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Clin Immunol. 2016 Jul;168:6-15. doi: 10.1016/j.clim.2016.04.014. Epub 2016 Apr 27.

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.

Author information

1
Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY 10016, USA; Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, Minas Gerais 30192, Brazil. Electronic address: jordana.reis@cpqrr.fiocruz.br.
2
Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY 10016, USA.
3
Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY 10016, USA; Federal University of Sao Paulo, Sao Paulo 04021, Brazil.
4
Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
5
Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
6
Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY 10016, USA. Electronic address: mtsuji@adarc.org.

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.

KEYWORDS:

Adjuvant; CD1d; Cancer vaccine; Circumsporozoite protein; Glycolipid; Malaria vaccine; Memory-like effector NKT cells; NKT cells; TLR4; WT-1

PMID:
27132023
PMCID:
PMC4940295
DOI:
10.1016/j.clim.2016.04.014
[Indexed for MEDLINE]
Free PMC Article

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