Varying immunizations with Plasmodium radiation-attenuated sporozoites alter tissue-specific CD8+ T cell dynamics

Frank R, Gabel M, Heiss K, Mueller AK, Graw F (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Frontiers in Immunology Frontiers Research Foundation / Frontiers Media

Book Volume: 9

Article Number: 1137

Journal Issue: MAY

DOI: 10.3389/fimmu.2018.01137

Abstract

Whole sporozoite vaccines 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. 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 toward 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.

Authors with CRIS profile

Frederik Graw

Involved external institutions

Universitätsklinikum Heidelberg DE Germany (DE) Ruprecht-Karls-Universität Heidelberg DE Germany (DE)

How to cite

APA:

Frank, R., Gabel, M., Heiss, K., Mueller, A.-K., & Graw, F. (2018). Varying immunizations with Plasmodium radiation-attenuated sporozoites alter tissue-specific CD8+ T cell dynamics. Frontiers in Immunology, 9(MAY). https://doi.org/10.3389/fimmu.2018.01137

MLA:

Frank, Roland, et al. "Varying immunizations with Plasmodium radiation-attenuated sporozoites alter tissue-specific CD8+ T cell dynamics." Frontiers in Immunology 9.MAY (2018).

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