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Cited by 131SARS-CoV-2 and COVID-19 ResearchVaccine Coverage and HesitancyImmune responses and vaccinations

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Quantitative SARS-CoV-2 anti-spike responses to Pfizer–BioNTech and Oxford–AstraZeneca vaccines by previous infection status

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Eyre, David W., Lumley, Sheila F., Wei, Jia, Cox, Stuart, James, Tim, Justice, Anita, Jesuthasan, Gerald, O'Donnell, Denise, Howarth, Alison, Hatch, Stephanie B., Marsden, Brian D., Jones, E. Yvonne, Stuart, David I., Ebner, Daniel, Hoosdally, Sarah, Crook, Derrick W., Peto, Tim E.A., Walker, Timothy M., Stoesser, Nicole E., Matthews, Philippa C., Pouwels, Koen B., Walker, A. Sarah, Jeffery, Katie·2021·Clinical Microbiology and Infection
DOI 10.1016/j.cmi.2021.05.041PMC PMC8180449

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Abstract

OBJECTIVES: We investigated determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike IgG responses in healthcare workers (HCWs) following one or two doses of Pfizer-BioNTech or Oxford-AstraZeneca vaccines. METHODS: HCWs participating in regular SARS-CoV-2 PCR and antibody testing were invited for serological testing prior to first and second vaccination, and 4 weeks post-vaccination if receiving a 12-week dosing interval. Quantitative post-vaccination anti-spike antibody responses were measured using the Abbott SARS-CoV-2 IgG II Quant assay (detection threshold: ≥50 AU/mL). We used multivariable logistic regression to identify predictors of seropositivity and generalized additive models to track antibody responses over time. RESULTS: 3570/3610 HCWs (98.9%) were seropositive >14 days post first vaccination and prior to second vaccination: 2706/2720 (99.5%) were seropositive after the Pfizer-BioNTech and 864/890 (97.1%) following the Oxford-AstraZeneca vaccines. Previously infected and younger HCWs were more likely to test seropositive post first vaccination, with no evidence of differences by sex or ethnicity. All 470 HCWs tested >14 days after the second vaccination were seropositive. Quantitative antibody responses were higher after previous infection: median (IQR) >21 days post first Pfizer-BioNTech 14 604 (7644-22 291) AU/mL versus 1028 (564-1985) AU/mL without prior infection (p < 0.001). Oxford-AstraZeneca vaccine recipients had lower readings post first dose than Pfizer-BioNTech recipients, with and without previous infection, 10 095 (5354-17 096) and 435 (203-962) AU/mL respectively (both p < 0.001 versus Pfizer-BioNTech). Antibody responses >21 days post second Pfizer vaccination in those not previously infected, 10 058 (6408-15 582) AU/mL, were similar to those after prior infection followed by one vaccine dose. CONCLUSIONS: SARS-CoV-2 vaccination leads to detectable anti-spike antibodies in nearly all adult HCWs. Whether differences in response impact vaccine efficacy needs further study.

