B CELL MULTIEPITOPE SENOVACCINE FOR HEALTHY AGING AND TACKLING AGE ASSOCIATED PATHOLOGIES

Abstract

Age-associated illnesses are a consequence of accumulating senescent cells within the body. These non-proliferative derivatives of normal cells evade cytotoxic immune clearance and supplement disease pathogenesis and aging. Since most senolytic drugs show short-lived, off-targeted effects with high toxicity, a search for a relatively safer and highly specific modality is warranted. A preemptive approach to stall the pathognomonic signs of aging can be achieved through prophylactics called senovaccines, that trigger the immune system to specifically target and eliminate the senescent cells. Characteristic cellular markers of senescent cells such as urokinase plasminogen activator receptor (uPAR) and glycoprotein nonmetastatic melanoma protein B (GPNMB) can be used as promising senoantigens for fabricating senovaccines. In this research, a novel B cell multiepitope senovaccine has been proposed that can potentially elicit a long-lasting humoral immune response. Five highly antigenic B-cell epitopes were predicted and combined with a built-in adjuvant beta-defensin using suitable linkers. The senovaccine construct fulfilled the criteria of nonallergenicity, nontoxicity, solubility and stability. Molecular docking and simulation analysis revealed that the senovaccine construct can form productive and stable complexes with the variable region of anti-uPAR antibody. The computationally designed B-cell multiepitope senovaccine provides us with a novel plausible model that can be explored further for the development of efficacious senovaccines that support healthy aging.