Safety and immunogenicity of 13-valent pneumococcal conjugate vaccine formulations with and without aluminum phosphate and comparison of the formulation of choice with 23-valent pneumococcal polysaccharide vaccine in elderly adults

Figures & data

Figure 1. CONSORT diagram showing disposition of study participants. Abbreviations: PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.

Table 1. Participant demographics of the evaluable immunogenicity population

	Parent trial					Extension trial
Characteristic	Year 0			Year 1		Year 2
	PCV13^a (n = 299)	PCV13−AlPO4^b (n = 295)	PPSV23 (n = 295)	PCV13/PCV13 (n = 131)	PCV13/PPSV23 (n = 126)	PCV13/PPSV23/PCV13 (n = 98)
Sex %
Female	57.9	55.9	60.0	60.3	54.0	53.1
Male	42.1	44.1	40.0	39.7	46.0	46.9
Ethnic origin, %
White	62.2	63.1	63.4	58.8	60.3	55.1
Other^c	37.8	36.9	36.6	41.2	39.7	44.9
Mean age, y (SD)	70.7 (4.8)	70.7 (4.9)	70.7 (4.9)	71.3 (4.8)	71.8 (4.9)	72.8 (4.8)

^a PCV13 formulation containing AlPO₄. ^bPCV13 formulation without AlPO₄. ^cThe majority under Other were of mixed race background; there were also single individuals of Asian or Black race.

Abbreviations: AlPO₄, aluminum phosphate; PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine; SD, standard deviation.

Table 2. Pneumococcal IgG GMCs 1 mo after PCV13 without or with AlPO₄ (evaluable immunogenicity population)

	PCV13−AlPO4^a	PCV13 (with AlPO4)	PCV13−AlPO4^a relative to PCV13 (with AlPO4) GMC ratio (95% CI)^c
Serotype	IgG GMC^b (μg/mL) n = 298^d	IgG GMC^b (μg/mL) n = 300^d
1	6.8	6.8	1.0 (0.8–1.3)
3	2.3	2.5	0.9 (0.7–1.1)
4	4.8	4.9	1.0 (0.8–1.3)
5	18.6	18.2	1.0 (0.8–1.3)
6A	9.2	8.7	1.1 (0.8–1.3)
6B	12.7	14.6	0.9 (0.7–1.1)
7F	11.0	7.4	1.5 (1.2–1.8)
9V	12.5	11.9	1.1 (0.8–1.3)
14	23.6	18.7	1.3 (1.0–1.7)
18C	23.7	22.1	1.1 (0.9–1.3)
19A	27.0	27.9	1.0 (0.8–1.2)
19F	11.6	12.0	1.0 (0.7–1.3)
23F	8.8	10.8	0.8 (0.6–1.1)

^a PCV13 formulation without AlPO₄. ^bGMCs were calculated using all participants with available data. ^cRatio of GMCs (PCV13 without AlPO₄ to PCV13 with AlPO₄). ^dNumber of participants randomized to the vaccine group; all participants had valid and determinate assay results for the given serotypes. Abbreviations: AlPO₄, aluminum phosphate; CI, confidence interval; GMC, geometric mean concentration; IgG, immunoglobulin G; PCV13, 13-valent pneumococcal conjugate vaccine.

Table 3. Pneumococcal immune responses 1 mo after PCV13 and PPSV23 (evaluable immunogenicity population)

Serotype	OPA GMT^a		PCV13 relative to PPSV23 GMT ratio (95% CI)	IgG GMC^a		PCV13 relative to PPSV23 GMC ratio (95% CI)
	PCV13 n^b = 261–293	PPSV23 n^b = 271–286		PCV13 (n^b = 299)	PPSV23 (n^b = 295)
	GMT	GMT		GMC	GMC
1	173.17	77.91	2.22 (1.65–2.99)	6.92	3.62	1.91 (1.48–2.46)
3	141.58	74.07	1.91 (1.52–2.41)	2.57	1.74	1.48 (1.23–1.78)
4	2429.40	1402.22	1.73 (1.33–2.26)	4.83	2.77	1.74 (1.36–2.24)
5	485.09	149.75	3.24 (2.30–4.56)	18.33	8.75	2.10 (1.64–2.67)
6A^c	4324.45	605.32	7.14 (5.00–10.20)	8.69	4.03	2.16 (1.75–2.66)
6B	3175.10	1130.44	2.81 (2.02–3.91)	14.51	6.56	2.21 (1.71–2.86)
7F	797.44	1235.06	0.65 (0.46–0.90)	7.46	8.46	0.88 (0.73–1.07)
9V	971.53	289.23	3.36 (2.22–5.09)	12.15	5.63	2.16 (1.72–2.70)
14	821.41	933.29	0.88 (0.63–1.23)	18.70	16.30	1.15 (0.87–1.52)
18C	2770.19	1107.39	2.50 (1.83–3.41)	22.10	8.80	2.51 (2.01–3.14)
19A	1123.60	648.55	1.73 (1.35–2.23)	28.08	13.28	2.11 (1.68–2.66)
19F	870.68	413.19	2.11 (1.48–2.99)	12.22	5.91	2.07 (1.61–2.66)
23F	585.75	198.69	2.95 (2.02–4.31)	10.85	4.94	2.20 (1.69–2.85)

