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https://www.arca.fiocruz.br/handle/icict/23941
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ArtigoDireito Autoral
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Objetivos de Desenvolvimento Sustentável
03 Saúde e Bem-EstarColeções
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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.
Glycolipid
NKT cells
CD1d
TLR4
Malaria vaccine
Cancer vaccine
WT-1
Circumsporozoite protein
Memory-like effector NKT cells
Autor(es)
Afiliação
Rockefeller University. Aaron Diamond AIDS Research Center. New York, NY, USA / Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil.
Rockefeller University. Aaron Diamond AIDS Research Center.
Rockefeller University. Aaron Diamond AIDS Research Center.
Rockefeller University. Aaron Diamond AIDS Research Center. New York, NY, USA/Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil.
Rockefeller University. Aaron Diamond AIDS Research Center. New York, NY.
Osaka University Graduate School of Medicine. Department of Cancer Immunology. Osaka, Japan.
Osaka University Graduate School of Medicine. Department of Functional Diagnostic Science. Osaka, Japan.
Rockefeller University. Aaron Diamond AIDS Research Center.
Rockefeller University. Aaron Diamond AIDS Research Center.
Rockefeller University. Aaron Diamond AIDS Research Center.
Rockefeller University. Aaron Diamond AIDS Research Center. New York, NY, USA/Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil.
Rockefeller University. Aaron Diamond AIDS Research Center. New York, NY.
Osaka University Graduate School of Medicine. Department of Cancer Immunology. Osaka, Japan.
Osaka University Graduate School of Medicine. Department of Functional Diagnostic Science. Osaka, Japan.
Rockefeller University. Aaron Diamond AIDS Research Center.
Resumo em Inglês
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+ Tcell 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.
Palavras-chave em inglês
AdjuvantGlycolipid
NKT cells
CD1d
TLR4
Malaria vaccine
Cancer vaccine
WT-1
Circumsporozoite protein
Memory-like effector NKT cells
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