Modelling the World – can deliberately infecting healthy volunteers really tell us much about what happens outside the clinic during an epidemic or pandemic?

Abstract

With the emergence of the SARS-CoV-2 virus in 2019 and an ensuing pandemic that has swept the globe in record time, the need for rapid modelling of prophylactic vaccines and therapeutic drugs in disease intervention has never been greater. With some 120 drugs for COVID-19 currently in pre-clinical and clinical evaluation, moving step-wise through a series of traditionally structured tiers, the pace of evaluation is insufficient to provide immediate or even timely solutions to the crisis. The proven path of randomised, placebo-controlled clinical trials in community settings, where the ability to recruit suitably sized cohorts within populations subject to fluctuating disease incidences, is stretching the limited resources of clinics, pharma and governments and causing clinical trials to chase the breaking wave of transmission to achieve clinical relevance. The possibility of deliberately infecting consenting, healthy volunteers to directly measure drug and vaccine efficacy through viral and host markers may provide a fasttrack route to candidate selection, dose estimation, adjuvant class and routes of inoculation. The FDA and WHO have provided considered documents offering guidance and ethical reflections on the performance of such trials that have allowed for expert researchers in the field to look at developing wild-type SARS-CoV-2 challenge agents for use in appropriately structured studies and facilities with clear clinical oversight regarding safety as an a priori to protect the health and welfare of participants. Under this umbrella of ethical, clinical and scientific governance, a specialist human challenge CRO, hVIVO, has partnered with Imperial College and the Royal Free Hospital in London to characterise the world’s first SARS-CoV-2 challenge agent in preparation for COVID-19 vaccine efficacy trials. The UK Government has provided clearsighted and prescient leadership in adopting and funding this research tool as part of its pandemic response programme. With a global shortage of suitable isolation units (accredited to Biosafety Level 2+ or 3 as a minimum), the agreed requisition of infectious disease isolation wards has facilitated early works to commence whilst the world gears up to meet the need for the increased containment measures associated with emergence or pandemic diseases. Now more than ever, the success or failure of scientific and governmental organisations to provide effective solutions that protect the most vulnerable sections of the community is under scrutiny. With the immediacy of social media, vaccine-hesitancy in the face of poor efficacy or unwarranted side effects could cause rapid and irreparable damage to the perceived value of institutional intervention in infectious diseases, reducing the impact of not just this but other vaccination programmes to the detriment of populations world-wide.