Human CD8+ T cells mediate protective immunity induced by a human malaria vaccine in human immune system mice. Issue 38 (31st August 2016)

• Record Type: Journal Article
• Authors: Li, Xiangming; Huang, Jing; Zhang, Min; Funakoshi, Ryota; Sheetij, Dutta; Spaccapelo, Roberta; Crisanti, Andrea; Nussenzweig, Victor; Nussenzweig, Ruth S.; Tsuji, Moriya
• Is Part Of: Vaccine. Volume 34:Issue 38(2016)
• Page Start: 4501
• Page End: 4506
• Publication Date: 2016-08-31
• Subjects: Ad adenovirus -- AAV9 adeno-associated virus serotype 9 -- CSP circumsporozoite protein -- FL full-length -- HIS human immune system -- Pf Plasmodium falciparum -- Py Plasmodium yoelii -- TCR T-cell receptor; Human CD8+ T cell -- Human immune system mice -- Protection -- Malaria -- Recombinant adenovirus; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2016.08.006
• Languages: English
• ISSNs: 0264-410X

Abstract

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 .