CHIMICHURRI
ST2
Controlled Human Infection Models (CHIMs)
In a nutshell
Subtopic 2 is dedicated to the development of new and improved controlled human infection models (CHIM) for influenza (i.e., flu), Respiratory Syncytial Virus (RSV, i.e., a common respiratory virus that can be serious for infants and older adults) and Clostridium difficile (i.e., a bacterium that can infect the intestine and cause diarrhoea) that will enable early vaccine efficacy evaluation.
What is a Controlled Human Infection Model (CHIM)?
An established model which purposefully infects humans with an infectious agent in a controlled situation to achieve relevant and generalizable endpoints of infection or disease and a reproducible attack rate. The model meets all safety and ethical standards and has received regulatory approval. It uses a well-studied (GMP-produced and stored) inoculum, dose, and route.
(Source: 2018 Global Vaccine and Immunization Research Forum March 20, 2018 Beth Kirkpatrick, MD).
The scientific and technical objectives of this subtopic are:
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Develop a strategy, including ethical and environmental considerations for the integration of CHIMs into pharmaceutical development. Optimized pipelines for identification, characterization & GMP manufacture of new challenge pathogen strains
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Clinically evaluate the challenge agents
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Develop novel CHIMs to enable investigation of protective immunity in the lung and with older age population
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Position newly developed CHIMs in the regulatory framework by addressing hurdles to regulatory acceptance
Academic leader: Meta Roestenberg, Leiden University Medical Center
Industry co-leader: Jeanne Marie Devaster, GSK
Project Manager: Nicoletta Corti, EVI
Meta and her team have >15 years of experience in the development of controlled human infection models to test novel vaccines and drugs, bringing together clinical as well as fundamental scientists to maximize the scientific output of such clinical trials.
Jeanne Marie Devaster, MD, is a clinical Microbiologist at GSK and will act as industry lead. She has 21 years of experience in Clinical development of vaccines and is currently the clinical and Epidemiology Lead of the Early Discovery Vaccine Projects in GSK, Belgium
Workpackages
Main WP objective
WP6
Roadmap for CHIM development and standardization, considering
ethical & environmental issues (Influenza, RSV, C. difficile)
Led by Nicoletta Corti, European Vaccine Initiative
Develop a strategy and roadmap for the integration of CHIM into pharmaceutical vaccine development.
WP7
Clinical study coordination (Influenza, RSV, C. difficile)
Led by Meta Roestenberg, Leiden University Medical Center
Coordinate (prepare and manage) clinical trial activities, supporting WP8, WP9 and WP10 tasks and deliverables
WP8
Identification, manufacture and clinical evaluation of challenge strains (Influenza)
Led by Rebecca Cox, University of Bergen
Establish a standardized CHIM for influenza available to investigators across Europe through selection and creation of a challenge strain relevant to “universal” influenza vaccine development; improved standardization through harmonization of clinical and laboratory methods; and understanding of the role of immune correlates of protection, both with regards to pre-existing immunity and with a focus on the respiratory tract.
WP9
Identification, manufacture and clinical evaluation of challenge strains (RSV)
Led by Chris Chiu, Imperial College London
Develop a novel CHIM using an RSV B strain that addresses a gap in the field and use this to establish a consensus approach to conducting optimally-informative RSV CHIM trials across Europe.
WP10
Identification, manufacture and clinical evaluation of challenge strains (C. difficile)
Led by Wiep Smits, Leiden University Medical Center
Develop and test a CHIM model for toxigenic C. difficile infection (CDI) as a standardized resource for future CDI vaccine testing.
WP11
Positioning newly developed CHIMs in regulatory framework (potential & limitations)
Led by Pieter Neels, International Alliance for Biological Standardization
Provide support to the CHIM developers, on where to seek regulatory advice and which aspects may be critical for regulatory acceptance. The WP will further involve research aspects related to safety of CHIM and HCT, quality aspects of challenge agent manufacturing as well as to clarifying the legal framework around CHIM.