Single-Cell Analysis of Antigen-Specific CD8+ T-Cell Transcripts Reveals Profiles Specific to mRNA or Adjuvanted Protein Vaccines.

CD8+ T cells play a key role in mediating protective immunity after immune challenges such as infection or vaccination. Several subsets of differentiated CD8+ T cells have been identified, however, a deeper understanding of the molecular mechanism that underlies T-cell differentiation is lacking. Conventional approaches to the study of immune responses are typically limited to the analysis of bulk groups of cells that mask the cells' heterogeneity (RNA-seq, microarray) and to the assessment of a relatively limited number of biomarkers that can be evaluated simultaneously at the population level (flow and mass cytometry). Single-cell analysis, on the other hand, represents a possible alternative that enables a deeper characterization of the underlying cellular heterogeneity. In this study, a murine model was used to characterize immunodominant hemagglutinin (HA533-541)-specific CD8+ T-cell responses to nucleic- and protein-based influenza vaccine candidates, using single-cell sorting followed by transcriptomic analysis. Investigation of single-cell gene expression profiles enabled the discovery of unique subsets of CD8+ T cells that co-expressed cytotoxic genes after vaccination. Moreover, this method enabled the characterization of antigen specific CD8+ T cells that were previously undetected. Single-cell transcriptome profiling has the potential to allow for qualitative discrimination of cells, which could lead to novel insights on biological pathways involved in cellular responses. This approach could be further validated and allow for more informed decision making in preclinical and clinical settings.

Vaccines targeting angiogenesis in melanoma.

Angiogenesis has a significant role in metastasis and progression of melanoma. Even small tumors may be susceptible to metastasis and hence lead to a worse outcome in patients with melanoma. One of the anti-angiogenic treatment approaches that is undergoing comprehensive study is specific immunotherapy. While tumor cells are challenging targets for immunotherapy due to their genetic instability and heterogeneity, endothelial cells (ECs) are genetically stable. Therefore, vaccines targeting angiogenesis in melanoma are appropriate choices that target both tumor cells and ECs while capable of inducing strong, anti-tumor immune responses with limited toxicity. The main targets of angiogenesis are VEGFs and their receptors but other potential targets have also been investigated, especially in preclinical studies. Various types of vaccines that target angiogenesis in melanoma have been studied including DNA, peptide, protein, dendritic cell-based, and endothelial cell vaccines. This review outlines a number of target antigens that are important for potential progress in developing vaccines for targeting angiogenesis in melanoma. We also discuss different types of vaccines that have been investigated, delivery mechanisms and popular adjuvants, and suggest ways to improve future clinical outcomes.