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Using vaccine Immunostimulation/Immunodynamic modelling methods to inform vaccine dose decision-making.

ABSTRACT: Unlike drug dose optimisation, mathematical modelling has not been applied to vaccine dose finding. We applied a novel Immunostimulation/Immunodynamic mathematical modelling framework to translate multi-dose TB vaccine immune responses from mice, to predict most immunogenic dose in humans. Data were previously collected on IFN-? secreting CD4+ T cells over time for novel TB vaccines H56 and H1 adjuvanted with IC31 in mice (1 dose groups (0.1-1.5 and 15??g H56?+?IC31), 45 mice) and humans (1 dose (50??g H56/H1?+?IC31), 18 humans). A two-compartment mathematical model, describing the dynamics of the post-vaccination IFN-? T cell response, was fitted to mouse and human data, separately, using nonlinear mixed effects methods. We used these fitted models and a vaccine dose allometric scaling assumption, to predict the most immunogenic human dose. Based on the changes in model parameters by mouse H56?+?IC31 dose and by varying the H56 dose allometric scaling factor between mouse and humans, we established that, at a late time point (224 days) doses of 0.8-8??g H56?+?IC31 in humans may be the most immunogenic. A 0.8-8??g of H-series TB vaccines in humans, may be as, or more, immunogenic, as larger doses. The Immunostimulation/Immunodynamic mathematical modelling framework is a novel, and potentially revolutionary tool, to predict most immunogenic vaccine doses, and accelerate vaccine development.

SUBMITTER: Rhodes SJ

PROVIDER: S-EPMC6141590 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Using vaccine Immunostimulation/Immunodynamic modelling methods to inform vaccine dose decision-making.

Rhodes Sophie J SJ Guedj Jeremie J Fletcher Helen A HA Lindenstrøm Thomas T Scriba Thomas J TJ Evans Thomas G TG Knight Gwenan M GM White Richard G RG

NPJ vaccines 20180917

Unlike drug dose optimisation, mathematical modelling has not been applied to vaccine dose finding. We applied a novel Immunostimulation/Immunodynamic mathematical modelling framework to translate multi-dose TB vaccine immune responses from mice, to predict most immunogenic dose in humans. Data were previously collected on IFN-γ secreting CD4+ T cells over time for novel TB vaccines H56 and H1 adjuvanted with IC31 in mice (1 dose groups (0.1-1.5 and 15 μg H56 + IC31), 45 mice) and humans (1 dose ...[more]

PMID: 30245860

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Project description:BackgroundOrganised colorectal cancer screening is likely to be cost-effective, but cost-effectiveness results alone may not help policy makers to make decisions about programme feasibility or service providers to plan programme delivery. For these purposes, estimates of the impact on the health services of actually introducing screening in the target population would be helpful. However, these types of analyses are rarely reported. As an illustration of such an approach, we estimated annual health service resource requirements and health outcomes over the first decade of a population-based colorectal cancer screening programme in Ireland.MethodsA Markov state-transition model of colorectal neoplasia natural history was used. Three core screening scenarios were considered: (a) flexible sigmoidoscopy (FSIG) once at age 60, (b) biennial guaiac-based faecal occult blood tests (gFOBT) at 55-74 years, and (c) biennial faecal immunochemical tests (FIT) at 55-74 years. Three alternative FIT roll-out scenarios were also investigated relating to age-restricted screening (55-64 years) and staggered age-based roll-out across the 55-74 age group. Parameter estimates were derived from literature review, existing screening programmes, and expert opinion. Results were expressed in relation to the 2008 population (4.4 million people, of whom 700,800 were aged 55-74).ResultsFIT-based screening would deliver the greatest health benefits, averting 164 colorectal cancer cases and 272 deaths in year 10 of the programme. Capacity would be required for 11,095-14,820 diagnostic and surveillance colonoscopies annually, compared to 381-1,053 with FSIG-based, and 967-1,300 with gFOBT-based, screening. With FIT, in year 10, these colonoscopies would result in 62 hospital admissions for abdominal bleeding, 27 bowel perforations and one death. Resource requirements for pathology, diagnostic radiology, radiotherapy and colorectal resection were highest for FIT. Estimates depended on screening uptake. Alternative FIT roll-out scenarios had lower resource requirements.ConclusionsWhile FIT-based screening would quite quickly generate attractive health outcomes, it has heavy resource requirements. These could impact on the feasibility of a programme based on this screening modality. Staggered age-based roll-out would allow time to increase endoscopy capacity to meet programme requirements. Resource modelling of this type complements conventional cost-effectiveness analyses and can help inform policy making and service planning.

Project description:IntroductionThe vaccine distribution for the COVID-19 is a multicriteria decision-making (MCDM) problem based on three issues, namely, identification of different distribution criteria, importance criteria and data variation. Thus, the Pythagorean fuzzy decision by opinion score method (PFDOSM) for prioritising vaccine recipients is the correct approach because it utilises the most powerful MCDM ranking method. However, PFDOSM weighs the criteria values of each alternative implicitly, which is limited to explicitly weighting each criterion. In view of solving this theoretical issue, the fuzzy-weighted zero-inconsistency (FWZIC) can be used as a powerful weighting MCDM method to provide explicit weights for a criteria set with zero inconstancy. However, FWZIC is based on the triangular fuzzy number that is limited in solving the vagueness related to the aforementioned theoretical issues.ObjectivesThis research presents a novel homogeneous Pythagorean fuzzy framework for distributing the COVID-19 vaccine dose by integrating a new formulation of the PFWZIC and PFDOSM methods.MethodsThe methodology is divided into two phases. Firstly, an augmented dataset was generated that included 300 recipients based on five COVID-19 vaccine distribution criteria (i.e., vaccine recipient memberships, chronic disease conditions, age, geographic location severity and disabilities). Then, a decision matrix was constructed on the basis of an intersection of the 'recipients list' and 'COVID-19 distribution criteria'. Then, the MCDM methods were integrated. An extended PFWZIC was developed, followed by the development of PFDOSM.Results(1) PFWZIC effectively weighted the vaccine distribution criteria. (2) The PFDOSM-based group prioritisation was considered in the final distribution result. (3) The prioritisation ranks of the vaccine recipients were subject to a systematic ranking that is supported by high correlation results over nine scenarios of the changing criteria weights values.ConclusionThe findings of this study are expected to ensuring equitable protection against COVID-19 and thus help accelerate vaccine progress worldwide.

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Using vaccine Immunostimulation/Immunodynamic modelling methods to inform vaccine dose decision-making.

Publications

Using vaccine Immunostimulation/Immunodynamic modelling methods to inform vaccine dose decision-making.

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