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.