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Determinants of Antibody Responses to Two Doses of ChAdOx1 nCoV-19 or Bnt162b2 and a Subsequent Booster Dose of BNT162b2 or mRNA-1273: Population-Based Cohort Study (COVIDENCE UK)

36 Pages Posted: 3 Mar 2022

See all articles by David Jolliffe

David Jolliffe

Queen Mary University of London

Sian Faustini

University of Birmingham - Institute of Cancer and Genomic Sciences; University of Birmingham - Clinical Immunology Service

Hayley Holt

Queen Mary University of London - Institute of Population Health Sciences

Natalia Perdek

Queen Mary University of London

Sheena Maltby

Queen Mary University of London

Mohammad Talaei

Queen Mary University of London - Institute of Population Health Sciences

Matthew Greenig

Queen Mary University of London

Giulia Vivaldi

Queen Mary University of London

Florence Tydeman

Queen Mary University of London

Jane Symons

Jane Symons Media

Gwyneth A. Davies

Swansea University - Swansea University Medical School

Ronan A. Lyons

Swansea University - Population Data Science

Christopher J. Griffiths

Queen Mary University of London - Institute of Population Health Sciences

Frank Kee

Queen's University Belfast

Aziz Sheikh

University of Edinburgh - Asthma UK Centre for Applied Research

Seif O. Shaheen

Queen Mary University of London - Institute of Population Health Sciences

Alex G. Richter

University of Birmingham - Institute of Cancer and Genomic Sciences; University of Birmingham - Clinical Immunology Service

Adrian R. Martineau

Queen Mary University of London - Barts and The London School of Medicine and Dentistry; Queen Mary University of London - Institute of Population Health Sciences; Queen Mary University of London - Asthma UK Centre for Applied Research

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Abstract

Background: Antibody responses to SARS-CoV-2 vaccination vary for reasons that remain poorly understood. 

Methods: We tested for presence of combined IgG, IgA and IgM (IgGAM) anti-spike antibodies before and after administration of two doses of ChAdOx1 nCoV-19 (ChAdOx1, Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech) in UK adults participating in a population-based longitudinal study who received their first dose of vaccine from December 15, 2020 to July 10, 2021. Information on sixty-six potential sociodemographic, behavioural, clinical, pharmacological and nutritional determinants of serological response to vaccination was captured using serial online questionnaires. We used logistic regression to estimate multivariable-adjusted odds ratios (aORs) for associations between independent variables and risk of seronegativity following two vaccine doses. Participants who were seronegative after receiving two vaccine doses were offered an additional antibody test following subsequent administration of a ‘booster’ dose of BNT162b2 or mRNA-1273 (Moderna) from September 23 to December 12, 2021. 

Findings: Serology results following two vaccine doses were available for 9,101 participants, of whom 5,770 (63.4%) received ChAdOx1 and 3,331 (36.6%) received BNT162b2. Anti-spike IgGAM was undetectable in 378 (4.2%) participants at a median of 8.6 weeks (IQR 6.4-10.7 weeks) after their second dose of vaccine. Seronegativity following two doses of SARS-CoV-2 vaccination was associated with administration of ChAdOx1 vs BNT162b2 (aOR 7.03, 95% CI 4.39-11.24), shorter interval between first and second vaccine doses (aOR 2.37, 1.06-5.26, for <6 weeks vs >10 weeks; aOR 1.59, 1.18-2.13, for 6-10 weeks vs >10 weeks), poorer self-assessed general health (aOR 3.33, 1.49-7.46, for poor vs excellent), immunodeficiencies (aOR 6.75, 2.63-17.35) and prescription of systemic immunosuppressants (aOR 3.76, 2.44-5.78). By contrast, pre-vaccination SARS-CoV-2 seropositivity (aOR 0.16, 0.04-0.70, for symptomatic seropositives vs seronegatives) and supplemental vitamin D intake (aOR 0.73, 0.53-0.99) were associated with reduced risk of post-vaccination seronegativity. 247/378 (65.3%) of participants who were seronegative after two doses of ChAdOx1 vs BNT162b2 provided a third sample at a median of 7.8 weeks (IQR 5.8-10.4) after receiving a booster dose of BNT162b2 or mRNA-1273: eight (3.2%) of them remained seronegative after three vaccine doses, all of whom either had a primary immunodeficiency or were taking systemic immunosuppressant drugs.

Interpretation: We identify multiple determinants of antibody responses to two doses of ChAdOx1 or BNT162b2, many of which are potentially modifiable. Booster doses of BNT162b2 or mRNA-1273 were highly effective in achieving seroconversion in those who failed to mount antibody responses following two doses of ChAdOx1 or BNT162b2.

Trial Registration Details: Registered with ClinicalTrials.gov (NCT04330599).

