The TB vaccine H56+IC31 dose-response curve is peaked not saturating: Data generation for new mathematical modelling methods to inform vaccine dose decisions

Rhodes, Sophie; Zelmer, Andrea; Knight, Gwenan M.; Prabowo, Satria A.; Stockdale, Lisa; Evans, Thomas G.; Lindenstrøm, Thomas; White, Richard G.; Fletcher, Helen A.

doi:10.1016/j.vaccine.2016.10.060

Cited by 21 publications

(32 citation statements)

References 22 publications

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“…IS/ID modelling was applied to determine the dose-response curve and showed a definitive n-shape for multiple times points after vaccination [11]. This strongly suggests that the predicted best dose is likely to be lower than previously investigated [11]. Preliminary work has also been conducted to simulate further responses (based on these empirical data) to obtain optimal dosing cohorts and narrow the confidence interval around predicted best dose.…”

Section: Current Is/id Modellingmentioning

confidence: 99%

Dose finding for new vaccines: The role for immunostimulation/immunodynamic modelling

Rhodes

Knight

Kirschner

et al. 2019

Journal of Theoretical Biology

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Current methods to optimize vaccine dose are purely empirically based, whereas in the drug development field, dosing determinations use far more advanced quantitative methodology to accelerate decision-making. Applying these established methods in the field of vaccine development may reduce the currently large clinical trial sample sizes, long time frames, high costs, and ultimately have a better potential to save lives. We propose the field of immunostimulation/immunodynamic (IS/ID) modelling, which aims to translate mathematical frameworks used for drug dosing towards optimizing vaccine dose decisionmaking. Analogous to PK/PD modelling, IS/ID modelling approaches apply mathematical models to describe the underlying mechanisms by which the immune response is stimulated by vaccination (IS) and the resulting measured immune response dynamics (ID). To move IS/ID modelling forward, existing datasets and further data on vaccine allometry and dosedependent dynamics need to be generated and collate, requiring a collaborative environment with input from academia, industry, regulators, governmental and non-governmental agencies to share modelling expertise, and connect modellers to vaccine data.

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Section: Current Is/id Modellingmentioning

confidence: 99%

Dose finding for new vaccines: The role for immunostimulation/immunodynamic modelling

Rhodes

Knight

Kirschner

et al. 2019

Journal of Theoretical Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently developed mathematical modelling methods, referred to as immunostimulation/immunodynamic (IS/ID) modelling, attempts to address these issues [7][8][9][10]. IS/ID modelling was developed to address the lack of quantitative methods in vaccine development [11].…”

Section: Introductionmentioning

confidence: 99%

“…The aim of IS/ID is to translate pharmacokinetic/pharmacodynamic (PK/PD) methodology to vaccine development, and preliminary IS/ID modelling has shown promise in accelerating vaccine dosing decisions. Modelling of the dose-response curve and cross-species translation of tuberculosis vaccine dosing data have predicted a lower human dose than previously tested [7,9], and showed that antibody response against human parainfluenza virus may be maximised by an intermediate dose [12]. To inform future IS/ID modelling, dose-response data must be collated.…”

Section: Introductionmentioning

confidence: 99%

Immunologic Dose-Response to Adenovirus-Vectored Vaccines in Animals and Humans: A Systematic Review of Dose-Response Studies of Replication Incompetent Adenoviral Vaccine Vectors when Given via an Intramuscular or Subcutaneous Route

et al. 2020

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Optimal vaccine dosing is important to ensure the greatest protection and safety. Analysis of dose-response data, from previous studies, may inform future studies to determine the optimal dose. Implementing more quantitative modelling approaches in vaccine dose finding have been recently suggested to accelerate vaccine development. Adenoviral vectored vaccines are in advanced stage of development for a variety of prophylactic and therapeutic indications, however dose-response has not yet been systematically determined. To further inform adenoviral vectored vaccines dose identification, historical dose-response data should be systematically reviewed. A systematic literature review was conducted to collate and describe the available dose-response studies for adenovirus vectored vaccines. Of 2787 papers identified by Medline search strategy, 35 were found to conform to pre-defined criteria. The majority of studies were in mice or humans and studied adenovirus serotype 5. Dose-response data were available for 12 different immunological responses. The majority of papers evaluated three dose levels, only two evaluated more than five dose levels. The most common dosing range was 107–1010 viral particles in mouse studies and 108–1011 viral particles in human studies. Data were available on adenovirus vaccine dose-response, primarily on adenovirus serotype 5 backbones and in mice and humans. These data could be used for quantitative adenoviral vectored vaccine dose optimisation analysis.

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“…A peaking relationship implies that there exists some dose for which the response is maximised, and that an increase in dose would lead to a decreased response. Historically, pre-clinical trials typically have made the assumption of a saturating curve shape [6]; however, research has shown that for both tuberculosis and influenza vaccines a peaking shape may better describe the dose-response curve [7,8]. Adenoviral vaccine dose-response curve shape has not yet been established.…”

Section: Introductionmentioning

confidence: 99%

Response Type and Host Species may be Sufficient to Predict Dose-Response Curve Shape for Adenoviral Vector Vaccines

et al. 2020

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Vaccine dose-response curves can follow both saturating and peaking shapes. Dose-response curves for adenoviral vector vaccines have not been systematically described. In this paper, we explore the dose-response shape of published adenoviral animal and human studies. Where data were informative, dose-response was approximately five times more likely to be peaking than saturating. There was evidence that host species and response type may be sufficient for prediction of dose-response curve shape. Dose-response curve shape prediction could decrease clinical trial costs, accelerating the development of life-saving vaccines.

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The TB vaccine H56+IC31 dose-response curve is peaked not saturating: Data generation for new mathematical modelling methods to inform vaccine dose decisions

Cited by 21 publications

References 22 publications

Dose finding for new vaccines: The role for immunostimulation/immunodynamic modelling

Dose finding for new vaccines: The role for immunostimulation/immunodynamic modelling

Immunologic Dose-Response to Adenovirus-Vectored Vaccines in Animals and Humans: A Systematic Review of Dose-Response Studies of Replication Incompetent Adenoviral Vaccine Vectors when Given via an Intramuscular or Subcutaneous Route

Response Type and Host Species may be Sufficient to Predict Dose-Response Curve Shape for Adenoviral Vector Vaccines

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