Table 1. Direct meta-analyses comparing the immunogenicity (rates of seroconversion *) of H1N1 influenza vaccines at higher versus next lower doses of hemagglutinin antigen (HA).
| Adults 1 | Elderly 2 | Adolescents 3 | Children 4 | All ages | |||||
| RR (95%CI) | N (ref.) | RR (95%CI) | N (ref.) | RR (95%CI) | N (ref.) | RR (95%CI) | N (ref.) | RR (95%CI) | |
| Non-adjuvanted vaccines | |||||||||
| 15 vs 7.5 (1 dose only) | 1.05 (1.02–1.09) | 2334 [12], [19], [29], [33] | 1.07 (1.00–1.14) | 1583 [19], [29], [33] | 1.00 (0.97–1.03) | 1309 [19] | 1.07 (1.00–1.15) | 1755 [19], [28] | 1.05 (1.01–1.09) |
| 30 vs 15 (1 dose only) | 1.02 (1.00–1.06) | 3607 [11], [15], [18], [19], [29], [33] | 1.12 (1.04–1.22) | 2447 [11], [17], [19], [29], [33] | 1.02 (1.00–1.03) | 2094 [8], [19] | 1.08 (1.05–1.12) | 2481 [8], [19], [26], [54] | 1.05 (1.03–1.08) |
| All dosages ** (1 dose only) | 1.03 (1.01–1.06) | 4320 | 1.09 (1.04–1.15) | 2890 | 1.01 (1.00–1.03) | 2312 | 1.08 (1.04–1.12) | 3123 | 1.05 (1.03–1.07) |
| 15 vs 7.5 (2 doses) | 0.99 (0.97–1.01) | 1481 [12], [19] | 1.09 (1.02–1.16) | 848 [19] | 1.00 (0.99–1.02) | 1112 [19] | 1.03 (0.98–1.09) | 1559 [19], [28] | 1.02 (0.99–1.04) |
| 30 vs 15 (2 doses) | 1.02 (0.98–1.06) | 2561 [11], [15], [18], [19] | 1.14 (0.88–1.47) | 1588 [11], [18], [19] | 1.00 (1.00–1.01) | 1763 [8], [19] | 1.00 (0.99–1.01) | 2174 [8], [19], [26], [54] | 1.01 (1.00–1.02) |
| All dosages ** (2 doses) | 1.00 (0.98–1.02) | 2917 | 1.11 (0.98–1.25) | 1725 | 1.00 (0.99–1.01) | 1958 | 1.01 (0.99–1.04) | 2762 | 1.01 (1.00–1.03) |
| Adjuvanted vaccines | |||||||||
| 7.5 vs 1.88–5.25 (1 dose only) | 0.96 (0.84–1.08) | 593 [12], [19], [55] | – | 0 | 1.28 (0.91–1.79) | 58 [37] Sq | 1.53 (1.01–2.33) | 58 [37] Sq | 1.02 (0.89–1.17) |
| 0.96 (0.83–1.11) | 307 [19] Al | ||||||||
| 0.93 (0.72–1.19) | 286 [12], [55] Sq | ||||||||
| 15 vs 7.5 (1 dose only) | 1.16 (1.06–1.28) | 486 [12], [19] | 1.31 (1.07–1.59) | 216 [19] Al | 1.12 (1.03–1.22) | 407 [19] Al | 1.29 (1.11–1.50) | 398 [19] Al | 1.18 (1.11–1.26) |
| 1.15 (1.03–1.28) | 410 [19] Al | ||||||||
| 1.25 (0.99–1.57) | 76 [12] Sq | ||||||||
| All dosages ** (1 dose only) | 1.04 (0.96–1.12) | 925 | 1.16 (0.92–1.48) | 324 | 1.10 (1.02–1.17) | 570 | 1.32 (1.14–1.52) | 456 | 1.10 (1.04–1.17) |
| 7.5 vs 1.88–5.25 (2 doses) | 1.02 (0.92–1.12) | 347 [12], [19] | – | 0 | 1.00 (0.94–1.07) | 58 [37] Sq | 1.00 (0.94–1.07) | 58 [37] Sq | 1.00 (0.96–1.05) |
| 1.03 (0.91–1.17) | 298 [19] Al | ||||||||
| 1.00 (0.84–1.18) | 49 [12] Sq | ||||||||
| 15 vs 7.5 (2 doses) | 1.17 (1.08–1.26) | 396 [19] Al | 0.99 (0.88–1.10) | 204 [19] Al | 1.07 (1.00–1.14) | 375 [19] Al | 1.04 (1.00–1.09) | 389 [19] Al | 1.07 (1.01–1.13) |
| All dosages ** (2 doses) | 1.08 (1.02–1.14) | 639 | 1.06 (0.95–1.19) | 308 | 1.04 (1.00–1.09) | 523 | 1.03 (0.98–1.07) | 447 | 1.05 (1.02–1.07) |
Only randomized trials were included. All doses are in µg. N = total number of subject analyzed; (ref) = References to included studies; RR = Random-effect risk ratio; CI = Confidence Intervals.
Adults = from 18 to 64 years;
Elderly = from 65 years;
Adolescents = from 10 to 17 years;
Children = from 6 months to 9 years (see Table S1 for several exceptions).
*Seroconversion = subjects with a pre-vaccination hemagglutinination-inhibition antibody titer < = 1∶10 and a post-vaccination titer > = 1∶40, or a pre-vaccination titer > = 1∶10 and an increase in the titer by a factor of four or more after vaccination.
**The total sample of overall meta-analyses may be lower (higher) than the sum of stratified meta-analyses because some arms had to be split to be included in more than a stratified meta-analysis (some arms were different from the main comparisons shown in the Table). In any case, no patient was included more than once in any of the meta-analyses. Al = Only aluminum adjuvants; Sq = Only squalene-based (oil-in-water) adjuvants.