Predicting the impact of new pneumococcal conjugate vaccines: serotype composition is not enough

Figures & data

Figure 1. The formulations of the available pneumococcal conjugate vaccines.

Figure 2. Number of average adjusted cases of pediatric invasive pneumococcal disease ‘covered’ by different pneumococcal conjugate vaccines in the UK based solely on post-PCV7-CRM serotype information (Method A), solely on pre-PCV7-CRM serotype information (Method B) or on a summation (see text for details) of pre- and post-PCV7-CRM data (Method C). (Note: all calculations assume 6A coverage for PCV7-CRM and PHiD-CV-10 due to 6A/6B cross-protection).

Figure 3. Serotype-specific antibody concentrations after administration of different serotype 3-containing pneumococcal conjugated vaccine formulations according to 3 + 1 infant schedules, as measured by ELISA. (A) PCV11-PD, Czech Republic and Slovakia; (B) PCV13-CRM, Germany; (C) PCV11-TT-DT, The Philippines; (D) PCV8-DT, Finland and (E) PCV8-TT, Finland.

Table 1. Efficacy of vaccination with four pneumococcal conjugate vaccine or vaccine candidates in infants and young children against vaccine type and serogroup 6 acute otitis media as assessed in tympanocentesis-based double-blind randomized controlled studies.

Vaccine and study site	All vaccine type cases^†		VT VE (95% CI)	6B cases		6B VE (95% CI)	6A^§ cases		6A^§ VE (95% CI)	Ref.
	Ctl	PCV		Ctl	PCV		Ctl	PCV
PCV7-CRM Finland	250	107	57 (44;67)	56	9	84 (62; 93)	45	19	57 (24;76)	[14]
PCV7-OMP Finland	250	110	56 (44;66)	56	12	79 (58; 89)	45	53	-17 (−85; 26)	[44]
PCV11-PD Czech/Slovak	141	60	58 (41;69)^‡	24	3	88 (58; 96)	11	4	64 (−14; 88)	[33]
PHiD-CV-10 Panama	18	6	67 (17;87)	4	0	100 (n.c.)	3	1	67 (n.c.)	[43]

Per-protocol analyses.

^†Definition of ‘all vaccine type’ will differ by vaccine formulation.

^‡VE of PCV11-PD without serotype 3: ∼68%, calculated from [33].

^§6A included 6A/6C.

CRM: Non-toxic cross-reacting mutant of diphtheria toxin; Ctl: Control group; n.c.: Not calculated; PCV: Protein conjugate vaccine; VE: Vaccine efficacy; VT: Vaccine serotypes.

Table 2. Lack of obvious relationship between serotype-specific immunogenicity and efficacy against vaccine type acute otitis media.

Serotype	PCV7-CRM		PCV7-OMP		Comments
	VE (95% CI)	GMC post-dose 3 (μg/ml)	VE (95% CI)	GMC post-dose 3 (μg/ml)
19F	25 (−14 to 51)	3.3	37 (1 to 59)	3.2	Different point estimates despite similar antibody
4	49 (−175 to 91)	1.7	75 (−122 to 97)	3.5
9V	54 (−48 to 86)	2.5	82 (12 to 96)	1.8	Higher point estimate with one-fourth less antibody
18C	58 (−4 to 83)	3.6	53 (−28 to 83)	1.0	Similar point estimates despite threefold difference in antibody levels
23F	59 (35 to 75)	2.5	52 (28 to 68)	0.7
14	69 (20 to 88)	6.3	58 (10 to 80)	3.2
6B	84 (62 to 93)	2.0	79 (58 to 89)	0.4	Similar point estimates despite fivefold difference in antibody levels

Results with PCV7-CRM [14] and PCV7-OMP [44] as assessed in the Finnish tympanocentesis-based double-blind randomized controlled study (per-protocol analysis).

CRM: Non-toxic cross-reacting mutant of diphtheria toxin; GMC: Geometric mean concentrations; PCV: Protein conjugate vaccine.

Figure 4. Prince Valdemar of Denmark.

Table 3. Trend in 19A cases: comparison pre- versus post-PHiD-CV-10 implementation in vaccine-eligible children (countries reporting at least 5 cases of 19A annually pre-PHiD-CV-10).

Region and schedule	Surveillance period		Vaccine eligible			Ref.
	Before vaccine introduction	1–2 years after vaccine introduction	Age	Annual number of cases 19A
				Pre	Post
Quebec 2 + 1	2008–2009	2010	6–11 m	12	2	[20]
Finland 2 + 1	2003–2008	2010–2013	3–38 m	6.3	1.5	[73]
Netherlands^† 3 + 1	2010	2012	<5 y	9	1	[111]
Brazil 3 + 1	2008–2009	2011	≤2 y	8.5	6	[71]
New Zealand 3 + 1	10/2011–9/2012	2013	<2 y	15	7	[74]
Chile 3 + 1	2007–2010	2012	<2 y	13.5	8	[64]

^†Cerebrospinal fluid or blood only.

m: Months; y: Years.

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