Co-administration of alpha-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

Co-administration of alpha-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 Coelho-dos-Reis, Jordana G. Google Scholar
Huang, Jing Google Scholar
Tsao, Tiffany Google Scholar
Pereira, Felipe V. Autor UNIFESP Google Scholar
Funakoshi, Ryota Google Scholar
Nakajima, Hiroko Google Scholar
Sugiyama, Haruo Google Scholar
Tsuji, Moriya Google Scholar
Abstract In the present study, the combined adjuvant effect of 7DW8-5, a potent alpha-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 yoelff, 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. (C) 2016 Elsevier Inc. All rights reserved.
Keywords Adjuvant
Glycolipid
NKT cells
CD1d
TLR4
Malaria vaccine
Cancer vaccine
WT-1
Circumsporozoite protein
Memory-like effector NKT cells
xmlui.dri2xhtml.METS-1.0.item-coverage San Diego
Language English
Sponsor NIH
Grant number NIH: AI070258
Date 2016
Published in Clinical Immunology. San Diego, v. 168, p. 6-15, 2016.
ISSN 1521-6616 (Sherpa/Romeo, impact factor)
Publisher Academic Press Inc Elsevier Science
Extent 6-15
Origin http://dx.doi.org/10.1016/j.clim.2016.04.014
Access rights Closed access
Type Article
Web of Science ID WOS:000380297600002
URI https://repositorio.unifesp.br/handle/11600/57659

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