Safety and humoral immunogenicity of the ChAdOx1 nCoV-19 vaccine administered as a fourth dose booster following two doses of ChAdOx1 nCoV-19 and a third dose of BNT162b2 (COV009): A prospective cohort study

Shuo Feng¹, Sagida Bibi², Parvinder K Aley³, Federica Cappuccini³, Elizabeth A Clutterbuck³, Kerry Conlin³, Narges Ebrahimi³, Agnes Eordogh³, Saul N Faust⁴, Sally Felle³, Justin Green⁵, Hardeep Gill³, Yama Mujadidi³, Iyiola Oladunjoye⁶, Nelly Owino³, Emma Plested³, Hannah Robinson³, Arabella Stuart³, Merryn Voysey³, Andrew J Pollard⁷, Teresa Lambe⁸

Affiliations

¹ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK; Department of Epidemiology and Biostatistics, Tongji Medical College, Huazhong University of Science and Technology, China.
² Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK. Electronic address: sagida.bibi@paediatrics.ox.ac.uk.
³ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
⁴ NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Trust, UK; Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK.
⁵ Vaccines and Immune Therapies Biopharmaceuticals R&D, AstraZeneca, Cambridge, UK.
⁶ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
⁷ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK; Pandemic Sciences Institute, University of Oxford, Oxford, UK.
⁸ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK; Pandemic Sciences Institute, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute, University of Oxford, Oxford, UK.

PMID: 39826861
DOI: 10.1016/j.jinf.2025.106423

Free article

Safety and humoral immunogenicity of the ChAdOx1 nCoV-19 vaccine administered as a fourth dose booster following two doses of ChAdOx1 nCoV-19 and a third dose of BNT162b2 (COV009): A prospective cohort study

Shuo Feng et al. J Infect. 2025 Feb.

Free article

. 2025 Feb;90(2):106423.

doi: 10.1016/j.jinf.2025.106423. Epub 2025 Jan 16.

Authors

Affiliations

¹ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK; Department of Epidemiology and Biostatistics, Tongji Medical College, Huazhong University of Science and Technology, China.
² Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK. Electronic address: sagida.bibi@paediatrics.ox.ac.uk.
³ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
⁴ NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Trust, UK; Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK.
⁵ Vaccines and Immune Therapies Biopharmaceuticals R&D, AstraZeneca, Cambridge, UK.
⁶ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
⁷ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK; Pandemic Sciences Institute, University of Oxford, Oxford, UK.
⁸ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK; Pandemic Sciences Institute, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute, University of Oxford, Oxford, UK.

PMID: 39826861
DOI: 10.1016/j.jinf.2025.106423

Abstract

Objectives: Evaluation of the safety and humoral immunogenicity of ChAdOx1 nCoV-19 as a fourth dose booster in individuals who have had two initial doses of the vaccine and a third dose of BNT162b2.

Methods: COV009 is a safety follow-up study of volunteers enroled in the pivotal pre-licensure ChAdOx1 nCoV-19. In this sub-study, 149 eligible participants were given a fourth dose of ChAdOx1 nCoV-19. Primary outcomes were reactogenicity, safety, and humoral immunogenicity. Anti-spike IgG and pseudo-neutralising antibody against multiple variants were measured from pre-first dose to 28 days post-second and post-fourth dose (third dose samples were unavailable).

Results: A fourth dose of ChAdOx1 nCoV-19 had an acceptable safety profile with no vaccine-related serious adverse events. Humoral responses against various SARS CoV-2 variants post-fourth dose were significantly increased compared with the responses after the second dose (7- to 9-fold increase for anti-spike IgG responses across variants, all p<0.05). Those with lower antibody levels prior to the 4th dose had stronger responses to a 4th dose booster. Seropositivity by anti-nucleocapsid, or higher antibody responses pre-fourth dose correlated with lower infection risks six months thereafter (OR: 0.16, 95% CI: 0.05, 0.50).

Conclusions: The ChAdOx1 nCoV-19 fourth dose is well tolerated and boosts humoral immunity; this was evident as an increased humoral response across multiple variants of concern. These data support its use as a booster dose against SARS-CoV-2 infection.

Keywords: COVID-19 vaccine; ChAdOx1 nCoV-19; Fourth Dose; Immunogenicity; Safety.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AJP is Chair of the UK DHSC Joint on Vaccination & Immunisation (JCVI) but did not participate in the JCVI COVID19 committee during the pandemic and was a member of the Strategic Advisory Group of Experts on Immunization to the WHO (World Health Organization) until 2022. TL reports consulting fees from Vaccitech on an unrelated project, an honorarium from Seqirus, grant support from the Vaccine Taskforce for this trial, work-related investments, and is named as an inventor on a patent application for a vaccine against SARS-CoV-2. JG is an employee of, and holds stocks in, AstraZeneca. AJP, TL, SB, PA, FC, EC, SF, YM, NO, EP, HR, AS, and MV are inventors and/or contributors to the intellectual property licensed by Oxford University Innovation to AstraZeneca. All other authors declare no competing interests. The views expressed in this article do not necessarily represent the views of the funders.

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Safety and humoral immunogenicity of the ChAdOx1 nCoV-19 vaccine administered as a fourth dose booster following two doses of ChAdOx1 nCoV-19 and a third dose of BNT162b2 (COV009): A prospective cohort study

Affiliations

Safety and humoral immunogenicity of the ChAdOx1 nCoV-19 vaccine administered as a fourth dose booster following two doses of ChAdOx1 nCoV-19 and a third dose of BNT162b2 (COV009): A prospective cohort study

Authors

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Abstract

Conflict of interest statement

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Medical

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