Conserved Influenza Epitopes Delivered via MHC-I-Functionalized Nanocarriers Induce Influenza-Specific CTL Responses

Seasonal influenza evades vaccine-induced immunity via ongoing antigenic drift, highlighting the critical necessity for universal vaccines that elicit broadly cross-reactive CD8⁺ T cell responses targeting conserved internal viral epitopes. In pursuit of this objective, we prepared biocompatible and biodegradable poly(lactic-co-glycolic acid) (PLGA) nanocarriers (NCs) and functionalized them with MHC-I molecules. Among various murine and human epitopes tested, PB1_703-711 and M1_58-66 showed the highest stabilization of H-2K^b and HLA-A2.1 molecules, respectively, thereby promoting sustained Ag presentation. These NCs exhibited specific peptide-loading onto MHC-I molecules while minimizing non-specific peptide surface binding. In vivo immunization of C57BL/6 mice with PB1_703-711-loaded NCs elicited epitope-specific CD8⁺ T cell responses. Furthermore, the successful specific peptide-loading of HLA-A2.1-attached NCs highlighted the system's human translational applicability. Ultimately, by combining effective Ag delivery with specific CTL induction, this designed NC platform provides a promising strategy for developing next-generation universal vaccines.