State-of-art innovations in human in vitro 3D mucosa models and assays
In a nutshell
Subtopic 3 sets out to develop cell-based human in vitro 3D models that simulate an infection at the mucosa and more reliably predict immune protection. These models will be combined with the development of related functional immune assays for clinically relevant (surrogate) endpoints.
The scientific and technical objectives of this subtopic are:
Develop next-generation human in vitro 3D models for gastro-intestinal, respiratory and urovaginal mucosae that include relevant immune-system components
Test & validate the in vitro 3D models using selected Pathogens
Develop interventions and integrated functional immune assays addressing endpoints likely to be associated with protection and convalescence and evaluating novel immune surrogates of protection using existing samples and reagents and those from convalescent patients and other control subjects, human challenge models and vaccination studies
Use of pathogen strains representative of the expected heterogeneity encountered in patients
Academic leader: Cécile van Els, Rijksinstituut voor Volksgezondheid en Milieu (RIVM)
Industry co-leader: Fabienne Piras-Douce, Sanofi Pasteur
Project Manager: Kimberly Veenstra, EVI
Prof. Dr. Cécile van Els is Senior immunologist at RIVM and Professor of Vaccinology at the University of Utrecht, the Netherlands. She is an expert in the field of correlates of protection to human (respiratory) pathogens. Her current activities include identifying protective immune mechanisms and antigens in natural infection studies. Cécile has >100 publications.
Fabienne Piras-Douce is Senior Immunologist at Sanofi Pasteur, Marcy-l’Etoile, France. She is expert in pre-clinical and translational research for identifying relevant biomarkers of correlates of protection to support the selection of vaccine formulations. As research scientist in immunology, she has several publications on vaccine candidate evaluation such as Influenza, Cytomegalovirus, Yellow fever, Tuberculosis and Adjuvants.
Main WP objective
3D in vitro Models and assays: Roadmap, standardisation and guidelines
To accompany and underpin the scientific-technical development of the in vitro 3D mucosa models and assays by developing a strategy and roadmap for the ultimate integration of the models and assays into pharmaceutical vaccine development and to sustain project outputs long term.
Led by Katie Huber, Paul-Ehrlich-Institut (PEI) - the Federal Institute for Vaccines and Biomedicines and Shahjahan Shaid, GSK
Development of model and assay prototypes - Gastro-intestinal
Development of next generation in vitro 3D models of the gastrointestinal (GI) mucosa, based on human induced pluripotent stem cells (hiPSC) emulating essential organotypic microphysiological conditions created by precisely regulated biochemical and biophysical cues.
Led by Alexander Mosig, Jena University Hospital; Stephane Temmerman, GSK and Apurva Kulkarni, Takeda
Development of model and assay prototypes - Respiratory
Implement advanced next-generation respiratory mucosal models to evaluate vaccine-induced protective and detrimental immune responses in the context of infections with influenza and respiratory syncytial virus (RSV).
Led by Puck van Kasteren, Rijksinstituut voor Volksgezondheid en Milieu (RIVM); Nathalie Mantel, Sanofi and Kevin Buno, GSK
Development of model and assay prototypes - Urovaginal
Development of complex in vitro 3D infection models of the urovaginal (UV) mucosa with features resembling human tissue architecture and physiology and to explore the feasibility of including immune cells of innate and adaptive immune compartments to investigate protective effector immune mechanisms. We will focus on Neisseria gonorrhoeae (Ngo) and Herpes Simplex Virus-2 (HSV-2) to establish infection models.
Led by Thomas Rudel, Julius-Maximilians-Universität Würzburg (JMU) and Isabel Delany, GSK