Microsomal membranes from antigen presenting cells present antigenic peptides to T cells: a novel approach in vaccine development.

PhDThe study of the immune system has provided insight in the mechanism of protection induced by vaccination; primarily that most clinically protective vaccines are potent in generating neutralizing antibody responses. Nonetheless, vaccination fails to protect against a wide range of acquired chronic infections caused by viruses, such as HIV and HCV, other intracellular pathogens, and cancer. Attempts to combat these diseases are thought to require the induction of the cellular arm of the immune response, in which dendritic cells (DCs) play a key role. Thus, DCs are now considered a promising target/tool when designing new-generation vaccines. Although mature DCs have the capacity to induce effective primary and secondary immune responses in vivo, their use in vaccination strategies is associated with several difficulties; for example, there are limitations involved in the loading of antigen, and in the appropriate maturation of DC in vitro. In this study, we have explored the hypothesis that the use of ERenriched microsomes isolated from professional antigen presenting cells, such as DCs, can represent an alternative vaccination strategy to those using live DCs. Endoplasmic reticulum-enriched microsomal membranes (microsomes) isolated from DCs contained high levels of peptide-receptive major histocompatibility complex (MHC) and co-stimulatory molecules. After loading with defined antigenic peptides, injected microsomes mediated MHC class I- and MHC class II-restricted T cell responses. The microsomal vaccine described and discussed in this thesis protects from a viral infection and was shown to regress an established murine tumor. Therefore, it could represent an exciting new alternative to currently available vaccine strategies

Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19

Whereas pathogen-specific T and B cells are a primary focus of interest during infectious disease, we have used COVID-19 to ask whether their emergence comes at a cost of broader B cell and T cell repertoire disruption. We applied a genomic DNA-based approach to concurrently study the immunoglobulin-heavy (IGH) and T cell receptor (TCR) β and δ chain loci of 95 individuals. Our approach detected anticipated repertoire focusing for the IGH repertoire, including expansions of clusters of related sequences temporally aligned with SARS-CoV-2–specific seroconversion, and enrichment of some shared SARS-CoV-2–associated sequences. No significant age-related or disease severity–related deficiencies were noted for the IGH repertoire. By contrast, whereas focusing occurred at the TCRβ and TCRδ loci, including some TCRβ sequence–sharing, disruptive repertoire narrowing was almost entirely limited to many patients aged older than 50 y. By temporarily reducing T cell diversity and by risking expansions of nonbeneficial T cells, these traits may constitute an age-related risk factor for COVID-19, including a vulnerability to new variants for which T cells may provide key protection