Transfer of a non-human primate (NHP) in vitro functional assay for the early evaluation of TB vaccine candidates and the associated immune response

Tuberculosis (TB) remains a major global health threat, and the current vaccine (BCG) is inadequate. An improved vaccine is urgently needed, but in the absence of a validated alternative, candidate vaccines are currently tested in animal models such as mice, guinea pigs and non-human primates (NHPs). Animals are infected with pathogenic Mycobacterium tuberculosis (M.tb) following vaccination to determine efficacy; a procedure of Moderate Severity. As disease progresses, animals may experience loss of body weight, fever and respiratory distress and if left untreated will eventually die of pulmonary insufficiency; necessitating humane euthanasia. Dr Tanner has worked extensively on the development of an in vitro assay (the MGIT assay) as a correlate of protection, which may offer an alternative to in vivo M.tb infection and ultimately replace the use of animals in vaccine testing. NHPs are the most appropriate model to biologically validate the assay by comparing outcomes with measures of in vivo protection, allowing vaccine developers using this, and other preclinical models, to refine vaccine testing by replacing the infection stage. Rather, blood samples are taken from vaccinated animals and cells infected in vitro to measure vaccine efficacy. This project aims to transfer the NHP MGIT assay to two major end-user laboratories (Public Health England and the Biomedical Primate Research Centre) for use in their ongoing and future vaccine studies. Although preclinical testing may remain a regulatory requirement for progression to clinical trials, the early down-selection or gating of promising candidates using this assay will considerably reduce the numbers of animals challenged. In the longer-term, this work will offer the biological validation necessary to bridge to the use of human samples (as comparison with in vivo efficacy in humans is not logistically or ethically possible), which could largely replace the use of animals in TB vaccine efficacy testing.

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Skills and Knowledge Transfer grant

Status:

Not yet active

Principal investigator

Dr Rachel Tanner

Institution

University of Oxford

Co-Investigator

Dr Sally Sharpe
Dr Frank Verreck

Grant reference number

NC/R000905/1

Award date:

Jun 2017 - May 2018

Grant amount

£75,608