tetano
Editor, Senior Moderator
Mayo Clin Proc Innov Qual Outcomes
. 2025 Jul 11;9(4):100642.
doi: 10.1016/j.mayocpiqo.2025.100642. eCollection 2025 Aug. Immunogenicity and Safety of ChAdOx1 nCoV-19 (AZD1222) as a Homologous Fourth-Dose Booster: A Substudy of the Phase 3 COV003 Trial in Brazil
Sue Ann Costa Clemens[SUP] 1 2 [/SUP], Sagida Bibi[SUP] 1 [/SUP], Natalie G Marchevsky[SUP] 1 [/SUP], Parvinder K Aley[SUP] 1 [/SUP], Federica Cappuccini[SUP] 1 [/SUP], Sophie A Davies[SUP] 1 [/SUP], Isabela Gonzalez[SUP] 2 [/SUP], Sarah C Kelly[SUP] 1 [/SUP], Yama F Mujadidi[SUP] 1 [/SUP], Eveline Pipolo Milan[SUP] 3 [/SUP], Alexandre V Schwarzbold[SUP] 4 [/SUP], Eduardo Sprinz[SUP] 5 [/SUP], Merryn Voysey[SUP] 1 [/SUP], Lily Y Weckx[SUP] 6 [/SUP], Daniel Wright[SUP] 1 [/SUP], Himanshu Bansal[SUP] 7 [/SUP], Maria A S Bergagård[SUP] 8 [/SUP], Abby J Isaacs[SUP] 7 [/SUP], Elizabeth J Kelly[SUP] 9 10 [/SUP], Dongmei Lan[SUP] 7 [/SUP], Shethah Morgan[SUP] 11 [/SUP], Nirmal Kumar Shankar[SUP] 12 [/SUP], Kathryn Shoemaker[SUP] 1 [/SUP], Tonya L Villafana[SUP] 13 [/SUP], Teresa Lambe[SUP] 1 14 [/SUP], Justin A Green[SUP] 11 [/SUP], Andrew J Pollard[SUP] 1 [/SUP]
Affiliations
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 × 10[SUP]10[/SUP] 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.
. 2025 Jul 11;9(4):100642.
doi: 10.1016/j.mayocpiqo.2025.100642. eCollection 2025 Aug. Immunogenicity and Safety of ChAdOx1 nCoV-19 (AZD1222) as a Homologous Fourth-Dose Booster: A Substudy of the Phase 3 COV003 Trial in Brazil
Sue Ann Costa Clemens[SUP] 1 2 [/SUP], Sagida Bibi[SUP] 1 [/SUP], Natalie G Marchevsky[SUP] 1 [/SUP], Parvinder K Aley[SUP] 1 [/SUP], Federica Cappuccini[SUP] 1 [/SUP], Sophie A Davies[SUP] 1 [/SUP], Isabela Gonzalez[SUP] 2 [/SUP], Sarah C Kelly[SUP] 1 [/SUP], Yama F Mujadidi[SUP] 1 [/SUP], Eveline Pipolo Milan[SUP] 3 [/SUP], Alexandre V Schwarzbold[SUP] 4 [/SUP], Eduardo Sprinz[SUP] 5 [/SUP], Merryn Voysey[SUP] 1 [/SUP], Lily Y Weckx[SUP] 6 [/SUP], Daniel Wright[SUP] 1 [/SUP], Himanshu Bansal[SUP] 7 [/SUP], Maria A S Bergagård[SUP] 8 [/SUP], Abby J Isaacs[SUP] 7 [/SUP], Elizabeth J Kelly[SUP] 9 10 [/SUP], Dongmei Lan[SUP] 7 [/SUP], Shethah Morgan[SUP] 11 [/SUP], Nirmal Kumar Shankar[SUP] 12 [/SUP], Kathryn Shoemaker[SUP] 1 [/SUP], Tonya L Villafana[SUP] 13 [/SUP], Teresa Lambe[SUP] 1 14 [/SUP], Justin A Green[SUP] 11 [/SUP], Andrew J Pollard[SUP] 1 [/SUP]
Affiliations
- PMID: 40686533
- PMCID: PMC12275839
- DOI: 10.1016/j.mayocpiqo.2025.100642
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 × 10[SUP]10[/SUP] 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.