Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6087023 | Clinical Immunology | 2016 | 10 Pages |
â¢7DW8-5, α-GalCer analog, and MPLA, a TLR4 agonist, have a combined adjuvant effect.â¢Co-injection of 7DW8-5 with MPLA augments peptide-specific CD8 + T-cell response.â¢7DW8-5 and MPLA together enhance protective immunity against malaria and cancer.â¢Co-injection of 7DW8-5 with MPLA induces activation of memory-like effector NKT cells.
In the present study, the combined adjuvant effect of 7DW8-5, a potent α-GalCer-analog, and monophosphoryl lipid A (MPLA), a TLR4 agonist, on the induction of vaccine-induced CD8+ T-cell responses and protective immunity was evaluated. Mice were immunized with peptides corresponding to the CD8+ T-cell epitopes of a malaria antigen, a circumsporozoite protein of Plasmodium yoelii, and a tumor antigen, a Wilms Tumor antigen-1 (WT-1), together with 7DW8-5 and MPLA, as an adjuvant. These immunization regimens were able to induce higher levels of CD8+ T-cell responses and, ultimately, enhanced levels of protection against malaria and tumor challenges compared to the levels induced by immunization with peptides mixed with 7DW8-5 or MPLA alone. Co-administration of 7DW8-5 and MPLA induces activation of memory-like effector natural killer T (NKT) cells, i.e. CD44+ CD62Lâ NKT cells. Our study indicates that 7DW8-5 greatly enhances important synergistic pathways associated to memory immune responses when co-administered with MPLA, thus rendering this combination of adjuvants a novel vaccine adjuvant formulation.