Munro, Alasdair PS, Feng, Shuo, Janani, Leila, Cornelius, Victoria, Aley, Parvinder K, Babbage, Gavin, Baxter, David, Bula, Marcin, Cathie, Katrina, Chatterjee, Krishna et al (show 45 more authors)
(2022)
Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial.
LANCET INFECTIOUS DISEASES, 22 (8).
pp. 1131-1141.
Abstract
<h4>Background</h4>Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.<h4>Methods</h4>The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 μg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 μg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (anti-spike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.<h4>Findings</h4>Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6-77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3-214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030-27 162), which increased to 37 460 ELU/mL (31 996-43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41-1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996-30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826-64 452), with a geometric mean fold change of 2·19 (1·90-2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37-14·32) and 15·90 (12·92-19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24-16·54] in the BNT162b2 group and 6·22 [3·90-9·92] in the mRNA-1273 group).<h4>Interpretation</h4>Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose.<h4>Funding</h4>UK Vaccine Task Force and National Institute for Health Research.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | 10 center dot 37-14 center dot 32) and 15 center dot 90 (12 center dot 92-19 center dot 58) in the BNT162b2 and mRNA-1273 groups, 166 participants were screened, 2022, 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose., 37 460 ELU/mL (31996-43857) at day 14 after the fourth dose, 46 826-64 452), 50 mu g in 0 center dot 25 mL; half dose) via, 73765130, 95% CI 1 center dot 41-1 center dot 78). There was a significant increase in geometric mean anti-spike protein IgG, 95% CI 20 996-30 528) to 14 days after a fourth dose, a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a, after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030-27 162), also boosted after the fourth dose (eg, and had available endpoint data. This trial is registered with ISRCTN, and immunogenicity (antispike, and is ongoing., and possibly better than, and received either, blinded, BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth, changes in anti-spike protein IgG titres from before (day 0) to after ( day 14) the fourth dose were 12 center dot 19 (95% CI, concentration from 28 days after the third dose (25 317 ELU/mL, dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants, dose of either BNT162b2 (30 mu g in 0 center dot 30 mL; full dose) or mRNA-1273 (Moderna, Findings Between Jan 11 and Jan 25, full-dose BNT162b2 (n=83) or half, geometric mean anti-spike protein IgG concentration at day 28, immunity. Peak responses after the fourth dose were similar to, Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral, interval between the third and fourth doses was 208 center dot 5 days (IQR 203 center dot 3-214 center dot 8). Pain was the most common local, intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study, masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, mean 1 center dot 59, Methods The COV-BOOST trial is a multicentre, modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster, mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were, of mRNA-1273 (54 936 ELU/mL, peak responses after the, phase 2, protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at, randomised controlled trial of seven COVID-19, randomly assigned, related to the study vaccine. In the BNT162b2 group, representing a significant fold change (geometric, respectively. T-cell responses were, Safety and reactogenicity were assessed in the per-protocol population, solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or, statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were, the fold changes for the wild-type variant from before to after the fourth dose, third dose., vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received, was 70 center dot 1 years (IQR 51 center dot 6-77 center dot 5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median, were 7 center dot 32 [95% CI 3 center dot 24-16 center dot 54] in the BNT162b2 group and 6 center dot 22 [3 center dot 90-9 center dot 92] in the mRNA-1273 group)., which comprised all participants who received, which increased to, with a geometric mean fold change of 2 center dot 19 (1 center dot 90-2 center dot 52). The fold |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Clinical Directorate Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 21 Apr 2023 09:12 |
| Last Modified: | 21 Apr 2023 09:12 |
| DOI: | 10.1016/S1473-3099(22)00271-7 |
| Open Access URL: | https://doi.org/10.1016/S1473-3099(22)00271-7 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3169820 |
Dimensions
Dimensions
