Co-administration of α-GalCer Analog and TLR4 Agonist Induces Robust CD8(+) T-cell Responses to PyCS Protein and WT-1 Antigen and Activates Memory-like Effector NKT Cells

Overview

Journal Clin Immunol

Specialty Allergy & Immunology

Date 2016 May 2

PMID 27132023

Citations 11

Authors

Jordana G Coelho-Dos-Reis

Jing Huang

Tiffany Tsao

Felipe V Pereira

Ryota Funakoshi

Hiroko Nakajima

Haruo Sugiyama

Moriya Tsuji

Affiliations

Soon will be listed here.

Abstract

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(+)CD62L(-)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.

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