Tuberculosis vaccine(Aeras Technologies LLC)

Tuberculosis (TB) is a major global health problem, and the development of effective and safe vaccines is urgently needed. CD8⁺ T-cells play an important role alongside CD4⁺ T-cells in the protective immune response against TB. pH-sensitive liposomes are hypothesized to boost CD8⁺ T-cell responses by promoting class I presentation through a mechanism involving pH-dependent endosomal escape and the cytosolic transfer of antigens. The aim of the study was to explore the potential of pH-sensitive liposomes as a novel delivery system for a multi-stage protein subunit vaccine against TB in primary human cells. The liposomes were formulated with the fusion antigen Ag85b-ESAT6-Rv2034 (AER), which was previously shown to be effective in reducing bacterial load in the lungs HLA-DR3 transgenic mice and guinea pigs. The liposomes were assessed in vitro for cellular uptake, cell viability, upregulation of cell surface activation markers, induction of cytokine production using human monocyte-derived dendritic cells (MDDCs), and activation of human antigen-specific T-cells. Liposome DOPC:DOPE:DOBAQ:EPC (3:5:2:4 M ratio) was effectively taken up, induced several cell surface activation markers, and production of CCl3, CCL4, and TNFα in MDDCs. It also induced upregulation of CD154 and IFNγ in T-cell clones in an antigen-specific manner. Thus, cationic pH-sensitive liposome-based TB vaccines have been demonstrated to be capable of inducing robust protective Mtb-specific immune responses, positioning them as promising candidates for effectiveTBvaccination.

Melanoma, caused by malignant melanocytes, is known for its invasiveness and poor prognosis. Therapies are often ineffective due to their heterogeneity and resistance. Bacillus Calmette-Guérin (BCG), primarily a tuberculosis vaccine, shows potential in treating melanoma by activating immune responses. In this study, data from The Cancer Genome Atlas and the National Center for Biotechnology Information Gene Expression Omnibus database were utilized to determine pivotal DEGs such as DSC2, CXCR1, BOK, and CSTB, which are significantly upregulated in BCG-treated blood samples and are strongly associated with the prognosis of melanoma. We employ tools like edgeR and ggplot2 for functional and pathway analysis and develop a prognostic model using LASSO Cox regression analysis to predict patient survival. A notable finding is the correlation between BCG-related genes and immune cell infiltration in melanoma, highlighting the potential of these genes as both biomarkers and therapeutic targets. Additionally, the study examines genetic alterations in these genes and their impact on the disease. This study highlights the necessity of further exploring BCG-related genes for insights into melanoma pathogenesis and treatment enhancement, suggesting that BCG's role in immune activation could offer novel therapeutic avenues in cancer treatment.