Abstract
Vaccination is the most successful and cost-effective method to prevent infectious diseases. However, many vaccine antigens have poor in vivo immunogenic potential and need adjuvants to enhance immune response. The application of systems biology to immunity and vaccinology has yielded crucial insights about how vaccines and adjuvants work. We have previously characterized two safe and powerful delivery systems derived from non-pathogenic prokaryotic organisms: E2 and fd filamentous bacteriophage systems. They elicit an in vivo immune response inducing CD8+ T-cell responses, even in absence of adjuvants or stimuli for dendritic cells’ maturation. Nonetheless, a systematic and comparative analysis of the complex gene expression network underlying such activation is missing. Therefore, we compared the transcriptomes of ex vivo isolated bone marrow-derived dendritic cells exposed to these antigen delivery systems. Significant differences emerged, especially for genes involved in innate immunity, co-stimulation, and cytokine production. Results indicate that E2 drives polarization toward the Th2 phenotype, mainly mediated by Irf4, Ccl17, and Ccr4 over-expression. Conversely, fd-scαDEC-205 triggers Th1 T cells’ polarization through the induction of Il12b, Il12rb, Il6, and other molecules involved in its signal transduction. The data analysis was performed using RNASeqGUI, hence, addressing the increasing need of transparency and reproducibility of computational analysis.
Highlights
In the last three decades, the rapid advances in vaccinology enabled us to prevent some of the major diseases that used to kill or incapacitate millions of children
Since adjuvants are added to vaccine formulations in order to enhance the magnitude—and modulate the quality—of the immune response, several studies have focused on the effect of adjuvants, combined with vaccines, and the possibility to have antigenic carriers endowed with adjuvant activity in new vaccine formulations is appealing [3]
We recently demonstrated that fd-scαDEC-205 is a powerful delivery system that induces CD8+ T cell responses even when administered in the absence of adjuvants or maturation stimuli for dendritic cells [14]
Summary
In the last three decades, the rapid advances in vaccinology enabled us to prevent some of the major diseases that used to kill or incapacitate millions of children. We established, and largely characterized, two innovative delivery systems derived from nonpathogenic prokaryotic organisms able to induce immune response in vivo: the E2 and the fd filamentous bacteriophage systems [4,5,6,7] The former is based on the use of the E2 protein of the pyruvate dehydrogenase complex of Bacillus stearothermophilus organized as a viral capsid structure. Sixty copies of recombinant E2 protein self-assemble to form a pentagonal dodecahedral scaffold with icosahedral symmetry It results in the formation of a large multimeric particle with a molecular weight >1.5 Mega Daltons and a diameter of approximately 24 nm. We recently demonstrated that fd-scαDEC-205 is a powerful delivery system that induces CD8+ T cell responses even when administered in the absence of adjuvants or maturation stimuli for dendritic cells [14]
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