Nano-liposomal Vaccine Delivery Systems for Enhancing Cell-Mediated Immunity against Staphylococcus aureus: Current Progress, Preclinical Advances, and Future Perspectives

Abstract

1. aureus is one of the most clinically important bacterial pathogens due to its ability to survive in host immune systems, cause persistent infection and easily acquire antimicrobial resistance. The spread of methicillin-resistant Staphylococcus aureus (MRSA) worldwide has underscored the critical need for MRSA vaccines with sustained protection that surpasses the action of existing antibiotics. Although much research has been conducted over the years, previous vaccine candidates have shown limited clinical success, mostly due to the failure to generate strong enough cell-mediated immunity for bacterial clearance. With the advancement of nanotechnology, Nanoliposomes have emerged as one of the most promising systems for vaccine delivery due to their superior biocompatibility, high antigen loading capacity, controlled release characteristics and their ability to improve the antigen presentation by the professional antigen presenting cells. Optimised physicochemical properties, such as particle size, lipid composition, surface charge, membrane stability and incorporation of adjuvants, enable nanoliposomal vaccines to effectively activate innate and adaptive immune responses and generate a balanced activation of Th1 and Th17 lymphocytes, which is critical for protective immunity against S. aureus.

The present review gives a detailed and critical description of what is known about the host immune responses to staphylococci with special focus on the mechanisms involved in cellular immunity and antigen presentation. In addition, the structural properties, physicochemical properties, immunomodulatory mechanisms, formulation strategies, and considerations of nanoliposomal vaccine delivery systems are discussed. Representative preclinical studies are comparatively analyzed to understand the key formulation parameters that shape vaccine efficacy and current formulation challenges for vaccine manufacturing, stability, safety and clinical translation are critically examined. Other innovative technologies, such as multifunctional Nanoliposomes, nucleic acid (mRNA) vaccines, targeted delivery systems, systems immunology, and artificial intelligence in vaccine design are also mentioned as potential pathways for next-generation antibacterial vaccines.

Covering topics such as Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus (MRSA), Nanoliposomes, Vaccine delivery systems, Cell-mediated immunity, Th1 and Th17 responses, Nano vaccines, Antigen presentation.