Modeling the effect of boost timing in murine irradiated sporozoite prime-boost vaccines

作者：Cristina Fernández-Arias, Clemente Fernandez Arias, Min Zhang, Miguel A. Herrero, Francisco J. Acosta, Moriya Tsuji · 发表于：PLoS ONE · 年份：2018 · DOI：10.1371/journal.pone.0190940 · 被引用次数：12 · 研究领域：Immune Cell Function and Interaction、Malaria Research and Control、T-cell and B-cell Immunology

Vaccination with radiation-attenuated sporozoites has been shown to induce CD8+ T cell-mediated protection against pre-erythrocytic stages of malaria. Empirical evidence suggests that successive inoculations often improve the efficacy of this type of vaccines. An initial dose (prime) triggers a specific cellular response, and subsequent inoculations (boost) amplify this response to create a robust CD8+ T cell memory. In this work we propose a model to analyze the effect of T cell dynamics on the performance of prime-boost vaccines. This model suggests that boost doses and timings should be selected according to the T cell response elicited by priming. Specifically, boosting during late stages of clonal contraction would maximize T cell memory production for vaccines using lower doses of irradiated sporozoites. In contrast, single-dose inoculations would be indicated for higher vaccine doses. Experimental data have been obtained that support theoretical predictions of the model.