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

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.

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials

“…Greater protective efficacy associated with stronger immune responses after a wider prime-boost interval have been seen with other vaccines such as those for influenza, Ebola virus disease, and malaria. 16 , 17 , 18 The findings presented here for the ChAdOx1 nCoV-19 vaccine are consistent with policy recommendations in different countries to use dose intervals of 4–12 weeks for this vaccine.…”

Applicability of a Modified Rat Model of Acute Arthritis for Long-Term Testing of Drug Delivery Systems

“…Although most likely this is the case, the direction of the effect of this extension is unpredictable. Within a similar time frame, the effect of boost timing on the CD8+ T-cell memory response was shown to be dependent on the antigen itself, the antigen dose and actual exposure time [ 26 , 27 ], leading to enhancement of clonal expansion or to contraction [ 26 ]. This has not been investigated for this model and antigen.…”

Varying Immunizations With Plasmodium Radiation-Attenuated Sporozoites Alter Tissue-Specific CD8+ T Cell Dynamics

“…Identification of these antigen-dependent parameters is especially important to predict the influence of variations in the timing of immunizations on the generation of protective T cell responses. Using mathematical modeling, a previous study on the interaction of WSV dose and the timing of booster injections recently reported that boosting during the late phase of clonal contraction maximized memory T cell formation when using lower RAS doses, while a single inoculation was more effective in this respect when using a higher dose ( 54 ). However, this study only considered administration of a single boost not later than 7 days post priming and did not take into account the impact on interacting organ-specific or late memory responses.…”