title: 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.
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.
authors.affiliation: 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.
authors.forename: Jordana G
authors.initials: JG
authors.lastname: Coelho-Dos-Reis
authors.affiliation: Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY 10016, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY 10016, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Tsao
authors.affiliation: Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY 10016, USA; Federal University of Sao Paulo, Sao Paulo 04021, Brazil.
authors.forename: Felipe V
authors.initials: FV
authors.lastname: Pereira
authors.affiliation: Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY 10016, USA.
authors.forename: Ryota
authors.initials: R
authors.lastname: Funakoshi
authors.affiliation: Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nakajima
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
authors.affiliation: Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY 10016, USA. Electronic address: mtsuji@adarc.org.
authors.forename: Moriya
authors.initials: M
authors.lastname: Tsuji
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D004357:Drug Synergism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005699:Galactosylceramides / Q000008:administration & dosage / Q000494:pharmacology*; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D007114:Immunization / Q000379:methods; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018448:Models, Immunological; D010455:Peptides / Q000276:immunology; D010967:Plasmodium yoelii / Q000276:immunology / Q000502:physiology; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000819:agonists* / Q000378:metabolism; D025721:WT1 Proteins / Q000235:genetics / Q000276:immunology
chemical_list: C000603808:7DW8-5 glycolipid; D018984:Epitopes, T-Lymphocyte; D005699:Galactosylceramides; D015789:HLA-A2 Antigen; D008050:Lipid A; D010455:Peptides; D020011:Protective Agents; D015800:Protozoan Proteins; D051197:Toll-Like Receptor 4; D025721:WT1 Proteins; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma; C048436:monophosphoryl lipid A
keywords: Adjuvant; CD1d; Cancer vaccine; Circumsporozoite protein; Glycolipid; Malaria vaccine; Memory-like effector NKT cells; NKT cells; TLR4; WT-1