Varying immunizations with plasmodium radiation-attenuated sporozoites alter tissue-specific CD8+ T cell dynamics
Whole sporozoite vaccines (WSV) represent one of the most promising strategies to induce protection against malaria. However, the development of efficient vaccination protocols still remains a major challenge. To understand how the generation of immunity is affected by variations in vaccination dosa...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
28 May 2018
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| In: |
Frontiers in immunology
Year: 2018, Volume: 9 |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2018.01137 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.3389/fimmu.2018.01137 Verlag, kostenfrei, Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2018.01137/full 
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| Author Notes: | Roland Frank, Michael Gabel, Kirsten Heiss, Ann-Kristin Mueller and Frederik Graw |
| Summary: | Whole sporozoite vaccines (WSV) represent one of the most promising strategies to induce protection against malaria. However, the development of efficient vaccination protocols still remains a major challenge. To understand how the generation of immunity is affected by variations in vaccination dosage and frequency, we systematically analyzed intrasplenic and intrahepatic CD8+ T cell responses following varied immunizations of mice with radiation-attenuated sporozoites (RAS). By combining experimental data and mathematical modeling, our analysis indicates a reversing role of spleen and liver in the generation of protective liver-resident CD8+ T cells during priming and booster injections: While the spleen acts as a critical source compartment during priming, the increase in vaccine-induced hepatic T cell levels is likely due to local reactivation in the liver in response to subsequent booster injections. Higher dosing accelerates the efficient generation of liver-resident CD8+ T cells by especially affecting their local reactivation. In addition, we determine the differentiation and migration pathway from splenic precursors towards hepatic memory cells thereby presenting a mechanistic framework for the impact of various vaccination protocols on these dynamics. Thus, our work provides important insights into organ-specific CD8+ T cell dynamics and their role and interplay in the formation of protective immunity against malaria. |
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| Item Description: | Das Pluszeichen ist im Titel hochgestellt Gesehen am 24.07.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2018.01137 |