Immunopeptidomics analysis of human atherosclerosis plaques identifies antigenic drivers of atherosclerosis.

Background And Aim: Atherosclerosis has an auto-immune component driven by self-reactive T and B cells. Identifying their antigenic drivers may lead to new diagnosis and treatment approaches. Here, we aim to identify immunogenic T cell epitopes derived from atherosclerosis-relevant proteins such as ApoB100 by studying the repertoire of peptides presented by HLA in human plaques.

In vitro and in vivo evaluation of clinically-approved ionizable cationic lipids shows divergent results between mRNA transfection and vaccine efficacy.

Ionizable cationic lipids (ICLs) play an essential role in the effectiveness of lipid nanoparticles (LNPs) for delivery of mRNA therapeutics and vaccines; therefore, critical evaluations of their biological performance would extend the existing knowledge in the field. In the present study, we examined the effects of the three clinically-approved ICLs, Dlin-MC3-DMA, ALC-0315 and SM-102, as well as DODAP, on the in vitro and in vivo performance of LNPs for mRNA delivery and vaccine efficacy. mRNA-LNPs containing these lipids were successfully prepared, which were all found to be very similar in their physicochemical properties and mRNA encapsulation efficiencies.

The Use of a Staggered Herringbone Micromixer for the Preparation of Rigid Liposomal Formulations Allows Efficient Encapsulation of Antigen and Adjuvant.

Anionic liposomal formulations have previously shown to have intrinsic tolerogenic capacity and these properties have been related to the rigidity of the particles. The combination of highly rigid anionic liposomes to deliver tolerogenic adjuvants and antigen peptides has potential applications for the treatment of autoimmune and inflammatory diseases. However, the preparation of these highly rigid anionic liposomes using traditional methods such as lipid film hydration presents problems in terms of scalability and loading efficiency of some costly tolerogenic adjuvants like 1-α,25-dihydroxyvitaminD3.

High-affinity antigen association to cationic liposomes via coiled coil-forming peptides induces a strong antigen-specific CD4 T-cell response.

Liposomes are widely investigated as vaccine delivery systems, but antigen loading efficiency can be low. Moreover, adsorbed antigen may rapidly desorb under physiological conditions. Encapsulation of antigens overcomes the latter problem but results in significant antigen loss during preparation and purification of the liposomes.

Atomic force microscopy measurements of anionic liposomes reveal the effect of liposomal rigidity on antigen-specific regulatory T cell responses.

Regulatory T cells (Tregs) are vital for maintaining a balanced immune response and their dysfunction is often associated with auto-immune disorders. We have previously shown that antigen-loaded anionic liposomes composed of phosphatidylcholine (PC) and phosphatidylglycerol (PG) and cholesterol can induce strong antigen-specific Treg responses. We hypothesized that altering the rigidity of these liposomes while maintaining their size and surface charge would affect their capability of inducing Treg responses.

CD39 identifies a microenvironment-specific anti-inflammatory CD8 T-cell population in atherosclerotic lesions.

Background And Aims: CD8 T-cells have been attributed both atherogenic and atheroprotective properties, but analysis of CD8 T-cells has mostly been restricted to the circulation and secondary lymphoid organs. The atherosclerotic lesion, however, is a complex microenvironment containing a plethora of inflammatory signals, which may affect CD8 T-cell activation. Here, we address how this environment affects the functionality of CD8 T-cells.

Anionic 1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG) liposomes induce antigen-specific regulatory T cells and prevent atherosclerosis in mice.

Atherosclerosis is the predominant underlying pathology of many types of cardiovascular disease and is one of the leading causes of death worldwide. It is characterized by the retention of oxidized low-density lipoprotein (ox-LDL) in lipid-rich macrophages (foam cells) in the intima of arteries. Autoantigens derived from oxLDL can be used to vaccinate against atherosclerosis.

Orchestrating immune responses: How size, shape and rigidity affect the immunogenicity of particulate vaccines.

Particulate carrier systems are promising drug delivery vehicles for subunit vaccination as they can enhance and direct the type of T cell response. In order to develop vaccines with optimal immunogenicity, a thorough understanding of parameters that could affect the strength and quality of immune responses is required. Pathogens have different dimensions and stimulate the immune system in a specific way.