title: Human CD8+ T cells mediate protective immunity induced by a human malaria vaccine in human immune system mice.
abstract: A number of studies have shown that CD8+ T cells mediate protective anti-malaria immunity in a mouse model. However, whether human CD8+ T cells play a role in protection against malaria remains unknown. We recently established human immune system (HIS) mice harboring functional human CD8+ T cells (HIS-CD8 mice) by transduction with HLA-A∗0201 and certain human cytokines using recombinant adeno-associated virus-based gene transfer technologies. These HIS-CD8 mice mount a potent, antigen-specific HLA-A∗0201-restricted human CD8+ T-cell response upon immunization with a recombinant adenovirus expressing a human malaria antigen, the Plasmodium falciparum circumsporozoite protein (PfCSP), termed AdPfCSP. In the present study, we challenged AdPfCSP-immunized HIS-CD8 mice with transgenic Plasmodium berghei sporozoites expressing full-length PfCSP and found that AdPfCSP-immunized (but not naïve) mice were protected against subsequent malaria challenge. The level of the HLA-A∗0201-restricted, PfCSP-specific human CD8+ T-cell response was closely correlated with the level of malaria protection. Furthermore, depletion of human CD8+ T cells from AdPfCSP-immunized HIS-CD8 mice almost completely abolished the anti-malaria immune response. Taken together, our data show that human CD8+ T cells mediate protective anti-malaria immunity in vivo.
authors: HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, 455 First Avenue, New York, NY 10016, United States.
authors: Xiangming
authors: X
authors: Li
authors: HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, 455 First Avenue, New York, NY 10016, United States.
authors: Jing
authors: J
authors: Huang
authors: HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, 455 First Avenue, New York, NY 10016, United States; Department of Pathology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, United States.
authors: Min
authors: M
authors: Zhang
authors: HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, 455 First Avenue, New York, NY 10016, United States.
authors: Ryota
authors: R
authors: Funakoshi
authors: Malaria Vaccine Development Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United States.
authors: Dutta
authors: D
authors: Sheetij
authors: Università degli Studi di Perugia, Perugia, Italy.
authors: Roberta
authors: R
authors: Spaccapelo
authors: Imperial College London, London, UK.
authors: Andrea
authors: A
authors: Crisanti
authors: Department of Pathology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, United States.
authors: Victor
authors: V
authors: Nussenzweig
authors: Department of Pathology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, United States; Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, NY, United States.
authors: Ruth S
authors: RS
authors: Nussenzweig
authors: HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, 455 First Avenue, New York, NY 10016, United States. Electronic address: mtsuji@adarc.org.
authors: Moriya
authors: M
authors: Tsuji
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000229:Dependovirus; D005822:Genetic Vectors; D015789:HLA-A2 Antigen / Q000235:genetics; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D010963:Plasmodium falciparum; D015800:Protozoan Proteins / Q000276:immunology; D034101:Sporozoites
chemical_list: C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan
keywords: Human CD8+ T cell; Human immune system mice; Malaria; Protection; Recombinant adenovirus