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

Journal article

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.

Authors: Feng, S; Bibi, S; Aley, PK; Cappuccini, F; Clutterbuck, EA

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Journal of Infection
• Volume: 90
• Issue: 2
• Article number: 106423
• Place of publication: England
• Publication date: 2025-01-16
• Acceptance date: 2025-01-13
• DOI: 10.1016/j.jinf.2025.106423
• EISSN: 1532-2742
• ISSN: 0163-4453
• Pmid: 39826861
• Language: English
• Keywords: COVID-19 vaccine; immunogenicity; safety; fourth dose; ChAdOx1 nCoV-19