Immunogenicity and Safety of ChAdOx1 nCoV-19 (AZD1222) as a Homologous Fourth-Dose Booster: A Substudy of the Phase 3 COV003 Trial in Brazil
Objective: To address that, despite widespread use of ChAdOx1 nCoV-19 (AZD1222) as a COVID-2019 booster, fourth-dose clinical outcomes data are limited. We report immunogenicity and safety for ChAdOx1 nCoV-19 as a homologous fourth-dose booster. Participants and Methods: Participants (aged ≥18 years...
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Elsevier
2025-08-01
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| Series: | Mayo Clinic Proceedings: Innovations, Quality & Outcomes |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2542454825000530 |
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| author | Sue Ann Costa Clemens, MD, PhD Sagida Bibi, PhD Natalie G. Marchevsky, MSc Parvinder K. Aley, PhD Federica Cappuccini, PhD Sophie A. Davies, BSc Isabela Gonzalez, PhD Sarah C. Kelly, MSc Yama F. Mujadidi, MSc Eveline Pipolo Milan, MD, PhD Alexandre V. Schwarzbold, PhD Eduardo Sprinz, MD, DSc Merryn Voysey, DPhil Lily Y. Weckx, MD, PhD Daniel Wright, DPhil Himanshu Bansal, MS Maria A.S. Bergagård, MSc Abby J. Isaacs, MS Elizabeth J. Kelly, PhD Dongmei Lan, MS Shethah Morgan, PhD Nirmal Kumar Shankar, BAMS Kathryn Shoemaker, MS Tonya L. Villafana, PhD Teresa Lambe, PhD Justin A. Green, MD, PhD Andrew J. Pollard, FMedSci |
| author_facet | Sue Ann Costa Clemens, MD, PhD Sagida Bibi, PhD Natalie G. Marchevsky, MSc Parvinder K. Aley, PhD Federica Cappuccini, PhD Sophie A. Davies, BSc Isabela Gonzalez, PhD Sarah C. Kelly, MSc Yama F. Mujadidi, MSc Eveline Pipolo Milan, MD, PhD Alexandre V. Schwarzbold, PhD Eduardo Sprinz, MD, DSc Merryn Voysey, DPhil Lily Y. Weckx, MD, PhD Daniel Wright, DPhil Himanshu Bansal, MS Maria A.S. Bergagård, MSc Abby J. Isaacs, MS Elizabeth J. Kelly, PhD Dongmei Lan, MS Shethah Morgan, PhD Nirmal Kumar Shankar, BAMS Kathryn Shoemaker, MS Tonya L. Villafana, PhD Teresa Lambe, PhD Justin A. Green, MD, PhD Andrew J. Pollard, FMedSci |
| author_sort | Sue Ann Costa Clemens, MD, PhD |
| collection | DOAJ |
| description | Objective: To address that, despite widespread use of ChAdOx1 nCoV-19 (AZD1222) as a COVID-2019 booster, fourth-dose clinical outcomes data are limited. We report immunogenicity and safety for ChAdOx1 nCoV-19 as a homologous fourth-dose booster. Participants and Methods: Participants (aged ≥18 years) who had received 2 doses of ChAdOx1 nCoV-19 in phase 3 COV003 trial in Brazil were offered a third dose after a planned dose interval from 11 to 13 months and a fourth dose after a planned interval from 6 to 15 months (both 5 × 1010 viral particles). All fourth doses were administered to substudy participants between August 18 and October 28, 2022. The data cutoff was December 9, 2022. The primary immunogenicity outcome was noninferiority of ancestral severe acute respiratory syndrome coronavirus (SARS-CoV)-2–neutralizing antibody responses 28 days after dose 4 versus dose 3. Solicited and unsolicited adverse events were recorded 7 and 28 days postdose 4, respectively. Results: 172 participants received a fourth dose (median interval postthird dose, 10.7 months). Ancestral SARS-CoV-2–neutralizing antibody titers postdose 4 were noninferior to those postdose 3; geometric mean fold rise was 1.9 (95% CI, 1.6-2.4; n=112). Immunogenicity results were consistent across all variants analyzed. Local and systemic solicited adverse events were reported in 60.3% (n=35/58) and 43.1% (n=25/58) of participants, respectively. Conclusion: Immune responses after a fourth dose of ChAdOx1 nCoV-19 were noninferior to those after a third dose across SARS-CoV-2 variants. The fourth dose was well tolerated with no emergent safety concerns, supporting the continued development of the ChAdOx1 platform in preparation for future pandemics. Trial Registration: clinicaltrials.gov Identifier: NCT04536051 |
