Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection
Open accessAbstract
Background: Although 6 COVID-19 vaccines have been approved by the World Health Organisation as of 16 th June 2021, global supply remains limited. An understanding of the immune response associated with protection could facilitate rapid licensure of new vaccines. Methods: Data from a randomised efficacy trial of ChAdOx1 nCoV-19 (AZD1222) vaccine in the UK was analysed to determine the antibody levels associated with protection against SARS-CoV-2. Anti-spike and anti-RBD IgG by multiplex immunoassay, pseudovirus and live neutralising antibody at 28 days after the second dose were measured in infected and non-infected vaccine recipients. Weighted generalised additive models for binary data were applied to symptomatic and asymptomatic SARS-CoV-2 infection data from ChAdOx1 nCoV-19 recipients. Cubic spline smoothed log antibody levels, and weights were applied to account for potential selection bias in sample processing. Models were adjusted for baseline risk of exposure to SARS-CoV-2 infection. Results: Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. Vaccine efficacy of 80% against primary symptomatic COVID-19 was achieved with an antibody level of 40923 (95% CI: 16748, 125017) and 63383 (95% CI: 16903, not computed (NC)) for anti-spike and anti-RBD, and 185 (95% CI: NC, NC) and 247 (95% CI: 101, NC) for pseudo- and live-neutralisation assays respectively. Antibody responses did not correlate with overall protection against asymptomatic infection. Conclusions: Correlates of protection can be used to bridge to new populations using validated assays. The data can be used to extrapolate efficacy estimates for new vaccines where large efficacy trials cannot be conducted. More work is needed to assess correlates for emerging variants.
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There is increasing evidence that neutralizing responses are a correlate of protection.
“There is increasing evidence that neutralizing responses are a correlate of protection [4][5][6] .”
From Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2 (2021) · cites this paper as [6]
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- Authors
- Feng, S., Phillips, D. J., White, T., Sayal, H., Aley, P. K., Bibi, S., Dold, C., Fuskova, M., Gilbert, S. C., Hirsch, I., Humphries, H. E., Jepson, B., Kelly, E. J., Plested, E., Shoemaker, K., Thomas, K. M., Vekemans, J., Villafana, T. L., Lambe, T., Pollard, A. J., Voysey, M., & the Oxford COVID Vaccine Trial Group
- Affiliations
- University of Oxford (GB)
- AstraZeneca (United Kingdom) (GB)
- Public Health England (GB)
- AstraZeneca (United States) (US)
- AstraZeneca (Sweden) (SE)
- Corresponding author
- Voysey, Merryn
- ORCID
- Venue
- Nature Medicine
- Publisher
- openRxiv
- Published
- 2021-06-24
- Volume
- 27
- Issue
- 11
- Pages
- 2032-2040
- ISSN
- 1078-8956 (ISSN-L)
- PMC
- PMC8604724
- OpenAlex
- W3174017401
- Cited by
- 1,163
- References
- 1
- Citations by year
- 2026: 36 · 2025: 94 · 2024: 155 · 2023: 255 · 2022: 515 · 2021: 106 · 2020: 1
- FWCI
- 81.72
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Nature Medicine (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (publishedVersion, cc-by)
- St George's Online Research Archive (St George's University of London) (acceptedVersion)
- LSTM Online Archive (Liverpool School of Tropical Medicine) (acceptedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- Liverpool John Moores University (acceptedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Funders
- AstraZeneca
- Wellcome Trust (211153/Z/18/Z)
- UK Research and Innovation (MC_PC_19055)
- Coalition for Epidemic Preparedness Innovations
- National Institute for Health and Care Research (NF-SI-0617-10036, OxfordVacc-01, COV19OxfordVaccine01, MC_PC_19055)
- Department of Health and Social Care
- Medical Research Council (MC_UU_00004/04)
- Engineering and Physical Sciences Research Council (EP/R013756/1)
- NIHR Oxford Biomedical Research Centre
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV-2, COVID-19 vaccines, vaccine efficacy, binding antibodies, neutralizing antibodies, anti-spike antibodies, anti-RBD antibodies, pseudovirus neutralization, symptomatic infection, asymptomatic infection, Alpha variant, vaccine correlates of protection, vaccine licensure
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Viral, Female, United Kingdom, Humans, Immunization, Secondary, Male, Middle Aged, Vaccination, Cohort Studies, Treatment Outcome, Infection Control, Young Adult, Immunity, Humoral, Antibodies, Neutralizing, Asymptomatic Infections, Patient Acuity
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