Reliable estimation of the relationship between COVID-19 antibody levels at the time of exposure and the risk of infection is crucial to inform policy decisions on vaccination regimes. We fit a joint model of anti-spike IgG antibody decay and risk of COVID-19 infection to data from a randomized efficacy trial of the ChAdOx1 nCoV-19 vaccine. Our model improves upon previous analyses by accounting for measurement error, decay in antibody levels and variation between different individuals. We estimated correlates of protection, antibody decay, and vaccine efficacy waning. Increased anti-spike IgG antibody levels at the time of exposure correlate with increased vaccine-induced protection. We estimated vaccine efficacy against symptomatic COVID-19 infection of 88.1% (95% CrI: 77.2, 93.6) at day 35, waning to 60.4% (44.6, 71.0) at day 189 since the second dose. We report that longer intervals between the first and second vaccine dose give lasting increased protection, and observe lower efficacy in individuals aged ≥70 years from around 3 months after second dose. Our methods can be used in future vaccine trials to help inform the timings and priority of vaccine administration against novel diseases.

SF, AJP and MV are contributors to intellectual property licensed by Oxford University Innovation to AstraZeneca. AJP is Chair of the UK Department of Health and Social Care's (DHSC) Joint Committee on Vaccination & Immunisation (JCVI), but does not participate in discussions on COVID-19 vaccines. The authors report no other conflicts of interest.

NCT04400838

https://www.sciencedirect.com/science/article/pii/S0140673620326611?via%3Dihub

The collection of the data used in this work was supported by the UK Research and Innovation (MC PC 19055), Engineering and Physical Sciences Research Council (EP/R013756/1), National Institute for Health Research (COV19 OxfordVacc-01), Coalition for Epidemic Preparedness Innovations (Outbreak Response To Novel Coronavirus (COVID-19)), National Institute for Health Research Oxford Biomedical Research Centre (BRC4 Vaccines Theme), Chinese Academy of Medical Sciences Innovation Fund for Medical Science, China (2018-I2M-2- 002), Thames Valley and South Midlands NIHR Clinical Research Network. DJP discloses support for the research of this work from the Engineering and Physical Sciences Research Council (EP/W523781/1). The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care. AstraZeneca reviewed the final manuscript but the academic authors retained editorial control. Other funders had no role in study design, data collection and analysis, or decision to publish.

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