IgM-functionalized biomimetic nanovaccine for immunological activation and bacterial toxin neutralization

Pore-forming toxins (PFTs) are exotoxins secreted by bacteria that aggregate and perforate cell membranes through mechanisms such as binding to specific membrane proteins, thereby killing cells and promoting bacterial invasion, migration, and proliferation. In this study, an anti-virulence factor strategy and vaccine were combined to develop folic acid-modified red blood cell membrane-hybrid liposomes (FA-RCM-Lips). By utilizing the aggregation and perforation mechanism of pore-forming toxins on red blood cell membranes, Vibrio vulnificus hemolysin A (VvhA) was efficiently loaded as the antigenic protein, thereby neutralizing the toxicity of the toxin while maximizing the retention of its antigenic activity and constructing a toxoid nanovaccine (FA-RCM-Lips(VvhA)). The nanocarrier served as an adjuvant to enhance antigen uptake by antigen-presenting cells, while folic acid molecules adsorbed natural IgM, enhancing antigen uptake and presentation by B cells through the IgM-complement pathway. FA-RCM-Lips reduced the hemolysis rate of VvhA by 98.78 % and simultaneously inhibited VvhA-induced skin and tissue toxicity. Subcutaneous and intravenous immunization with FA-RCM-Lips(VvhA) induced stronger IgG titers, improved antigen presentation, enhanced immune responses, and provided immunoprotection in mice.