Finding the optimal combination between a given synthetic
peptide and an adjuvant opens an unlimited clinical potential for these vaccines, because if adequate epitopes were identified for a certain disease, antigens could be synthesized on demand. For this reason, successful adjuvants need to be safe and well tolerated, simply produced and with MI-773 ic50 inexpensive compounds, Inhibitors,research,lifescience,medical biodegradables, compatibles with many different antigens, and capable of function as a delivery system and immune potentiators [9]. Therefore, for licensing of new or newly formulated vaccines, nonclinical and clinical data regarding safety and efficacy are required, next to pharmaceutical quality data. These data are needed on the active ingredients, as well as the adjuvants and delivery systems, and their combination in the final product [10]. In this regard, there is only one guideline specifically dedicated to peptides, Guidance for Industry for the Submission of Chemistry, Manufacturing, and Controls Information for Synthetic Peptide Substances, published Inhibitors,research,lifescience,medical in 1994 [11], which stipulates the lot release specifications (sufficient to ensure the identity, purity, and Inhibitors,research,lifescience,medical strength of the peptide and demonstrate lot-to-lot consistency). The need of eliciting both humoral and cellular immune responses has limited the efficacy against certain pathogens, such as malaria and HIV [3]. Activating the cytolytic immune response
(CTL) is needed in the case of intracellular pathogens or tumors, and it is mediated by CD8 T cells, CD4 Th1 cells and natural killer T cells. Dendritic cells (DCs) have several innate features that make them ideal targets for vaccination purposes. They Inhibitors,research,lifescience,medical can
capture antigens that enter the body and move to the T cell areas of lymphoid organs to find the right clones and start the immune response [10]. In peripheral tissues, DCs are found in an immature stage specialized in capturing foreign antigens. Inhibitors,research,lifescience,medical In response to microbes, DCs undergo a process of maturation into antigen-presenting cells (APCs). Meanwhile, they migrate from the periphery to the draining lymph nodes, where they present antigens to the T lymphocytes. DCs can present peptides to the T cells in the context of major histocompatibility complex (MHC) classes I and II molecules and next also glycolipids and glycopeptides to T cells and NKT cells as well as polypeptides to B cells [12]. In order to achieve a CTL response, cytolytic cells must specifically recognize pathogen-derived antigens presented in MHC class I or in the CD1-lipid complex. Upon antigen recognition, immune cells release cytolytic agents that directly destroy infected cells and can induce inflammatory reactions which facilitate innate immune clearance and the development of some humoral response. In order to generate CD8+ T cell immune responses cross-presentation have to occur, in which an exogenous antigen is presented into MHC I molecules in order to promote strong cytolytic and Th1 inflammatory bias [3].
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