Testing SARS-CoV-2 vaccine efficacy through deliberate natural viral exposure

Abstract

\n Background\n A vaccine trial with a conventional challenge design can be very fast once it starts, but it requires a long prior process, in part, to grow and standardize challenge virus in the laboratory. This detracts somewhat from its overall promise for accelerated efficacy testing of SARS-CoV-2 vaccine candidates, and from the ability of developing countries and small companies to conduct it.\n \n Objectives\n We set out to identify a challenge design that avoids this part of the long prior process.\n \n Sources\n Literature in trial design (including a proof of concept flu challenge trial by B. Killingley et al), vaccinology, medical ethics, and various aspects of COVID response.\n \n Content\n A challenge design with deliberate natural viral exposure avoids the need to grow culture. This new design is described and compared both to a conventional challenge design and to a conventional phase III field trial. In comparison, the propsed design has ethical, scientific, and feasibility strengths.\n \n Implications\n The proposed new design should be considered for future vaccine trials.\n