^a GMTs and GMCs were calculated using available data from eligible participants for the specified blood draw. ^bNumber of participants with determinate antibody titer to the given serotype. ^cSerotype 6A is present in PCV13 but not in PPSV23. Abbreviations: CI, confidence interval; GMC, geometric mean concentrations; GMT, geometric mean titers; IgG, immunoglobulin G; OPA, opsonophagocytic activity; PCV13, 13-valent pneumococcal conjugate vaccine (with aluminum phosphate); PPSV23, 23-valent pneumococcal polysaccharide vaccine.

Table 4. Immune responses 1 mo after vaccine sequence PCV13/PPSV23 given at a 1-y interval compared with after a single dose of PPSV23 (evaluable immunogenicity population)

	PCV13/PPSV23	PPSV23	PCV13/PPSV23 relative to PPSV23
Serotype	OPA GMT^a n^b = 118–126	OPA GMT^a n^b = 271–286	GMT ratios (95% CI)
1	157.69	77.91	2.02 (1.40–2.93)
3	131.23	74.07	1.77 (1.32–2.37)
4	1355.86	1402.22	0.97 (0.68–1.38)
5	310.10	149.75	2.07 (1.34–3.21)
6A^c	1742.87	605.32	2.88 (1.78–4.66)
6B	1840.62	1130.44	1.63 (1.08–2.45)
7F	1098.40	1235.06	0.89 (0.59–1.33)
9V	524.72	289.23	1.81 (1.01–3.26)
14	756.71	933.29	0.81 (0.54–1.21)
18C	1569.79	1107.39	1.42 (0.94–2.15)
19A	786.43	648.55	1.21 (0.90–1.64)
19F	853.01	413.19	2.06 (1.37–3.12)
23F	451.41	198.69	2.27 (1.42–3.63)

^a GMTs were calculated using available data from all eligible participants for specified vaccine group and given vaccination. ^bNumber of participants with assay results for the specified vaccine group and given vaccination. ^cSerotype 6A is present in PCV13, but not in PPSV23. Abbreviations: CI, confidence interval; GMT, geometric mean titers; OPA, opsonophagocytic activity; PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.

Table 5. Immune responses 1 mo after dose 1 and dose 2 of PCV13 (evaluable immunogenicity population)

	PCV13/PCV13	PCV13	Dose 2 vs Dose 1
Serotype	OPA GMT^a n^b = 113–126	OPA GMT^a n^b = 113–126	GMT ratio (95% CI)
1	135	192	0.7 (0.54–0.92)
3	87	145	0.6 (0.51–0.71)
4	1411	2904	0.5 (0.41–0.58)
5	218	500	0.4 (0.35–0.55)
6A	2802	3378	0.8 (0.60–1.15)
6B	2843	3031	0.9 (0.76–1.16)
7F	691	821	0.8 (0.61–1.15)
9V	543	1038	0.5 (0.35–0.78)
14	469	838	0.6 (0.43–0.73)
18C	1547	3000	0.5 (0.42–0.63)
19A	631	995	0.6 (0.54–0.75)
19F	612	650	0.9 (0.70–1.27)
23F	834	607	1.4 (1.02–1.85)

^a GMTs were calculated using available data from all eligible participants with the specified blood draw. ^bNumber of participants with determinate antibody titers to the given serotype at both the postvaccination 1 and postvaccination 2 blood draws. Abbreviations: CI, confidence interval; GMT, geometric mean titers; OPA, opsonophagocytic activity; PCV13, 13-valent pneumococcal conjugate vaccine.

