Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection

the Oxford COVID Vaccine Trial Group

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Defined levels of SARS-CoV-2-specific binding and neutralizing antibodies elicited by the COVID-19 vaccine ChAdOx1 nCoV-19 are identified as correlates of protection against symptomatic infection.

The global supply of COVID-19 vaccines remains limited. An understanding of the immune response that is predictive of protection could facilitate rapid licensure of new vaccines. Data from a randomized efficacy trial of the ChAdOx1 nCoV-19 (AZD1222) vaccine in the United Kingdom was analyzed to determine the antibody levels associated with protection against SARS-CoV-2. Binding and neutralizing antibodies at 28 days after the second dose were measured in infected and noninfected vaccine recipients. Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. A vaccine efficacy of 80% against symptomatic infection with majority Alpha (B.1.1.7) variant of SARS-CoV-2 was achieved with 264 (95% CI: 108, 806) binding antibody units (BAU)/ml: and 506 (95% CI: 135, not computed (beyond data range) (NC)) BAU/ml for anti-spike and anti-RBD antibodies, and 26 (95% CI: NC, NC) international unit (IU)/ml and 247 (95% CI: 101, NC) normalized neutralization titers (NF50) for pseudovirus and live-virus neutralization, respectively. Immune markers were not correlated with asymptomatic infections at the 5% significance level. These data can be used to bridge to new populations using validated assays, and allow extrapolation of efficacy estimates to new COVID-19 vaccines.

Original languageEnglish
Number of pages28
JournalNature Medicine
Early online date29 Sep 2021
DOIs
Publication statusE-pub ahead of print - 29 Sep 2021

Bibliographical note

Funding Information:
This article reports independent research funded by UK Research and Innovation (MC_PC_19055: SG, AJP, TL), Engineering and Physical Sciences Research Council (EP/R013756/1: S.C.G., A.J.P., T.L.), National Institute for Health Research (COV19 OxfordVacc-01: S.C.G., A.J.P., T.L.), Coalition for Epidemic Preparedness Innovations (Outbreak Response To Novel Coronavirus (COVID-19: S.C.G., A.J.P., T.L.)), National Institute for Health Research Oxford Biomedical Research Centre (BRC4 Vaccines Theme), Thames Valley and South Midland’s NIHR Clinical Research Network, and AstraZeneca. 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. We acknowledge support from Thames Valley and South Midland’s NIHR Clinical Research Network and the staff and resources of NIHR Southampton Clinical Research Facility and the NIHR Oxford Biomedical Research Centre. A.J.P. is a NIHR Senior Investigator. 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. We thank the volunteers who participated in this study. We thank P. B. Gilbert and P. Dull for their advice and contributions to the methodology. The authors appreciate the efforts of the Labcorp-Monogram Biosciences Clinical Reference Laboratory.

Publisher Copyright:
© 2021, The Author(s).

Keywords

  • NCOV-19 AZD1222 VACCINE
  • COVID-19
  • EFFICACY
  • IMMUNITY

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