Serological responses and vaccine effectiveness for extended COVID-19 vaccine schedules in England

Gayatri Amirthalingam,Georgina Ireland,Kevin E Brown,Paul Moss,Corinne Whillock,Nick J Andrews,Jamie Lopez Bernal,Sathyavani Subbarao,Shamez N Ladhani,Elise Tessier,Lenesha Warrener,Michelle O’Brien,Ezra Linley,Charlotte Gower,Mary E Ramsay,Frances Baawuah,Julia Stowe,Heather Whitaker

doi:10.1038/s41467-021-27410-5

Gayatri Amirthalingam, Georgina Ireland + Show 16 more

Open Access

https://doi.org/10.1038/s41467-021-27410-5

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Abstract

The UK prioritised delivery of the first dose of BNT162b2 (Pfizer/BioNTech) and AZD1222 (AstraZeneca) vaccines by extending the interval between doses up to 12 weeks. In 750 participants aged 50–89 years, we here compare serological responses after BNT162b2 and AZD1222 vaccination with varying dose intervals, and evaluate these against real-world national vaccine effectiveness (VE) estimates against COVID-19 in England. We show that antibody levels 14–35 days after dose two are higher in BNT162b2 recipients with an extended vaccine interval (65–84 days) compared with those vaccinated with a standard (19–29 days) interval. Following the extended schedule, antibody levels were 6-fold higher at 14–35 days post dose 2 for BNT162b2 than AZD1222. For both vaccines, VE was higher across all age-groups from 14 days after dose two compared to one dose, but the magnitude varied with dose interval. Higher dose two VE was observed with >6 week interval between BNT162b2 doses compared to the standard schedule. Our findings suggest higher effectiveness against infection using an extended vaccine schedule. Given global vaccine constraints these results are relevant to policymakers.

Highlights

The UK prioritised delivery of the first dose of BNT162b2 (Pfizer/BioNTech) and AZD1222 (AstraZeneca) vaccines by extending the interval between doses up to 12 weeks
In the United Kingdom, older adults were prioritised for vaccination at the start of the COVID-19 immunisation programme on 08 December 2020, initially with the Pfizer/BioNTech (BNT162b2) vaccine using the authorised 3-week interval between doses[4]
The decision to extend the second dose was based on early clinical trial data indicating nearly 90% effectiveness against SARS-CoV-2 within 3 weeks of the first dose of BNT162b2 vaccine compared to 95% from two weeks after the second dose[6]

Summary

Introduction

The UK prioritised delivery of the first dose of BNT162b2 (Pfizer/BioNTech) and AZD1222 (AstraZeneca) vaccines by extending the interval between doses up to 12 weeks. In 750 participants aged [50–89] years, we here compare serological responses after BNT162b2 and AZD1222 vaccination with varying dose intervals, and evaluate these against real-world national vaccine effectiveness (VE) estimates against COVID-19 in England. Vaccinating more at-risk individuals quickly with a single dose was predicted to prevent more cases, hospitalisations and deaths than two doses at a 3-week interval[7] This unique approach against authorised use and without formal clinical trials resulted in considerable international debate and prompted the need to evaluate immune responses and vaccine effectiveness following extended schedules. We report serological responses in 750 adults aged [50–89] years given two doses of BNT162b2 or AZD1222 at different intervals, comparing serological responses These findings are evaluated against real-world vaccine effectiveness estimates against COVID-19 using similar dosing intervals in the same age group in England

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