| format | Article |
| id | doaj-art-e2286db85b8d48e5a7996426f79fd710 |
| institution | Kabale University |
| issn | 2542-4548 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Mayo Clinic Proceedings: Innovations, Quality & Outcomes |
| spelling | doaj-art-e2286db85b8d48e5a7996426f79fd7102025-08-20T03:50:22ZengElsevierMayo Clinic Proceedings: Innovations, Quality & Outcomes2542-45482025-08-019410064210.1016/j.mayocpiqo.2025.100642Immunogenicity and Safety of ChAdOx1 nCoV-19 (AZD1222) as a Homologous Fourth-Dose Booster: A Substudy of the Phase 3 COV003 Trial in BrazilSue Ann Costa Clemens, MD, PhD0Sagida Bibi, PhD1Natalie G. Marchevsky, MSc2Parvinder K. Aley, PhD3Federica Cappuccini, PhD4Sophie A. Davies, BSc5Isabela Gonzalez, PhD6Sarah C. Kelly, MSc7Yama F. Mujadidi, MSc8Eveline Pipolo Milan, MD, PhD9Alexandre V. Schwarzbold, PhD10Eduardo Sprinz, MD, DSc11Merryn Voysey, DPhil12Lily Y. Weckx, MD, PhD13Daniel Wright, DPhil14Himanshu Bansal, MS15Maria A.S. Bergagård, MSc16Abby J. Isaacs, MS17Elizabeth J. Kelly, PhD18Dongmei Lan, MS19Shethah Morgan, PhD20Nirmal Kumar Shankar, BAMS21Kathryn Shoemaker, MS22Tonya L. Villafana, PhD23Teresa Lambe, PhD24Justin A. Green, MD, PhD25Andrew J. Pollard, FMedSci26Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, United Kingdom; Institute for Global Health, University of Siena, Italy; Correspondence: Address to Sue Ann Costa Clemens, MD, PhD, Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford OX3 7LE, United Kingdom.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, United KingdomOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, United KingdomOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, United KingdomOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, United KingdomOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, United KingdomInstitute for Global Health, University of Siena, ItalyOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, United KingdomOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, United KingdomCentro de Estudos e Pesquisas em Moléstias Infec, CePCLIN – Centro de Pesquisas Clínicas de Natal, Natal, Rio Grande do Norte, BrazilClinical Research Unit, Department of Clinical Medicine, Universidade Federal de Santa Maria, BrazilHospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, BrazilOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, United KingdomDepartment of Pediatrics, Universidade Federal de São Paulo, BrazilOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, United KingdomBiometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MDClinical Operations, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, SwedenBiometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MDTranslational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD; Currently at Global Immunology, Vaccines R&D, Sanofi, Swiftwater, PABiometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MDClinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United KingdomPatient Safety, Vaccines & Immune Therapies, BioPharmaceuticals, AstraZeneca, Bangalore, IndiaOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, United KingdomClinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MDOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, United Kingdom; Chinese Academy of Medical Science, Oxford Institute, University of Oxford, United KingdomClinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United KingdomOxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, United KingdomObjective: To address that, despite