title: A potent adjuvant effect of a CD1d-binding NKT cell ligand in human immune system mice.
abstract: A CD1d-binding invariant natural killer T (iNKT)-cell stimulatory glycolipid, namely 7DW8-5, is shown to enhance the efficacy of radiation-attenuated sporozoites (RAS)-based malaria vaccine in mice. In the current study, we aim to determine whether 7DW8-5 can display a potent adjuvant effect in human immune system (HIS) mice.
  
  
  
  HIS-A2/hCD1d mice, which possess both functional human iNKT cells and CD8+ T cells, were generated by the transduction of NSG mice with adeno-associated virus serotype 9 expressing genes that encode human CD1d molecules and HLA-A*0201, followed by the engraftment of human hematopoietic stem cells. The magnitudes of human iNKT-cell response against 7DW8-5 and HLA-A*0201-restricted human CD8+ T-cell response against a human malaria antigen in HIS-A2/hCD1d mice were determined by using human CD1d tetramer and human HLA-A*0201 tetramer, respectively.
  
  
  
  We found that 7DW8-5 stimulates human iNKT cells in HIS-A2/hCD1d mice, as well as those derived from HIS-A2/hCD1d mice in vitro. We also found that 7DW8-5 significantly increases the level of a human malarial antigen-specific HLA-A*0201-restricted human CD8+ T-cell response in HIS-A2/hCD1d mice.
  
  
  
  Our study indicates that 7DW8-5 can display a potent adjuvant effect on RAS vaccine-induced anti-malarial immunity by augmenting malaria-specific human CD8+ T-cell response.
authors: a HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center , Affiliate of The Rockefeller University , New York , NY , USA.
authors: Xiangming
authors: X
authors: Li
authors: a HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center , Affiliate of The Rockefeller University , New York , NY , USA.
authors: Jing
authors: J
authors: Huang
authors: b Department of Medical Zoology , Mie University Graduate School of Medicine , Tsu , Mie , Japan.
authors: Izumi
authors: I
authors: Kaneko
authors: a HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center , Affiliate of The Rockefeller University , New York , NY , USA.|c Department of Pathology , New York University School of Medicine , New York , NY , USA.
authors: Min
authors: M
authors: Zhang
authors: b Department of Medical Zoology , Mie University Graduate School of Medicine , Tsu , Mie , Japan.
authors: Shiroh
authors: S
authors: Iwanaga
authors: b Department of Medical Zoology , Mie University Graduate School of Medicine , Tsu , Mie , Japan.
authors: Masao
authors: M
authors: Yuda
authors: a HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center , Affiliate of The Rockefeller University , New York , NY , USA.
authors: Moriya
authors: M
authors: Tsuji
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005699:Galactosylceramides / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D055611:Natural Killer T-Cells / Q000276:immunology*; D016896:Treatment Outcome; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
chemical_list: C000603808:7DW8-5 glycolipid; D000276:Adjuvants, Immunologic; D005699:Galactosylceramides; D017780:Malaria Vaccines; D015164:Vaccines, Inactivated
keywords: CD1d; Malaria; NKT cell; adjuvant; glycolipid; humanized mice; sporozoites