Funding Information: This study was supported by a grant from Barts Charity to ARM and CJG (MGU0466) and by donations to Queen Mary University of London from the Fischer Family Trust, the Exilarch’s Foundation and DSM Nutritional Products Ltd. DAJ is supported by a Barts Charity Lectureship (MGU0459). MT is supported by a grant from the Rosetrees Trust and The Bloom Foundation (M771). The work was carried out with the support 20 of BREATHE - The Health Data Research Hub for Respiratory Health (MC_PC_19004) in partnership with SAIL Databank. BREATHE is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK.

Declaration of Interests: JS declares receipt of payments from Reach plc for news stories written about recruitment to, and findings of, the COVIDENCE UK study. AS is a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group and its Standing Committee on Pandemics. He is also a member of the UK Government’s NERVTAG’s Risk Stratification Subgroup. ARM declares receipt of funding in the last 36 months to support vitamin D research from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd, DSM Nutritional Products Ltd, Thornton & Ross Ltd and Hyphens Pharma Ltd. ARM also declares support for attending meetings from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd and Abiogen Pharma Ltd. ARM also declares participation on the Data and Safety Monitoring Board for the Chair, DSMB, VITALITY trial (Vitamin D for Adolescents with HIV to reduce musculoskeletal morbidity and immunopathology). ARM also declares unpaid work as a Programme Committee member for the Vitamin D Workshop. ARM also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord Ltd, Synergy Biologics Ltd and Cytoplan Ltd. All other authors have nothing to declare.

Ethics Approval Statement: Approved by Leicester South Research Ethics Committee (ref 20/EM/0117).

Keywords: SARS-CoV-2 vaccine, ChAdOx1, BNT162b2, mRNA-1273, antibody, ethnicity, obesity, vitamin D

Suggested Citation

Jolliffe, David and Faustini, Sian and Holt, Hayley and Perdek, Natalia and Maltby, Sheena and Talaei, Mohammad and Greenig, Matthew and Vivaldi, Giulia and Tydeman, Florence and Symons, Jane and Davies, Gwyneth A. and Lyons, Ronan A. and Griffiths, Christopher J. and Kee, Frank and Sheikh, Aziz and Shaheen, Seif O. and Richter, Alex G. and Martineau, Adrian R., Determinants of Antibody Responses to Two Doses of ChAdOx1 nCoV-19 or Bnt162b2 and a Subsequent Booster Dose of BNT162b2 or mRNA-1273: Population-Based Cohort Study (COVIDENCE UK). Available at SSRN: https://ssrn.com/abstract=4031570 or http://dx.doi.org/10.2139/ssrn.4031570

David Jolliffe

Queen Mary University of London ( email )

Mile End Road
London, E1 4NS
United Kingdom

Sian Faustini

University of Birmingham - Institute of Cancer and Genomic Sciences

Birmingham
United Kingdom

University of Birmingham - Clinical Immunology Service ( email )

United Kingdom

Hayley Holt

Queen Mary University of London - Institute of Population Health Sciences ( email )

London
United Kingdom

Natalia Perdek

Queen Mary University of London ( email )

Mile End Road
London, E1 4NS
United Kingdom

Sheena Maltby

Queen Mary University of London ( email )

Mile End Road
London, E1 4NS
United Kingdom

Mohammad Talaei

Queen Mary University of London - Institute of Population Health Sciences ( email )

London
United Kingdom

Matthew Greenig

Queen Mary University of London ( email )

Mile End Road
London, E1 4NS
United Kingdom

Giulia Vivaldi

Queen Mary University of London ( email )

Mile End Road
London, E1 4NS
United Kingdom

Florence Tydeman

Queen Mary University of London ( email )

Mile End Road
London, E1 4NS
United Kingdom

Jane Symons

Jane Symons Media ( email )

London
United Kingdom

Gwyneth A. Davies

Swansea University - Swansea University Medical School ( email )

Singleton Park
Swansea, Wales SA2 8PP
United Kingdom

Ronan A. Lyons

Swansea University - Population Data Science ( email )

Christopher J. Griffiths

Queen Mary University of London - Institute of Population Health Sciences ( email )

London
United Kingdom

Frank Kee

Queen's University Belfast ( email )

Aziz Sheikh

University of Edinburgh - Asthma UK Centre for Applied Research ( email )

Edinburgh
United Kingdom

Seif O. Shaheen

Queen Mary University of London - Institute of Population Health Sciences ( email )

London
United Kingdom

Alex G. Richter

University of Birmingham - Institute of Cancer and Genomic Sciences ( email )

Edgbaston
Birminham, Birmingham B152TT
United Kingdom

University of Birmingham - Clinical Immunology Service ( email )

Birmingham
United Kingdom

Adrian R. Martineau (Contact Author)

Queen Mary University of London - Barts and The London School of Medicine and Dentistry ( email )

Blizard Institute
4 Newark St.
London, E1 2AT
United Kingdom
+44 207 882 2551 (Phone)
+44 207 882 2552 (Fax)

Queen Mary University of London - Institute of Population Health Sciences ( email )

London
United Kingdom
+44 207 882 2551 (Phone)
+44 207 882 2552 (Fax)

Queen Mary University of London - Asthma UK Centre for Applied Research

London
United Kingdom

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