SA-4-1BBL as a platform to develop adjuvant systems for prophylactic and therapeutic vaccines.

SA-4-1BBL;Adjuvants;Vaccine;Plague;Breast cancer

Gunes Dinc, 1984-

University:University of Louisville

Department:Microbiology and Immunology

关键词: SA-4-1BBL;    Adjuvants;    Vaccine;    Plague;    Breast cancer;   

Others  :  https://ir.library.louisville.edu/cgi/viewcontent.cgi?article=1349&context=etd

美国|英语

来源: The Universite of Louisville's Institutional Repository

【 摘 要 】

Vaccines against infectious diseases are one of the most critical accomplishments in modern medicine. Despite significant progress in vaccinology, there is still a dire need for developing vaccines against various acute and chronic infections and cancer. In general, vaccines are categorized as prophylactic, given to healthy individuals to prevent disease, and therapeutic, administered to people who already have disease. As such, the nature, quality, and quantity of immune responses required for the efficacy of these two types vaccines are different. Prophylactic vaccines against infectious diseases primarily rely on the generation of neutralizing high titers of antibody for their efficacy. These vaccines are generally effective because they target a host with an unaltered and competent immune system. In marked contrast, the efficacy of therapeutic vaccines has been a major challenge since they are administered into a host with a compromised immune system. Therapeutic vaccines need not only to generate effective adaptive cellular, particularly CD8+ T cell, immune responses to chronic infection and cancer, but they also need to overcome various immune evasion mechanisms employed by infection and progressing tumor. For both types of vaccines, the generation of a long-lasting adaptive immunity is the key. Historically, prophylactic vaccines against infections were made from live-attenuated or inactivated forms of the microbes, but there were concerns about stability, side effects and safety of such vaccines. Advancements in molecular biology and DNA technologies led to the development of recombinant subunit vaccine with well-defined antigens. In particular, vaccines based on recombinant proteins present an attractive approach because of their ease of production, storage, distribution, and safety profiles. However, recombinant protein based subunit vaccines are poorly immunogenic and require adjuvants for efficacy. Most of the adjuvants that have been approved for clinical use, and those under development primarily target innate arm of the immune system for the generation of subsequent adaptive immunity. Key to the initiation of adaptive immune responses is the interactions between an APC and T cells and acquisition of 3 distinct singles by T cells. Signal 1 is delivered by the interaction of TCR on T cells with an MHC/peptide complex on APC. This signal is then qualified by costimulatory receptor ligand interaction on the APC and T cells, providing signal 2. Signal 3 is provided by various cytokines elaborated by activated APCs and T cells and critical for the expansion of the immune response. The lack of costimulation during these interactions results in