A quantitative systems pharmacology approach to support mRNA vaccine development and optimization

Selvaggio, Gianluca; Leonardelli, Lorena; Lofano, Giuseppe; Fresnay, Stephanie; Parolo, Silivia; Medini, Duccio; Siena, Emilio; Marchetti, Luca

doi:10.1002/psp4.12721

Cited by 12 publications

(7 citation statements)

References 11 publications

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“…The current model approach can be positioned between a very complex approach, as the quantitative system pharmacology (QSP) models, 37 , 38 , 39 , 40 , 41 and a simpler one, as the empirical models (i.e., power law or exponential models) 42 widely used in vaccine development. The mechanistic modeling approach presented in the current work has four advantages: (1) it constitutes a step forward with respect to predictability compared to the empirical models, (2) is less complex than a QSP model but accounts for the key elements of the immune response, (3) is informed by the available clinical data, and finally, (4) uses the nonlinear mixed effect modeling methodology, which not only allows to describe the biological system of interest and its intersubject variability, but also enables to evaluate the effect of different covariates on the estimated parameter outcomes.…”

Section: Discussionmentioning

confidence: 99%

Mechanistic modeling projections of antibody persistence after homologous booster regimens of COVID‐19 vaccine Ad26.COV2.S in humans

Dari,

Jacqmin,

Iwaki

et al. 2023

CPT Pharmacom & Syst Pharma

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Mechanistic model‐based simulations can be deployed to project the persistence of humoral immune response following vaccination. We used this approach to project the antibody persistence through 24 months from the data pooled across five clinical trials in severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2)‐seronegative participants following vaccination with Ad26.COV2.S (5 × 1010 viral particles), given either as a single‐dose or a homologous booster regimen at an interval of 2, 3, or 6 months. Antibody persistence was quantified as the percentage of participants with detectable anti‐spike binding and wild‐type virus neutralizing antibodies. The projected overall 24‐month persistence after single‐dose Ad26.COV2.S was 70.5% for binding antibodies and 55.2% for neutralizing antibodies, and increased after any homologous booster regimen to greater than or equal to 89.9% for binding and greater than or equal to 80.0% for neutralizing antibodies. The estimated model parameters quantifying the rates of antibody production attributed to short‐lived and long‐lived plasma cells decreased with increasing age, whereas the rate of antibody production mediated by long‐lived plasma cells was higher in women relative to men. Accordingly, a more pronounced waning of antibody responses was predicted in men aged greater than or equal to 60 years and was markedly attenuated following any homologous boosting regimen. The findings suggest that homologous boosting might be a viable strategy for maintaining protective effects of Ad26.COV2.S for up to 24 months following prime vaccination. The estimation of mechanistic modeling parameters identified the long‐lived plasma cell pathway as a key contributor mediating antibody persistence following single‐dose and homologous booster vaccination with Ad26.COV2.S in different subgroups of recipients stratified by age and sex.

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Section: Discussionmentioning

confidence: 99%

Mechanistic modeling projections of antibody persistence after homologous booster regimens of COVID‐19 vaccine Ad26.COV2.S in humans

Dari,

Jacqmin,

Iwaki

et al. 2023

CPT Pharmacom & Syst Pharma

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“…Besides these engineering options, better purified preparations without EDTA and human proteins, which are inflammatory and a major cause of side effects with the ChAdox1 vaccines [ 55 ], should be made mandatory for clinical use. Moreover, the vaccine administration dose may be optimized with the help of computer models [ 86 ] or dose fractionation, which consists of using a lower dose for the prime than for the boost and was associated with higher quality of the immune response [ 87 ]. Besides these factors, the administration route may be imporant.…”

Section: Strategies To Improve the Adenovirus Vector Platformmentioning

confidence: 99%

The Adenovirus Vector Platform: Novel Insights into Rational Vector Design and Lessons Learned from the COVID-19 Vaccine

Sallard

Zhang

Aydin

et al. 2023

Viruses

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The adenovirus vector platform remains one of the most efficient toolboxes for generation of transfer vehicles used in gene therapy and virotherapy to treat tumors, as well as vaccines to protect from infectious diseases. The adenovirus genome and capsids can be modified using highly efficient techniques, and vectors can be produced at high titers, which facilitates their rapid adaptation to current needs and disease applications. Over recent years, the adenovirus vector platform has been in the center of attention for vaccine development against the ongoing coronavirus SARS-CoV-2/COVID-19 pandemic. The worldwide deployment of these vaccines has greatly deepened the knowledge on virus-host interactions and highlighted the need to further improve the effectiveness and safety not only of adenovirus-based vaccines but also of gene therapy and oncolytic virotherapy vectors. Based on the current evidence, we discuss here how adenoviral vectors can be further improved by intelligent molecular design. This review covers the full spectrum of state-of-the-art strategies to avoid vector-induced side effects ranging from the vectorization of non-canonical adenovirus types to novel genome engineering techniques.

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“…many more doses than would otherwise be feasible, even in the largest of clinical studies. "You can test a wider range of scenarios in silico," says Luca Marchetti, a computer scientist at the Microsoft Research-University of Trento Centre for Computational and Systems Biology in Rovereto, Italy, who last year developed a model to support mRNA-vaccine development 9 .…”

Section: Model Makersmentioning

confidence: 99%

Could computer models be the key to better COVID vaccines?

Dolgin¹

2022

Nature

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A quantitative systems pharmacology approach to support mRNA vaccine development and optimization

Cited by 12 publications

References 11 publications

Mechanistic modeling projections of antibody persistence after homologous booster regimens of COVID‐19 vaccine Ad26.COV2.S in humans

Mechanistic modeling projections of antibody persistence after homologous booster regimens of COVID‐19 vaccine Ad26.COV2.S in humans

The Adenovirus Vector Platform: Novel Insights into Rational Vector Design and Lessons Learned from the COVID-19 Vaccine

Could computer models be the key to better COVID vaccines?

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