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

PLoS One. 2018 Jan 12;13(1):e0190940. doi: 10.1371/journal.pone.0190940. eCollection 2018.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anopheles / parasitology
  • Antigens, Protozoan / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Immunologic Memory
  • Malaria Vaccines / immunology*
  • Mice
  • Mosquito Vectors
  • Plasmodium yoelii / immunology
  • Sporozoites / immunology*

Substances

  • Antigens, Protozoan
  • Malaria Vaccines