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Figures

Fig. 1 Anti-spike IgG-positive results by days since first vaccination, by prior infection status and vaccine received. Tests performed after a second dose of vaccine are not included. The number of tests performed and positive and the resulting percentage is shown under each bar.
Fig. 1 Anti-spike IgG-positive results by days since first vaccination, by prior infection status and vaccine received. Tests performed after a second dose of vaccine are not included. The number of tests performed and positive and the resulting percentage is shown under each bar.CC BY · PubMed Central
Fig. 2 The relationship between vaccine, age and probability of testing anti-spike IgG seropositive >14 days post first vaccination. Model predictions are shown using reference categories for sex and ethnicity (white, female, respectively) and in those without prior evidence of infection.
Fig. 2 The relationship between vaccine, age and probability of testing anti-spike IgG seropositive >14 days post first vaccination. Model predictions are shown using reference categories for sex and ethnicity (white, female, respectively) and in those without prior evidence of infection.CC BY · PubMed Central
Fig. 3 Modelled quantitative anti-spike IgG responses following first vaccination by vaccine and previous infection status. Panels A and B show responses in previously infected healthcare workers (HCWs) and panels C and D HCWs without evidence of previous infection. Panels A and C show data for those receiving Pfizer–BioNTech vaccine and panels B and D Oxford–AstraZeneca vaccine. Model predictions are shown at three example ages: 30, 45, and 60 years. The shaded ribbon shows the 95% confidence interval. Values are plotted from 7 days prior to vaccination to illustrate baseline values (models are fitted using data from 28 days prior to vaccination onwards).
Fig. 3 Modelled quantitative anti-spike IgG responses following first vaccination by vaccine and previous infection status. Panels A and B show responses in previously infected healthcare workers (HCWs) and panels C and D HCWs without evidence of previous infection. Panels A and C show data for those receiving Pfizer–BioNTech vaccine and panels B and D Oxford–AstraZeneca vaccine. Model predictions are shown at three example ages: 30, 45, and 60 years. The shaded ribbon shows the 95% confidence interval. Values are plotted from 7 days prior to vaccination to illustrate baseline values (models are fitted using data from 28 days prior to vaccination onwards).CC BY · PubMed Central
Fig. 4 Modelled quantitative anti-spike IgG titres following second Pfizer–BioNTech vaccination by previous infection status. Panel A shows those who were previous infected (including those previously infected at baseline or testing PCR-positive between vaccines) and panel B those who had no evidence of previous infection. Model predictions are shown at three example ages: 30, 45, and 60 years. The shaded ribbon shows the 95% confidence interval. Data were included in each model from 7 days before the second vaccination to allow pre-vaccination levels to be fitted correctly.
Fig. 4 Modelled quantitative anti-spike IgG titres following second Pfizer–BioNTech vaccination by previous infection status. Panel A shows those who were previous infected (including those previously infected at baseline or testing PCR-positive between vaccines) and panel B those who had no evidence of previous infection. Model predictions are shown at three example ages: 30, 45, and 60 years. The shaded ribbon shows the 95% confidence interval. Data were included in each model from 7 days before the second vaccination to allow pre-vaccination levels to be fitted correctly.CC BY · PubMed Central

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Research works printed but not linked: 4

  1. Walsh, 2020, Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates, N Engl J Med, 383, 2439, 10.1056/NEJMoa2027906 · DOI · Paper page
  2. Saadat, 2021, Single dose vaccination in healthcare workers previously infected with SARS-CoV-2, medRxiv
  3. Pritchard, 2021, Impact of vaccination on SARS-CoV-2 cases in the community: a population-based study using the UK’s COVID-19 Infection Survey, medRxiv, 4
  4. Monin-Aldama, 2021, Interim results of the safety and immune-efficacy of 1 versus 2 doses of COVID-19 vaccine BNT162b2 for cancer patients in the context of the UK vaccine priority guidelines, bioRxiv, vol. 3

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Metadata

Authors
Eyre, D. W., Lumley, S. F., Wei, J., Cox, S., James, T., Justice, A., Jesuthasan, G., O'Donnell, D., Howarth, A., Hatch, S. B., Marsden, B. D., Jones, E. Y., Stuart, D. I., Ebner, D., Hoosdally, S., Crook, D. W., Peto, T. E. A., Walker, T. M., Stoesser, N. E., Matthews, P. C., Pouwels, K. B., Walker, A. S., & Jeffery, K.
Affiliations
  • Public Health England (GB)
  • University of Oxford (GB)
  • Oxford University Hospitals NHS Trust (GB)
Corresponding author
Eyre, David W.
ORCID
Venue
Clinical Microbiology and Infection
Publisher
Elsevier BV
Published
2021-10
Volume
27
Issue
10
Pages
1516.e7-1516.e14
ISSN
1198-743X (ISSN-L)
DOI
10.1016/j.cmi.2021.05.041
PMC
PMC8180449
OpenAlex
W3170306142
Cited by
131
References
25
Citations by year
2025: 4 · 2024: 13 · 2023: 11 · 2022: 76 · 2021: 27
FWCI
10.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Microbiology and Infection (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Institute for Health Research
  • United Kingdom Department of Health and Social Care
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Social Sciences › Health › Vaccine Coverage and Hesitancy
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords
SARS-CoV-2, COVID-19 vaccines, anti-spike IgG, prior SARS-CoV-2 infection, hybrid immunity, BNT162b2, Oxford-AstraZeneca vaccine, healthcare workers, seropositivity, antibody kinetics, vaccine dosing interval, ChAdOx1 nCoV-19 vaccine, SARS-CoV-2 spike protein
MeSH terms
Immunogenicity, Vaccine, COVID-19, SARS-CoV-2, COVID-19 Vaccines, BNT162 Vaccine, ChAdOx1 nCoV-19, Adult, Antibodies, Viral, Female, Health Personnel, Humans, Immunoglobulin G, Male, Middle Aged, Vaccination, Spike Glycoprotein, Coronavirus

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