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

SARS-CoV-2 anti-spike protein IgG concentration, ELU/mL Day 28 after the third dose 23 325 (20 030–27 162); 66 25 317 (20 996–30 528); 66 20 502 (16 473–25 517); 35 21 980 (16 476–29 324); 33 26 982 (22 056–33 008); 31 29 161 (23 093–36 823); 33 Day 0 of fourth dose 3049 (2550–3646); 66 3469 (2730–4407); 66 2532 (1974–3247); 35 2571 (1874–3527); 34 3761 (2959–4780); 31 4769 (3421–6648); 32 Day 14 after the fourth dose 37 460 (31 996–43 857); 65 54 936 (46 826–64 452); 67 33 316 (26 942–41 198); 35 52 080 (41 163–65 894); 34 42 949 (34 148–54 019); 30 58 043 (46 693–72 150); 33 Fold change (day 14 after fourth dose vs day 28 after third dose) 1·59 (1·41–1·78); 65 2·19 (1·90–2·52); 66 1·62 (1·35–1·95); 35 2·41 (1·90–3·05); 33 1·54 (1·35–1·76); 30 1·99 (1·71–2·31); 33 Fold change (day 14 after fourth dose vs day 0 of fourth dose) 12·19 (10·37–14·32); 65 15·90 (12·92–19·58); 66 13·16 (10·24–16·91); 35 20·26 (15·09–27·21); 34 11·14 (9·21–13·47); 30 12·30 (9·39–16·11); 32 Cellular response (wild-type), spot forming cells per 10⁶ PBMCs

Day 28 after the third dose 96·03 (65·68–140·42; 35 111·19 (75·87–162·95); 33 133·33 (81·31–218·62); 19 113·40 (57·93–221·98); 17 65·04 (37·76–112·03); 16 108·90 (75·81–156·43); 16 Day 0 of fourth dose 19·32 (10·99–33·97);36 35·32 (20·66–60·40); 34 18·85 (8·31–42·77); 20 42·13 (18·58–95·51); 16 19·93 (9·14–43·48); 16 30·20 (14·71–62·02); 18 Day 14 after the fourth dose 112·64 (80·61–157·38); 20 236·95 (146·04–384·48); 20 141·99 (92·57–217·80); 11 232·98 (116·70–465·12); 11 84·87 (51·94–138·66); 9 241·91 (118·79–492·64); 9 Fold change (day 14 after fourth dose vs day 28 after third dose) 1·10 (0·72–1·70); 18 1·69 (1·22–2·34); 19 1·09 (0·63–1·89); 10 1·16 (0·79–1·70); 11 1·12 (0·54–2·31); 8 2·83 (2·02–3·96); 8 Fold change (day 14 after fourth dose vs day 0 of fourth dose) 7·32 (3·24–16·54); 19 6·22 (3·90–9·92); 20 11·07 (4·21–29·12); 11 6·34 (2·89–13·92); 11 4·14 (1·04–16·54); 8 6·08 (3·86–9·56); 9 Cellular response (beta), spot forming cells per 10⁶ PBMCs

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Due to logistical reasons, only 50% of study sites collected cellular immunology samples (proximity to external laboratory) in the main COV-BOOST study; the cellular immunology samples after the fourth dose were collected in the immunology cohort.

Day 28 after the third dose 98·34 (72·11–134·10); 35 108·85 (76·90–154·07); 33 132·70 (87·79–200·59); 19 120·52 (65·57–221·54); 17 68·89 (45·39–104·57); 16 97·69 (70·62–135·12); 16 Day 0 of fourth dose 18·53 (10·60–32·37); 36 28·35 (15·40–52·19); 34 16·71 (7·50–37·22); 20 37·69 (16·24–87·46); 16 21·07 (9·64–46·06); n=16 22·01 (9·11–53·20); 18 Day 14 after the fourth dose 85·55 (54·11–135·28); 20 245·84 (158·84–380·50); 20 96·25 (55·85–165·86); 11 256·42 (142·42–461·65); 11 74·08 (33·34–164·60); 9 233·50 (117·10–465·64); 9 Fold change (day 14 after fourth dose vs day 28 after third dose) 0·98 (0·64–1·50); 18 1·96 (1·36–2·82); 19 0·93 (0·54–1·61); 10 1·30 (0·91–1·87); 11 1·03 (0·50–2·12); 8 3·45 (2·10–5·69); 8 Fold change (day 14 after fourth dose vs day 0 of fourth dose) 5·47 (2·30–13·02); 19 8·48 (4·72–15·22); 20 7·63 (2·51–23·17); 11 8·98 (4·19–19·23); 11 3·46 (0·85–14·08); 8 7·91 (3·04–20·56); 9 Cellular response (delta), spot forming cells per 10⁶ PBMCs

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Due to logistical reasons, only 50% of study sites collected cellular immunology samples (proximity to external laboratory) in the main COV-BOOST study; the cellular immunology samples after the fourth dose were collected in the immunology cohort.

Day 28 after the third dose 92·48 (66·90–127·85); 35 104·34 (72·95–149·24); 33 130·31 (92·00–184·58); 19 114·49 (61·51–213·11); 17 61·55 (36·64–103·38); 16 94·54 (66·74–133·91); 16 Day 0 of fourth dose 16·40 (9·38–28·68); 36 35·93 (20·29–63·62); 34 18·39 (8·68–38·95); 20 41·93 (17·99–97·78); 16 14·22 (6·02–33·58); 16 31·31 (14·19–69·08); 18 Day 14 after the fourth dose 94·20 (66·92–132·60); 20 239·62 (155·19–369·97); 20 108·24 (69·20–169·28); 11 244·67 (141·79–422·20); 11 79·49 (46·55–135·72); 9 233·59 (111·99–487·24); 9 Fold change (day 14 after fourth dose vs day 28 after third dose) 1·00 (0·68–1·49); 18 2·03 (1·39–2·97); 19 0·88 (0·56–1·38); 10 1·28 (0·89–1·84); 11 1·19 (0·59–2·40); 8 3·85 (2·39–6·21); 8 Fold change (day 14 after fourth dose vs day 0 of fourth dose) 7·57 (3·32–17·25); 19 6·35 (3·51–11·49); 20 9·37 (3·56–24·67); 11 6·62 (2·87–15·25); 11 5·64 (1·27–25·06); 8 6·04 (2·48–14·68); 9