Membrane Anchoring of Alpha-Hemolysin onto pH-Responsive Lipid Nanovaccine for an Effective Staphylococcus aureus Vaccine
발표자
배수민 (카이스트)
연구책임자
남윤성 (카이스트)
공동저자
배수민 (카이스트), 남윤성 (카이스트)
초록
내용
Despite the clinical need, developing an effective vaccine against S. aureus remains challenging. Alpha-hemolysin (Hla), a pore-forming toxin, is a key virulent factor that serves as a promising vaccine antigen. Here we developed a pH-responsive lipid nanovesicle (LNVs) platform designed to neutralize Hla toxicity while improving its immunogenicity through membrane anchoring. The LNVs were formulated using DPPC and cholesterol as a scaffold where Hla is inserted via specific PC-clamp interactions, with CHEMS and DOPE incorporated to confer pH sensitivity and promote endosomal escape. Consequently, the LNVs demonstrated efficient membrane fusion under endosome-mimicking conditions. Hla-anchored LNVs activated BMDCs, inducing the upregulation of CD40, CD80, CD86, and MHC Class II. These results indicate protein-anchored, pH-responsive LNVs as a potent and versatile vaccine platform against S. aureus infections. Funding: NRF grant funded by the Korea government (MSIT) (RS-2025-00516761).