Table 1.
Non-inferiority and superiority of PsVN titers against D614G and B.1.351 following monovalent and bivalent boosters compared with MV D614 primary vaccination or compared with pre-booster PsVN titers–PPAS.
| A. Monovalent D614 booster group | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Priming vaccine or vaccine platform subgroup | Booster D15 |
Control D36 |
Post-booster vs control |
Post-booster vs pre-booster |
|||||||
| Strain | M | Strain | M | GMT ratio | 98.3% CI | NIa | M | GMTR | 98.3% CI | Superiorityb | |
| BNT162b2 | D614G | 202 | D614G | 302 | 2.16 | 1.69; 2.75 | Yes | 189 | 23.37 | 18.58; 29.38 | Yes |
| mRNA vaccine platform | D614G | 269 | D614G | 302 | 2.09 | 1.66; 2.64 | Yes | 255 | 18.08 | 14.75; 22.16 | Yes |
| Pooled Ad virus vectored platform | D614G | 131 | D614G | 302 | 1.89 | 1.43; 2.49 | Yes | 108 | 30.18 | 20.56; 44.31 | Yes |
| MV D614 | D614G | 52 | D614G | 302 | 7.27 | 5.34; 9.89 | Yes | 45 | 51.63 | 22.29; 119.57 | Yes |
| B. Monovalent B.1.351 booster group | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Priming vaccine or vaccine platform subgroup | Booster D15 |
Control D36 |
Post-booster vs control |
Post-booster vs pre-booster |
|||||||
| Strain | M | Strain | M | GMT ratio | 98.3% CI | NIa | M | GMTR | 98.3% CI | Superiorityb | |
| BNT162b2 | B.1.351 | 279 | D614G | 302 | 1.96 | 1.54; 2.50 | Yes | 256 | 35.41 | 26.71; 46.95 | Yes |
| B.1.351 | 279 | B.1.351 | 291 | 17.36 | 13.39; 22.50 | Yesc | – | – | – | – | |
| mRNA vaccine platform | B.1.351 | 347 | D614G | 302 | 2.06 | 1.62; 2.61 | Yes | 321 | 34.19 | 26.58; 43.98 | Yes |
| C. Bivalent D614+B.1.351 booster group | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Priming vaccine or vaccine platform subgroup | Booster D15 |
Control D36 |
Post-booster vs control |
Post-booster vs pre-booster |
|||||||
| Strain | M | Strain | M | GMT ratio | 98.3% CI | NIa | M | GMTR | 98.3% CI | Superiorityb | |
| BNT162b2 | D614G | 276 | D614G | 302 | 2.34 | 1.84; 2.96 | Yes | 269 | 14.39 | 11.34; 18.28 | Yes |
| B.1.351 | 276 | D614G | 302 | 1.39 | 1.09; 1.77 | Yes | 248 | 34.18 | 25.84; 45.22 | Yes | |
| B.1.351 | 276 | B.1.351 | 291 | 12.31 | 9.50; 15.97 | Yesc | – | – | – | – | |
| mRNA vaccine platform | D614G | 343 | D614G | 302 | 2.52 | 2.00; 3.16 | Yes | 332 | 13.04 | 10.56; 16.11 | Yes |
| B.1.351 | 342 | D614G | 302 | 1.47 | 1.16; 1.85 | Yes | 309 | 31.19 | 24.33; 39.97 | Yes | |
D, study day; M, number of participants with available data for the analysis; NI, non-inferiority.
The two-sided 98.3% confidence intervals presented were adjusted for multiple testing using Bonferroni method to adjust the Type 1 error at 0.025 (one-sided) over the 3 comparisons (each booster candidate versus the control group).
Non-inferiority of a booster response against D614G or B.1.351 compared to a response against D614G in the control group was concluded if the lower bound of the 98.3% CI for the between-group (booster versus control) GMT ratio was >0.67.
Superiority of a booster response compared to a pre-booster response was concluded if the lower limit of the 2-sided 98.3% CI of the fold-rise (post-booster versus pre-booster) was >2.
Superiority, rather than non-inferiority, was demonstrated for this comparison (conditional secondary objective). The superiority of a booster dose response against B.1.351 of monovalent B.1.351 or bivalent D614+B.1.351 in BNT162b2 primed participants aged 18-55 years compared to a response against B.1.351 in the control group was concluded if the lower limit of the 2-sided 98.3% CI of the ratio of GMTs between groups was > 1.5.