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

David W Eyre ,Stephanie B Hatch,Timothy M Walker,Katie Jeffery,Alison Howarth,Philippa C Matthews,Daniel Ebner,Jia Wei,Tim James,Stuart Cox,Sarah Hoosdally,Derrick W Crook,Brian D Marsden,Gerald Jesuthasan,Anita Justice,Nicole Stoesser ,A Sarah Walker ,Elizabeth Jones ,Denise O’donnell ,Sheila F Lumley ,Tim Peto ,Koen B Pouwels ,D.i Stuart

doi:10.1016/j.cmi.2021.05.041

Abstract

ObjectivesWe 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. MethodsHCWs 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. Results3570/3610 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. ConclusionsSARS-CoV-2 vaccination leads to detectable anti-spike antibodies in nearly all adult HCWs. Whether differences in response impact vaccine efficacy needs further study.

Highlights

As vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are rolled out globally, individuals and their clinicians may wish to seek reassurance that vaccination has been ‘effective’ and to understand how long protection is likely to last
Fewer healthcare workers (HCWs) were seropositive after a first dose of OxfordeAstraZeneca compared to PfizereBioNTech vaccine, with the difference more marked as age increased
PfizereBioNTech vaccine resulted in higher antibody readings than the OxfordeAstraZeneca vaccine in both those with and those without previous infection, over two-fold higher if not previously infected

Summary

Introduction

As vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are rolled out globally, individuals and their clinicians may wish to seek reassurance that vaccination has been ‘effective’ and to understand how long protection is likely to last. Understanding the assay- and time-dependent dynamics of post-vaccination antispike antibody measurements, how they differ between individuals (e.g. by age, gender, ethnicity, and with comorbidities), and how these findings relate to protection are increasingly important. The dynamics and magnitude of the immune response seen in vaccine immunogenicity trials are assay-dependent, predominantly focus on individuals without previous SARS-CoV-2 infection, and use in-house assays developed early in the pandemic rather than the commercially available, validated assays accessible to diagnostic laboratories [1,5e8]. Emerging real-world data show that most individuals vaccinated with the mRNA vaccines PfizereBioNTech BNT162b2 and Moderna mRNA-1273 seroconvert by 21 days post first vaccine dose, with more rapid seroconversion and higher antibody titres seen in individuals previously infected with SARS-CoV-2 (using in-house ELISAs, and two commercial platforms) [9e12]. No trials have published data on whether measured immune markers correspond to observed vaccine efficacy (i.e. protection from infection, hospitalization or death)

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