Journal article
Discriminating Protective from Nonprotective Plasmodium-Specific CD8+ T Cell Responses
The Journal of immunology (1950), Vol.196(10), pp.4253-4262
05/15/2016
DOI: 10.4049/jimmunol.1600155
PMCID: PMC4868661
PMID: 27084099
Abstract
Despite decades of research, malaria remains a global health crisis. Current subunit vaccine approaches do not provide efficient long-term, sterilizing immunity against Plasmodium infections in humans. Conversely, whole parasite vaccinations with their larger array of target Ags have conferred long-lasting sterilizing protection to humans. Similar studies in rodent models of malaria reveal that CD8(+) T cells play a critical role in liver-stage immunity after whole parasite vaccination. However, it is unknown whether all CD8(+) T cell specificities elicited by whole parasite vaccination contribute to protection, an issue of great relevance for enhanced subunit vaccination. In this article, we show that robust CD8(+) T cell responses of similar phenotype are mounted after prime-boost immunization against Plasmodium berghei glideosome-associated protein 5041-48-, sporozoite-specific protein 20318-325-, thrombospondin-related adhesion protein (TRAP) 130-138-, or circumsporozoite protein (CSP) 252-260-derived epitopes in mice, but only CSP252-260- and TRAP130-138-specific CD8(+) T cells provide sterilizing immunity and reduce liver parasite burden after sporozoite challenge. Further, CD8(+) T cells specific to sporozoite surface-expressed CSP and TRAP proteins, but not intracellular glideosome-associated protein 50 and sporozoite-specific protein 20, efficiently recognize sporozoite-infected hepatocytes in vitro. These results suggest that: 1) protection-relevant antigenic targets, regardless of their immunogenic potential, must be efficiently presented by infected hepatocytes for CD8(+) T cells to eliminate liver-stage Plasmodium infection; and 2) proteins expressed on the surface of sporozoites may be good target Ags for protective CD8(+) T cells.
Details
- Title: Subtitle
- Discriminating Protective from Nonprotective Plasmodium-Specific CD8+ T Cell Responses
- Creators
- Katherine L Doll - Department of Microbiology, University of Iowa, Iowa City, IA 52242Lecia L Pewe - Department of Microbiology, University of Iowa, Iowa City, IA 52242Samarchith P Kurup - Department of Microbiology, University of Iowa, Iowa City, IA 52242John T Harty - Department of Microbiology, University of Iowa, Iowa City, IA 52242; Department of Pathology, University of Iowa, Iowa City, IA 52242; and Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA 52242 john-harty@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.196(10), pp.4253-4262
- DOI
- 10.4049/jimmunol.1600155
- PMID
- 27084099
- PMCID
- PMC4868661
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- United States
- Grant note
- T32 AI007511 / NIAID NIH HHS R37 AI042747 / NIAID NIH HHS R37 AI042767 / NIAID NIH HHS R01 AI095178 / NIAID NIH HHS R01 AI085515 / NIAID NIH HHS R01 AI100527 / NIAID NIH HHS
- Language
- English
- Date published
- 05/15/2016
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984047750902771
Metrics
26 Record Views