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, randomized 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 or 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 or 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 or 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 or 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 logistic 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 or 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 or 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 logistic 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 or 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 or 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