Dataset Information

Quality by design modelling to support rapid RNA vaccine production against emerging infectious diseases.

ABSTRACT: Rapid-response vaccine production platform technologies, including RNA vaccines, are being developed to combat viral epidemics and pandemics. A key enabler of rapid response is having quality-oriented disease-agnostic manufacturing protocols ready ahead of outbreaks. We are the first to apply the Quality by Design (QbD) framework to enhance rapid-response RNA vaccine manufacturing against known and future viral pathogens. This QbD framework aims to support the development and consistent production of safe and efficacious RNA vaccines, integrating a novel qualitative methodology and a quantitative bioprocess model. The qualitative methodology identifies and assesses the direction, magnitude and shape of the impact of critical process parameters (CPPs) on critical quality attributes (CQAs). The mechanistic bioprocess model quantifies and maps the effect of four CPPs on the CQA of effective yield of RNA drug substance. Consequently, the first design space of an RNA vaccine synthesis bioreactor is obtained. The cost-yield optimization together with the probabilistic design space contribute towards automation of rapid-response, high-quality RNA vaccine production.

SUBMITTER: van de Berg D

PROVIDER: S-EPMC8085199 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Quality by design modelling to support rapid RNA vaccine production against emerging infectious diseases.

van de Berg Damien D Kis Zoltán Z Behmer Carl Fredrik CF Samnuan Karnyart K Blakney Anna K AK Kontoravdi Cleo C Shattock Robin R Shah Nilay N

NPJ vaccines 20210429 1

Rapid-response vaccine production platform technologies, including RNA vaccines, are being developed to combat viral epidemics and pandemics. A key enabler of rapid response is having quality-oriented disease-agnostic manufacturing protocols ready ahead of outbreaks. We are the first to apply the Quality by Design (QbD) framework to enhance rapid-response RNA vaccine manufacturing against known and future viral pathogens. This QbD framework aims to support the development and consistent producti ...[more]

PMID: 33927197

Similar Datasets

Project description:Vaccine allocation strategies become crucial during vaccine shortages, especially in the face of potential outbreaks of new infectious diseases, as witnessed during the COVID-19 pandemic. To address this, a specialized compartmental model is created, which simulates an emerging infectious disease similar to COVID-19. This model divides the population into different age groups and is used to compare various vaccine prioritisation approaches, aiming to minimize the total number of fatalities. The model is an improvement upon previous ones as it incorporates essential behavioural factors and is adapted to account for the protective effects of vaccination against both disease infection and transmission. It takes into account human behaviors such as mask-wearing and social distancing by utilizing specific parameters related to self-protection, awareness levels, and the frequency of daily person-to-person interactions within each age group. Furthermore, a novel method for dynamic vaccine prioritisation was introduced in this study. This approach is model-independent and relies on the dynamic R number. It is the first time such a method has been developed, offering a decision-making approach that is not tied to any specific model. This innovation provides a flexible and adaptable strategy for determining vaccine priorities based on real-time data and the current state of the outbreak. Our findings reveal crucial insights into vaccine allocation strategies. When the daily rollout rates are fast (0.75% or higher) and children are eligible for vaccination, prioritising groups with high daily person-to-person interactions can lead to substantial reductions in total fatalities (up to approximately 40% lower). On the other hand, if rollout rates are slower and overall vaccination coverage is high, focusing on vaccinating elders emerges as the most effective strategy, resulting in up to approximately 10% fewer fatalities. However, the scenario changes significantly when children are not eligible for vaccination, as they constitute a highly interactive population group. In this case, the differences between priority strategies become smaller. With fast daily rollout rates, prioritisation based on interactions achieves only a 7% reduction in total fatalities, while a slower rollout with vaccination of elders first leads to an approximately 11% reduction in fatalities compared to the scenario where children are eligible for vaccination. The impact of behavioural parameters is equally critical. When the self-protection levels exercised by the population are low, it significantly affects the optimal vaccine prioritisation strategy to be followed, making it essential to consider behavioural factors in decision-making.

Project description:Emerging infectious diseases (EIDs) caused by viruses are increasing in frequency, causing a high disease burden and mortality world-wide. The COVID-19 pandemic caused by the novel SARS-like coronavirus (SARS-CoV-2) underscores the need to innovate and accelerate the development of effective vaccination strategies against EIDs. Human leukocyte antigen (HLA) molecules play a central role in the immune system by determining the peptide repertoire displayed to the T-cell compartment. Genetic polymorphisms of the HLA system thus confer a strong variability in vaccine-induced immune responses and may complicate the selection of vaccine candidates, because the distribution and frequencies of HLA alleles are highly variable among different ethnic groups. Herein, we build on the emerging paradigm of rational epitope-based vaccine design, by describing an immunoinformatics tool (Predivac-3.0) for proteome-wide T-cell epitope discovery that accounts for ethnic-level variations in immune responsiveness. Predivac-3.0 implements both CD8+ and CD4+ T-cell epitope predictions based on HLA allele frequencies retrieved from the Allele Frequency Net Database. The tool was thoroughly assessed, proving comparable performances (AUC ~0.9) against four state-of-the-art pan-specific immunoinformatics methods capable of population-level analysis (NetMHCPan-4.0, Pickpocket, PSSMHCPan and SMM), as well as a strong accuracy on proteome-wide T-cell epitope predictions for HIV-specific immune responses in the Japanese population. The utility of the method was investigated for the COVID-19 pandemic, by performing in silico T-cell epitope mapping of the SARS-CoV-2 spike glycoprotein according to the ethnic context of the countries where the ChAdOx1 vaccine is currently initiating phase III clinical trials. Potentially immunodominant CD8+ and CD4+ T-cell epitopes and population coverages were predicted for each population (the Epitope Discovery mode), along with optimized sets of broadly recognized (promiscuous) T-cell epitopes maximizing coverage in the target populations (the Epitope Optimization mode). Population-specific epitope-rich regions (T-cell epitope clusters) were further predicted in protein antigens based on combined criteria of epitope density and population coverage. Overall, we conclude that Predivac-3.0 holds potential to contribute in the understanding of ethnic-level variations of vaccine-induced immune responsiveness and to guide the development of epitope-based next-generation vaccines against emerging pathogens, whose geographic distributions and populations in need of vaccinations are often well-defined for regional epidemics.

Dataset Information

Quality by design modelling to support rapid RNA vaccine production against emerging infectious diseases.

Publications

Quality by design modelling to support rapid RNA vaccine production against emerging infectious diseases.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets