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Journal article : Review

Controlled human infection models in COVID-19 and tuberculosis: current progress and future challenges

Abstract:

Controlled Human Infection Models (CHIMs) involve deliberately exposing healthy human volunteers to a known pathogen, to allow the detailed study of disease processes and evaluate methods of treatment and prevention, including next generation vaccines. CHIMs are in development for both tuberculosis (TB) and Covid-19, but challenges remain in their ongoing optimisation and refinement. It would be unethical to deliberately infect humans with virulent Mycobacteria tuberculosis (M.tb), however surrogate models involving other mycobacteria, M.tb Purified Protein Derivative or genetically modified forms of M.tb either exist or are under development. These utilise varying routes of administration, including via aerosol, per bronchoscope or intradermal injection, each with their own advantages and disadvantages. Intranasal CHIMs with SARS-CoV-2 were developed against the backdrop of the evolving Covid-19 pandemic and are currently being utilised to both assess viral kinetics, interrogate the local and systemic immunological responses post exposure, and identify immune correlates of protection. In future it is hoped they can be used to assess new treatments and vaccines. The changing face of the pandemic, including the emergence of new virus variants and increasing levels of vaccination and natural immunity within populations, has provided a unique and complex environment within which to develop a SARS-CoV-2 CHIM. This article will discuss current progress and potential future developments in CHIMs for these two globally significant pathogens.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.3389/fimmu.2023.1211388

Authors


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Role:
Author
ORCID:
0000-0003-0152-3033
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Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Jenner Institute
Role:
Author
ORCID:
0000-0002-2126-5142



Publisher:
Frontiers Media
Journal:
Frontiers in Immunology More from this journal
Volume:
14
Article number:
1211388
Publication date:
2023-05-25
Acceptance date:
2023-05-09
DOI:
EISSN:
1664-3224
Pmid:
37304270


Language:
English
Keywords:
Subtype:
Review
Pubs id:
1461701
Local pid:
pubs:1461701
Deposit date:
2023-06-29

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