Table 6. Immune responses after each vaccination in the vaccine sequence PCV13/PPSV23/PCV13

Extension trial
	PCV13/PPSV23/PCV13 vs. PCV13 Vaccination 3 vs. Vaccination 1			PCV13/PPSV23/PCV13 vs. PCV13/PPSV23 Vaccination 3 vs. Vaccination 2
	PCV13/PPSV23/PCV13 n = 78−96^a	PCV13 n = 78−96^a		PCV13/PPSV23/PCV13 n = 86−97^a	PCV13/ PPSV23 n = 86−97^a
Serotype	OPA GMT^b	OPA GMT^b	GMT ratio (95% CI)	OPA GMT ^b	OPA GMT^b	GMT ratio (95% CI)
1	78	198	0.4 (0.28–0.56)	81	184	0.4 (0.34–0.57)
3	104	126	0.8 (0.67–1.01)	104	131	0.8 (0.66–0.95)
4	1254	2210	0.6 (0.44–0.72)	1406	1457	1.0 (0.76–1.22)
5	170	413	0.4 (0.32–0.53)	219	326	0.7 (0.57–0.80)
6A	3158	4931	0.6 (0.45–0.91)	3443	1732	2.0 (1.39–2.84)
6B	2440	3251	0.8 (0.56–1.01)	2505	1862	1.3 (1.11–1.63)
7F	353	869	0.4 (0.25–0.65)	351	1292	0.3 (0.18–0.41)
9V	247	977	0.3 (0.16–0.40)	267	624	0.4 (0.27–0.68)
14	550	982	0.6 (0.40–0.78)	557	808	0.7 (0.57–0.83)
18C	1457	2860	0.5 (0.40–0.65)	1452	1753	0.8 (0.66–1.03)
19A	431	1141	0.4 (0.30–0.48)	511	756	0.7 (0.58–0.78)
19F	494	1014	0.5 (0.35–0.67)	527	901	0.6 (0.47–0.73)
23F	661	523	1.3 (0.86–1.86)	731	484	1.5 (1.18–1.94)

^a Number of eligible participants with determinate OPA titer for the specified serotype. ^bGMTs calculated using available data from all eligible participants for the specified blood draw. Abbreviations: CI, confidence interval; GMT, geometric mean titer; OPA, opsonophagocytic activity; PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.

Figure 2. Local reactions reported within 14 d after vaccination. ^aSeverity of redness and swelling: absent (no or minimal redness/swelling present, 0 to <2.5 cm; 0 to <5 caliper units), mild (2.5–5.0 cm; ≥5 to ≤10 caliper units), moderate (5.1–10.0 cm; >10 to ≤20 caliper units), or severe (>10.0 cm; >20 caliper units). ^bSeverity of pain at the injection(s) site: mild (awareness of sign/symptom but easily tolerated), moderate (enough discomfort to interfere with usual activity), or severe (inability to do usual activity).^cSeverity of limitation of arm movement: absent (no limitation), mild (some limitation), moderate (able to move arm above shoulder-level but not above head), or severe (unable to move arm above shoulder). Abbreviations: PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.

Table 7. Systemic events reported within 14 d after vaccination

	Vaccination 1			Vaccination 2		Vaccination 3
Event, %	PCV13−AlPO4 n = 238–278^a	PCV13 (with AlPO4) n = 234–271^a	PPSV23 n = 235–264^a	PCV13/PCV13 n = 95–116^a	PCV13/PPSV23 n = 95–114^a	PCV13/PPSV23/PCV13 n = 78–91^a
Fever^b
Any ≥38 °C	8.8	8.3	9.6	4.1	13.0	7.4
≥38 °C to <38.5 °C	4.9	5.0	4.7	1.0	8.1	3.8
≥38.5 °C to <39 °C	2.5	1.7	1.7	1.0	1.1	2.6
≥39 °C but ≤40 °C	3.3	2.9	3.4	2.1	4.2	2.5
>40 °C	0.4	0	0.4	0	0	1.3
Fatigue	36.5	28.1	34.8	33.6	32.7	27.7
Headache	32.0	30.6	30.7	23.3	23.8	19.8
Chills	6.2	5.9	7.1	3.1	4.2	8.9
Rash	6.3	16.0	10.0	7.2	12.2	2.6
Vomiting	2.5	4.3	4.2	3.2	2.1	1.3
Decreased appetite	15.3	13.5	12.7	7.3	16.2	18.3
New generalized muscle pain	27.8	24.6	25.1	19.4	34.6	21.4
Aggravated generalized muscle pain	11.7	13.0	16.0	14.0	15.0	12.5
New joint pain	16.0	10.7	13.0	11.2	11.5	7.7
Aggravated joint pain	10.6	9.2	10.4	6.3	9.4	6.3
Any systemic event	57.2	60.5	57.2	50.0	54.4	50.5

^a Number of participants with known values. ^bParticipants may be counted in ≥1 category of fever; each category is considered separately. Abbreviations: AlPO₄, aluminum phosphate; PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.