Potential serotype-specific effectiveness against IPD of pneumococcal conjugate vaccines V114 and PCV20 in children given a 2+1 dosing regimen

Figures & data

Table 1. Summary-level input data and sources.

	Vaccine effectiveness^a	ELISA-normalized geometric mean serotype-specific antibody concentration (µg/mL)
Serotype	PCV13 (95% CI)	Placebo (95% CI)^b	PCV13 (95% CI)^c,d,e	V114 (95% CI)^c	PCV20 (95% CI)^d
4	93% (89-96)^f	0.04 (0.03-0.05)	1.03 (0.98-1.07)	1.22 (1.17-1.28)	0.55 (0.51-0.60)
6B	93% (82-97)	0.09 (0.08-0.09)	0.26 (0.24-0.28)	0.46 (0.42-0.50)	0.12 (0.10-0.13)
9 V	97% (85-100)	0.08 (0.07-0.08)	0.83 (0.80-0.87)	0.86 (0.82-0.89)	0.47 (0.43-0.52)
14	97% (93-99)	0.17 (0.15-0.19)	2.88 (2.69-3.08)	3.95 (3.68-4.23)	1.07 (0.97-1.19)
18C	93% (89-96)^f	0.06 (0.06-0.07)	0.91 (0.87-0.96)	0.85 (0.81-0.88)	0.60 (0.55-0.66)
19F	84% (69-92)	0.24 (0.23-0.25)	3.20 (3.07-3.33)	2.73 (2.62-2.85)	1.98 (1.83-2.14)
23F	93% (89-96)^f	0.10 (0.10-0.11)	0.47 (0.45-0.50)	0.77 (0.73-0.83)	0.17 (0.16-0.19)
1	85% (68-93)	0.05 (0.04-0.05)	1.25 (1.20-1.30)	1.16 (1.11-1.21)	0.62 (0.57-0.68)
3	65% (44-78)	0.07 (0.07-0.08)	0.51 (0.49-0.53)	0.85 (0.82-0.88)	0.38 (0.35-0.41)
5	79% (71-85)^f	0.09 (0.08-0.10)	0.73 (0.70-0.76)	0.65 (0.61-0.68)	0.49 (0.44-0.53)
6A	93% (82-97)	0.13 (0.13-0.14)	1.12 (1.07-1.18)	0.72 (0.68-0.76)	0.50 (0.46-0.53)
7F	91% (82-96)	0.07 (0.06-0.07)	1.65 (1.58-1.71)	1.53 (1.46-1.60)	0.95 (0.88-1.01)
19A	83% (74-89)	0.33 (0.31-0.34)	1.68 (1.61-1.76)	1.48 (1.42-1.55)	0.95 (0.89-1.03)

CI, confidence interval; PCV13, 13-valent pneumococcal conjugate vaccine; PCV20, 20-valent pneumococcal conjugate vaccine; V114, 15-valent pneumococcal conjugate vaccine.

^aSource: Savulescu et al. [2].

^bSource: Clinical trial NCT01340937 [18].

^cSource: Clinical trials PNEU-PED-EU-1 (NCT04031846) [20] and PNEU-PED-EU-2 (NCT04016714) [21].

^dSource: Clinical trial NCT04546425 [22].

^eTrial arms for PCV13 were pooled.

^fIn Savulescu et al., effectiveness estimates were not available for serotypes 4, 18C, 23F, and 5, so the overall estimate for ‘PCV7’ was used for serotypes 4, 18C, and 23F, and the estimate for ‘PCV13non7’ was used for serotype 5 (quotes indicate the labels in the original publication).

Table 2. Estimated protective antibody concentrations.

Serotype	Protective antibody concentration (median (95% CI) µg/mL)
4	0.27 (0.19-0.36)
6B^a	NA
9 V	0.09 (0.03-0.35)
14	0.09 (0.05-0.22)
18C	0.16 (0.10-0.24)
19F	1.49 (0.95-2.39)
23F	0.03 (0.01-0.06)
1	0.55 (0.33-0.87)
3	0.36 (0.28-0.54)
5	0.32 (0.26-0.42)
6A	0.19 (0.04-0.47)
7F	0.57 (0.39-0.84)
19A	0.73 (0.12-1.02)

CI, confidence interval.

^aC_p for serotype 6B could not be calculated, as described in Methods and Discussion sections.

Table 3. Observed PCV13 effectiveness versus effectiveness predicted for V114 and PCV20.

		V114		PCV20
Serotype	Observed PCV13 effectiveness, median % (95% CI)^a	Predicted effectiveness, median % (95% CI)	Difference, percentage points^b	Predicted effectiveness, median % (95% CI)	Difference, percentage points^b
4	93% (89-96)^d	97% (93-98)	+4	70% (62-79)	−23
6B^c	93% (82-97)	NA	NA	NA	NA
9 V	97% (85-100)	98% (88-100)	+1	85% (59-95)	−12
14	97% (93-99)	99% (95-100)	+2	91% (81-97)	−6
18C	93% (89-96)^d	97% (93-99)	+4	85% (76-91)	−8
19F	84% (69-92)	81% (58-93)	−3	61% (45-75)	−23
23F	93% (89-96)^d	100% (94-100)	+7	0% (0-15)	−93
1	85% (68-93)	88% (68-96)	+3	52% (37-69)	−33
3	65% (44-78)	93% (78-97)	+28	47% (36-55)	−18
5	79% (71-85)^d	79% (68-85)	0	60% (52-67)	−19
6A	93% (82-97)	88% (70-100)	−5	64% (46-72)	−29
7F	91% (82-96)	91% (81-96)	0	73% (58-84)	−18
19A	83% (74-89)	84% (71-100)	+1	59% (30-68)	−24

CI, confidence interval; PCV13, 13-valent pneumococcal conjugate vaccine; PCV20, 20-valent pneumococcal conjugate vaccine; V114, 15-valent pneumococcal conjugate vaccine.

^aSource: Savulescu et al. [2].

^bDifferences are predicted VE minus observed VE.

^cVE for serotype 6B could not be calculated, as described in Methods and Discussion sections.

^dIn Savulescu et al., effectiveness estimates were not available for serotypes 4, 18C, 23F, and 5, so the overall estimate for ‘PCV7’ was used for serotypes 4, 18C, and 23F, and the estimate for ‘PCV13non7’ was used for serotype 5 (quotes indicate the labels in the original publication).

Figure 1. Absolute difference in predicted vaccine effectiveness for V114 and PCV20.

PCV20, 20-valent pneumococcal conjugate vaccine; V114, 15-valent pneumococcal conjugate vaccine.

The solid points are the median values, over 5,000 simulations, of the predicted VEs (%) for V114 minus the (respective) VEs for PCV20. Values greater than zero favor V114. The red dashed line indicates the median difference (20.9). The whiskers are 95% CIs calculated using the empirical 2.5%ile and 97.5%iles of the differences.

*The predicted difference for serotype 23F is partly due to relatively low values and high variability of PCV20 titers, as explained further in the manuscript the VE was bounded at 0. CIs were bounded at 100%.

Savulescu C, Krizova P, Valentiner-Branth P, et al. Effectiveness of 10 and 13-valent pneumococcal conjugate vaccines against invasive pneumococcal disease in European children: spidnet observational multicentre study. Vaccine. 2022 Jun 23;40(29):3963–3974. doi: 10.1016/j.vaccine.2022.05.011

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Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article or its supplementary materials.