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; Sagida Bibi; Parvinder K Aley; Federica Cappuccini; Elizabeth A Clutterbuck; Kerry Conlin; Narges Ebrahimi; Agnes Eordogh; Saul N Faust; Sally Felle; Justin Green; Hardeep Gill; Yama Mujadidi; Iyiola Oladunjoye; Nelly Owino; Emma Plested; Hannah Robinson; Arabella Stuart; Merryn Voysey; Andrew J Pollard; Teresa Lambe

doi:10.1016/j.jinf.2025.106423

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

J Infect. 2025 Jan 16:106423. doi: 10.1016/j.jinf.2025.106423. Online ahead of print.

Authors

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.
² Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK. Electronic address: [email protected].
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 enrolled 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 4^th dose had stronger responses to a 4^th 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.