Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
ISSN: 2155-9899
Sandra Lazzaro, Cinzia Giovani, Simona Mangiavacchi, Barbara Baudner, Domenico Maione, Andrew J Geall, Ennio De Gregorio, Ugo D?Oro and Cecilia Buonsanti
Accepted Abstracts: J Clin Cell Immunol
SAM® vaccines are self-amplifying mRNA derived from the positive-strand alphavirus genome. They contain genes encoding non structural proteins which drive the RNA replication, but lack the viral structural proteins which are replaced by vaccine antigens.In this way; RNA amplification within the cytoplasm of transfected cells allows an increase of antigen expression. In addition, dsRNA intermediates exert an intrinsic adjuvant effect resulting in the induction of enhanced immune responses. It has been shown that SAM® vaccines are effective at eliciting both humoral and cellular antigen-specific immune responses in animal models of infectious and non-infectious diseases. However their mechanism of action has not been fully elucidated. To date, no evidence of in vivo transduction of APCs by the SAM® vectors has been produced, while the antigen expression has been shown to occur mostly in the muscle fibers. Bone marrow chimeric mice were used to assess the respective contribution of muscle cells and bone marrow derived antigen presenting cells (APCs) to CD8 T cells priming following SAM®vaccination. Our results show that bone marrow derived APCs rather than muscle cells are responsible for direct induction of Class-I restricted CD8 T cells. Nevertheless, direct transfection of APCs by SAM® vectors is it not required for CD8 T cells priming, suggesting that the antigen is expressed within muscle cells and then presentedby professional bone marrow derived APC to CD8 T cells, most likely through a cross-priming.
Sattva S Neelapu is currently a tenured Associate Professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. He completed his medical school at Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India and Clinical Fellowship in Medical Oncology and Postdoctoral Fellowship in Tumor Immunology and Immunotherapy at the National Cancer Institute, National Institutes of Health, Bethesda, Maryland. His research is focused on characterization of immunoregulatory mechanisms in the tumor microenvironment in patients with lymphoma and developing strategies to target them.