Size-Dependent Antibacterial Immunity of Staphylococcus aureus Protoplast-Derived Particulate Vaccines

BACKGROUND: Vaccination provides a viable alternative to antibiotics for the treatment of drug-resistant bacterial infection. Bacterial protoplasts have gained much attention for a new generation vaccine due to depleting toxic outer wall components. PURPOSE: The objective of this study was to reveal the effects of bacterial protoplast-derived nanovesicles (PDNVs) size on antibacterial immunity. METHODS: Herein, we prepared bacterial PDNVs with different sizes by removing the cell wall of Staphylococcus aureus (S. aureus) to generate multi-antigen nanovaccines. Furthermore, we investigated the ability of PDNVs in different sizes to activate dendritic cells (DCs) and trigger humoral and cellular immune responses in vivo. RESULTS: We obtained particles of ∼200 nm, 400 nm, and 700 nm diameters and found that all the PDNVs readily induce efficient maturation of DCs in the draining lymph nodes of the vaccinated mice. Dramatically, the activation of DCs was increased with decreasing particle sizes. In addition, vaccination with PDNVs generated elevated expression levels of specific antibody and the production of INF-γ, especially the smaller ones, indicating the capability of inducing strong humoral immunity and Th1 biased cell responses against the source bacteria. CONCLUSION: These observed results provide evidence for size-dependent orchestration of immune responses of PDNVs and help to rationally design and develop effective antibacterial vaccines.