Modeling the effect of boost timing in murine irradiated sporozoite prime-boost vaccines.
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Abstract | :
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. |
Year of Publication | :
0
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Journal | :
PloS one
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Volume | :
13
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Issue | :
1
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Number of Pages | :
e0190940
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Date Published | :
2018
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DOI | :
10.1371/journal.pone.0190940
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Short Title | :
PLoS One
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