Immunological Assessment of Engineered Pure Protein Particles with Different Redox States

The development of subunit antigen delivery formulations has become an important research endeavor, especially in cases where a whole cell vaccine approach has significant biosafety issues. Particle-based systems have shown particular efficacy due to their inherent immunogenicity. In some cases, fabrication techniques can lead to changes in the redox states of encapsulated protein antigens. By employing a uniform, well-characterized, single-protein system, it is possible to elucidate how the molecular details of particle-based protein antigens affect their induced immune responses. Using mesoporous silica-templated, amide bond-stabilized ovalbumin particles, three types of particles were fabricated from native, reduced, and oxidized ovalbumin, resulting in particles with different physicochemical properties and immunogenicity. Phagocytosis, transcription factor activation, and cytokine secretion by a mouse macrophage cell line did not reveal significant differences between the three types of particles. Oxidation of the ovalbumin, however, was shown to inhibit the intracellular degradation of the particles compared with native and reduced ovalbumin particles. Slow intracellular degradation of the oxidized particles was correlated with inefficient antigen presentation and insignificant levels of T cell priming and antibody production in vivo. In contrast, particles fabricated from native and reduced ovalbumin were rapidly degraded after internalization by macrophages in vitro and resulted in significant T cell and B cell immune responses in vivo. Taken together, the current study demonstrates how the redox state of a protein antigen significantly impacts the immunogenicity of the particulate vaccine formulations

Nanoscale engineering of low-fouling surfaces through polydopamine immobilisation of zwitterionic peptides

We report a versatile approach for the design of substrate-independent low-fouling surfaces via mussel-inspired immobilisation of zwitterionic peptides. Using mussel-inspired polydopamine (PDA) coatings, zwitterionic glutamic acid- and lysine-based peptides were immobilised on various substrates, including noble metals, metal oxides, polymers, and semiconductors. The variation of surface chemistry and surface wettability upon surface treatment was monitored with X-ray photoelectron spectroscopy (XPS) and water contact angle measurements. Following peptide immobilisation, the surfaces became more hydrophilic due to the strong surface hydration compared with PDA-coated surfaces. The peptide-functionalised surfaces showed resistance to human blood serum adsorption and also effectively prevented the adhesion of gram-negative and gram-positive bacteria (i.e., Escherichia coli and Staphylococcus epidermidis) and mammalian cells (i.e., NIH 3T3 mouse embryonic fibroblast cells). The versatility of mussel-inspired chemistry combined with the unique biological nature and tunability of peptides allows for the design of low-fouling surfaces, making this a promising coating technique for various applications

Role of the Protein Corona Derived from Human Plasma in Cellular Interactions between Nanoporous Human Serum Albumin Particles and Endothelial Cells

The presence of a protein corona on various synthetic nanomaterials has been shown to strongly influence how they interact with cells. However, it is unclear if the protein corona also exists on protein particles, and if so, its role in particle-cell interactions. In this study, pure human serum albumin (HSA) particles were fabricated via mesoporous silica particle templating. Our data reveal that various serum proteins adsorbed on the particles, when exposed to human blood plasma, forming a corona. In human umbilical vein endothelial cells (HUVECs), the corona was shown to decrease particle binding to the cell membrane, increase the residence time of particles in early endosomes, and reduce the amount of internalized particles within the first hours of exposure to particles. These findings reveal important information regarding the mechanisms used by vascular endothelial cells to internalize protein-based particulate materials exposed to blood plasma. The ability to control the cellular recognition of these organic particles is expected to aid the advancement of HSA-based materials for intravenous drug delivery

Differential Roles of the Protein Corona in the Cellular Uptake of Nanoporous Polymer Particles by Monocyte and Macrophage Cell Lines

Many biomolecules, mainly proteins, adsorb onto polymer particles to form a dynamic protein corona in biological environments. The protein corona can significantly influence particle-cell interactions, including internalization and pathway activation. In this work, we demonstrate the differential roles of a given protein corona formed in cell culture media in particle uptake by monocytes and macrophages. By exposing disulfide-stabilized poly(methacrylic acid) nanoporous polymer particles (PMASH NPPs) to complete cell growth media containing 10% fetal bovine serum, a protein corona, with the most abundant component being bovine serum albumin, was characterized. Upon adsorption onto the PMASH NPPs, native bovine serum albumin (BSA) was found to undergo conformational changes. The denatured BSA led to a significant decrease in internalization efficiency in human monocytic cells, THP-1, compared with the bare particles, due to reduced cell membrane adhesion. In contrast, the unfolded BSA on the NPPs triggered class A scavenger receptor-mediated phagocytosis in differentiated macrophage-like cells (dTHP-1) without a significant impact on the overall internalization efficiency. Taken together, this work demonstrates the disparate effects of a given protein corona on particle-cell interactions, highlighting the correlation between protein corona conformation in situ and relevant biological characteristics for biological functionalities