Immunologic Memory: T Cells in Humans

Iglesias, María Candela; Appay, Victor; Moris, Arnaud

doi:10.1002/9781118345313.ch5

Cited by 2 publications

(10 citation statements)

References 106 publications

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“…Also in line with empirical observations, the model predicts that the extent of such changes is determined by the magnitude of the clonal expansion of T cells that respond to the pathogen ( Fig 2C ) [ 54 , 55 ]. In turn, the peak of clonal expansion is known to be related to the affinity of effector T cells for their cognate antigens [ 20 , 31 , 56 ], and can be modulated by the presence of inflammatory cytokines [ 57 ]. As noted above, these situations can be modeled by assigning higher values to parameter λ AP in Eq (1) (see Fig 2D ).…”

Section: Resultsmentioning

confidence: 99%

“…Accordingly, we suggest that this model can provide valuable insight to be applied in the design of PB vaccines against malaria. In particular, we will show that it can be used to analyze the effect of boost timing on the formation of memory T cells, a variable that has been observed to correlate with vaccine-induced protection [ 20 , 62 , 63 ].…”

Section: Resultsmentioning

confidence: 99%

“…Empirical evidence suggests that prime-boost (PB) regimes can improve the efficacy of this type of vaccines, as compared to single-dose strategies [ 11 , 20 , 21 ]. In PB vaccines, an initial inoculation (prime) serves to generate a population of antigen-specific effector T cells, and subsequent inoculations of the same or a different vector (boost) promote expansion of this population, thus increasing the pool of long-lasting specific immune memory [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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“…The protection induced by vaccines against certain pathogens requires the generation of effective cell-mediated immunity [1][2][3]. In particular, a great research effort is currently focused on the development of vaccines aimed at eliciting strong response in T cells (a key component of our immune system).…”

Section: Introductionmentioning

confidence: 99%

“…In particular, a great research effort is currently focused on the development of vaccines aimed at eliciting strong response in T cells (a key component of our immune system). A number of studies have shown that the efficiency of T cell-based vaccines can be greatly improved by using prime-boost (PB) regimes [1,4]. The rationale of PB vaccines is to use an initial inoculation (prime) to activate specific clones of T cells.…”

Section: Introductionmentioning

confidence: 99%

Modeling the Dependence of Immunodominance on T Cell Dynamics in Prime-Boost Vaccines

et al. 2020

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The protection induced by vaccines against infectious diseases such as malaria, dengue or hepatitis relies on a the creation of immune memory by T cells, key components of the human immune system. The induction of a strong T cell response leading to long lasting memory can be improved by using prime-boost (PB) vaccines, which consist in successive inoculations of appropriate vectors carrying target antigens that can be recognized by specific T cell clones. A problem faced by PB vaccines is the fact that T cell response is often biased towards a few clones that can identify only a small set of antigens, out of the many that could be displayed by the pathogen. This phenomenon, known as immunodominance, can significantly compromise the effectiveness of vaccination. In this work we will use mathematical modeling to better understand the role of T cell population dynamics in the onset of immunodominance in PB vaccines. In particular, we will use mathematical analysis and simulations to compare single-dose vaccines with PB ones, both for homologous (where the same antigen is used in every shot) and heterologous protocols (in which different antigens are used at each step).

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Immunologic Memory: T Cells in Humans

Cited by 2 publications

References 106 publications

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

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

Modeling the Dependence of Immunodominance on T Cell Dynamics in Prime-Boost Vaccines

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