widespread use of ChAdOx1 nCoV-19 (AZD1222) as a COVID-2019 booster, fourth-dose clinical outcomes data are limited. We report immunogenicity and safety for ChAdOx1 nCoV-19 as a homologous fourth-dose booster. Participants and Methods: Participants (aged ≥18 years) who had received 2 doses of ChAdOx1 nCoV-19 in phase 3 COV003 trial in Brazil were offered a third dose after a planned dose interval from 11 to 13 months and a fourth dose after a planned interval from 6 to 15 months (both 5 × 1010 viral particles). All fourth doses were administered to substudy participants between August 18 and October 28, 2022. The data cutoff was December 9, 2022. The primary immunogenicity outcome was noninferiority of ancestral severe acute respiratory syndrome coronavirus (SARS-CoV)-2–neutralizing antibody responses 28 days after dose 4 versus dose 3. Solicited and unsolicited adverse events were recorded 7 and 28 days postdose 4, respectively. Results: 172 participants received a fourth dose (median interval postthird dose, 10.7 months). Ancestral SARS-CoV-2–neutralizing antibody titers postdose 4 were noninferior to those postdose 3; geometric mean fold rise was 1.9 (95% CI, 1.6-2.4; n=112). Immunogenicity results were consistent across all variants analyzed. Local and systemic solicited adverse events were reported in 60.3% (n=35/58) and 43.1% (n=25/58) of participants, respectively. Conclusion: Immune responses after a fourth dose of ChAdOx1 nCoV-19 were noninferior to those after a third dose across SARS-CoV-2 variants. The fourth dose was well tolerated with no emergent safety concerns, supporting the continued development of the ChAdOx1 platform in preparation for future pandemics. Trial Registration: clinicaltrials.gov Identifier: NCT04536051http://www.sciencedirect.com/science/article/pii/S2542454825000530 |
| spellingShingle | Sue Ann Costa Clemens, MD, PhD Sagida Bibi, PhD Natalie G. Marchevsky, MSc Parvinder K. Aley, PhD Federica Cappuccini, PhD Sophie A. Davies, BSc Isabela Gonzalez, PhD Sarah C. Kelly, MSc Yama F. Mujadidi, MSc Eveline Pipolo Milan, MD, PhD Alexandre V. Schwarzbold, PhD Eduardo Sprinz, MD, DSc Merryn Voysey, DPhil Lily Y. Weckx, MD, PhD Daniel Wright, DPhil Himanshu Bansal, MS Maria A.S. Bergagård, MSc Abby J. Isaacs, MS Elizabeth J. Kelly, PhD Dongmei Lan, MS Shethah Morgan, PhD Nirmal Kumar Shankar, BAMS Kathryn Shoemaker, MS Tonya L. Villafana, PhD Teresa Lambe, PhD Justin A. Green, MD, PhD Andrew J. Pollard, FMedSci Immunogenicity and Safety of ChAdOx1 nCoV-19 (AZD1222) as a Homologous Fourth-Dose Booster: A Substudy of the Phase 3 COV003 Trial in Brazil Mayo Clinic Proceedings: Innovations, Quality & Outcomes |
| title | Immunogenicity and Safety of ChAdOx1 nCoV-19 (AZD1222) as a Homologous Fourth-Dose Booster: A Substudy of the Phase 3 COV003 Trial in Brazil |
| title_full | Immunogenicity and Safety of ChAdOx1 nCoV-19 (AZD1222) as a Homologous Fourth-Dose Booster: A Substudy of the Phase 3 COV003 Trial in Brazil |
| title_fullStr | Immunogenicity and Safety of ChAdOx1 nCoV-19 (AZD1222) as a Homologous Fourth-Dose Booster: A Substudy of the Phase 3 COV003 Trial in Brazil |
| title_full_unstemmed | Immunogenicity and Safety of ChAdOx1 nCoV-19 (AZD1222) as a Homologous Fourth-Dose Booster: A Substudy of the Phase 3 COV003 Trial in Brazil |
| title_short | Immunogenicity and Safety of ChAdOx1 nCoV-19 (AZD1222) as a Homologous Fourth-Dose Booster: A Substudy of the Phase 3 COV003 Trial in Brazil |
| title_sort | immunogenicity and safety of chadox1 ncov 19 azd1222 as a homologous fourth dose booster a substudy of the phase 3 cov003 trial in brazil |
| url | http://www.sciencedirect.com/science/article/pii/S2542454825000530 |
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