Towards a population-based threshold of protection for COVID-19 vaccines

David Goldblatt; Andrew Fiore-Gartland; Marina Johnson; Adam Hunt; Christopher Bengt; Dace Zavadska; Hilda Darta Snipe; Jeremy S Brown; Lesley Workman; Heather J Zar; David Montefiori; Xiaoying Shen; Peter Dull; Stanley Plotkin; George Siber; Donna Ambrosino

doi:10.1016/j.vaccine.2021.12.006

Towards a population-based threshold of protection for COVID-19 vaccines

Vaccine. 2022 Jan 21;40(2):306-315. doi: 10.1016/j.vaccine.2021.12.006. Epub 2021 Dec 15.

Authors

David Goldblatt¹, Andrew Fiore-Gartland², Marina Johnson³, Adam Hunt³, Christopher Bengt³, Dace Zavadska⁴, Hilda Darta Snipe⁴, Jeremy S Brown⁵, Lesley Workman⁶, Heather J Zar⁶, David Montefiori⁷, Xiaoying Shen⁷, Peter Dull⁸, Stanley Plotkin⁹, George Siber¹⁰, Donna Ambrosino¹¹

Affiliations

¹ Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1 EH, UK; Great Ormond Street Children's Hospital NHS Foundation Trust, Great Ormond Street, London WC1N 3JH, UK. Electronic address: [email protected].
² Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
³ Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1 EH, UK.
⁴ Children's Clinical University Hospital, Vienibas gatve 45, Riga LV-1004, Latvia.
⁵ UCL Respiratory, Division of Medicine, University College London, London WC1E 6JF, UK.
⁶ Dept of Paediatrics & Child Health, Red Cross Children's Hospital, and SA-MRC Unit on Child & Adolescent Health, University of Cape Town, South Africa.
⁷ Department of Surgery, Duke University Medical Center, Durham, NC, USA.
⁸ Vaccine Development and Surveillance, Bill & Melinda Gates Foundation, Seattle, WA, USA.
⁹ Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹⁰ Independent Advisor, New York, NY, USA.
¹¹ Independent Advisor, Stuart, FL, USA.

Abstract

Correlates of protection for COVID-19 vaccines are urgently needed to license additional vaccines. We measured immune responses to four COVID-19 vaccines of proven efficacy using a single serological platform. IgG anti-Spike antibodies were highly correlated with ID50 neutralization in a validated pseudoviral assay and correlated significantly with efficacies for protection against infection with wild-type, alpha and delta variant SARS-CoV-2 virus. The protective threshold for each vaccine was calculated for IgG anti-Spike antibody. The mean protective threshold for all vaccine studies for WT virus was 154 BAU/ml (95 %CI 42-559), and for studies with antibody distributions that enabled precise estimation of thresholds (i.e. leaving out 2-dose mRNA regimens) was 60 BAU/ml (95 %CI 35-102). We propose that the proportion of individuals with responses above the appropriate protective threshold together with the geometric mean concentration can be used in comparative non-inferiority studies with licensed vaccines to ensure that new vaccines will be efficacious.

Keywords: COVID vaccines; COVID-19; Correlates of protection; SARS-CoV-2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
COVID-19*
Humans
SARS-CoV-2*
Spike Glycoprotein, Coronavirus

Substances

Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
Spike Glycoprotein, Coronavirus

Supplementary concepts

SARS-CoV-2 variants

Grants and funding

MR/V028782/1/MRC_/Medical Research Council/United Kingdom