Development of a Self-Adjuvanting Influenza Peptide-Glycolipid Conjugate Inducing CD8⁺ T-Cell Immunity

Effective immune activation against infectious diseases is achieved through the coordinated interplay of peptide antigen presentation and adjuvant-mediated stimulation, including lipid antigen-type adjuvants. For optimal immune activation with viral antigens, we applied covalent antigen-adjuvant complexation at the molecular level, which enables refined modulation of immune responses. This antigen-complex strategy was applied to viral peptide antigens containing sequence regions with lower variability, a particularly valuable approach for rapidly mutating viruses such as influenza. To construct these conjugated antigen complex structures, we used α-GalCer as the lipid antigen adjuvant and optimized linker designs that markedly influenced immunomodulatory activity. Using the precisely synthesized antigen complexes along with human leukocyte antigen (HLA)-transgenic mice, we successfully demonstrated selective immune activation, particularly the peptide antigen-specific CD8⁺ T cell expansion. These methods can  be extended to other viral antigens and may facilitate the development of CD8⁺ T cell-based self-adjuvanting conjugate vaccines.