The Polymer Society of Korea

Abstract

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).