Assessment of the current state of pharmaceutical development of anti-staphylococcal prophylactic drugs

Abstract

Infection caused by Staphylococcus aureus is the most common infection leading to the development of serious complications in humans. S. aureus is among the highly lethal bacteremia-associated pathogens with a mortality rate of approximately 18% in industrial countries; in developing countries, the rate is even higher, up to 27%. One of the most striking and challenging aspects of clinical manifestations caused by S. aureus is the ability of the bacterium to develop resistance to antibiotics. The development of alternative treatment options for staphylococcal infection is urgently needed. The use of immunotherapy and immunoprophylaxis to activate the anti-infection immune response in patients should be considered as a promising direction. Objective: to analyze the main trends in the development of vaccines aimed at the prevention of S. aureus infection and its virulence factors. The present review discusses vaccine development in recent years aimed at preventing infection caused by S. aureus. Particular attention is paid to pathogenicity factors (such as capsule, surface proteins and enzymes) that may be useful for the development of new candidate vaccines or immune therapeutics. In recent years, numerous clinical trials of candidate vaccines based on different antigens, taking into account particularly relevant S. aureus pathogenicity factors that influence morbidity, have not been successful due to their low efficacy or insufficiently substantiated safety (development of adverse events). One of the most important factors constraining vaccine development is the lack of successful translation of vaccine protective activity, which is observed in preclinical studies in experimental models but not confirmed in clinical trials. Therefore, according to numerous researchers, the use of multiple antigens in vaccine formulations should be considered with the focus on different mechanisms of S. aureus pathogenicity and the use of adjuvants.

Keywords

• anti-staphylococcal vaccines
• prophylaxis
• staphylococcal infections