Persistence of antibodies 1 year after sequential administration of the 13-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine in adults

Figures & data

Table 1. Baseline characteristics.

	Study 1 PPSV23-naive adults			Study 2 PPSV23-preimmunized adults
	Vaccine sequence			Vaccine sequence
Characteristic	PCV13/PCV13 (n = 130)	PCV13/PPSV23 (n = 210)	PPSV23/PCV13 (n = 179)	PCV13/PCV13 (n = 221)	PPSV23/PCV13 (n = 222)
Female, %	58.5	59.5	57.0	51.6	51.8
Race, %
White	94.6	95.7	96.1	96.4	94.6
Black or African American	3.8	3.3	3.4	2.3	2.3
Asian	0.8	0	0	0.9	3.2
American Indian or Alaska Native	0.8	0.5	0	0	0
Other	0	0.5	0.6	0	0
Native Hawaiian or other Pacific Islander	0	0	0	0.5	0
Mean (SD) age 1 year after vaccination 2, y	64.0 (1.4)	64.1 (1.4)	64.2 (1.4)	78.3 (4.5)	77.8 (4.1)

Abbreviations: PCV13 = 13-valent pneumococcal conjugate vaccine; PPSV23 = 23-valent pneumococcal polysaccharide vaccine.

Table 2. OPA GMTs among the 3 vaccine sequences 1 year after the second vaccination.

	Vaccine sequence
	GMT^a (95% CI)^b
	Study 1 PPSV23-naive adults			Study 2 PPSV23-preimmunized adults
Serotype	PCV13/PCV13 (n = 122−129)^c	PCV13/PPSV23 (n = 195−209)^c	PPSV23/PCV13 (n = 166−179)^c	PCV13/PCV13 (n = 210−220)^c	PPSV23/PCV13 (n = 208−222)^c
1	54	52	36	38	22
	(40.8, 71.0)	(40.9, 65.5)	(27.1, 46.7)	(30.9, 47.9)	(17.5, 27.8)
3	19	27	18	20	16
	(15.0, 23.5)	(22.2, 32.3)	(14.4, 21.9)	(16.5, 23.4)	(13.3, 19.2)
4	328	355	183	265	172
	(229.0, 469.0)	(264.7, 475.9)	(127.7, 263.2)	(200.8, 348.5)	(129.0, 230.1)
5	29	76	44	58	42
	(20.4, 41.4)	(58.0, 99.7)	(32.9, 59.6)	(45.1, 74.1)	(32.2, 55.6)
6A	316	225	102	250	115
	(216.5, 461.2)	(163.6, 308.3)	(71.4, 146.9)	(187.3, 334.0)	(84.5, 156.8)
6B	785	593	324	510	381
	(540.6, 1140.2)	(441.4, 797.3)	(225.0, 466.1)	(378.2, 686.4)	(281.9, 513.9)
7F	247	412	145	173	115
	(160.4, 380.9)	(313.1, 541.2)	(100.3, 210.7)	(126.0, 237.5)	(81.6, 160.9)
9V	211	221	129	81	68
	(134.3, 330.9)	(154.2, 316.0)	(84.5, 196.5)	(55.1, 117.9)	(47.4, 98.5)
14	379	416	383	202	240
	(273.6, 526.2)	(316.2, 548.2)	(286.9, 510.6)	(154.6, 265.0)	(181.0, 317.0)
18C	393	527	337	540	360
	(271.3, 569.3)	(401.7, 690.5)	(240.7, 471.7)	(435.5, 668.5)	(273.6, 474.5)
19A	244	313	170	232	181
	(189.1, 314.1)	(263.1, 372.3)	(134.4, 214.8)	(193.2, 278.1)	(146.7, 222.9)
19F	256	426	195	277	158
	(182.4, 359.0)	(343.7, 527.7)	(145.1, 262.1)	(218.6, 351.7)	(119.3, 209.9)
23F	110	64	35	103	45
	(73.9, 165.0)	(47.6, 86.5)	(25.6, 48.6)	(78.0, 135.5)	(33.5, 59.6)

Abbreviations: GMT = geometric mean titer; OPA = opsonophagocytic activity; PCV13 = 13-valent pneumococcal conjugate vaccine; PPSV23 = 23-valent pneumococcal polysaccharide vaccine.

^aGMTs are calculated using all subjects with available data for the specific blood draw.

^bCIs for the ratio are back transformations of a CI based on the Student t distribution for the mean logarithm of the titers.

^cn = Number of subjects with a valid and determinate OPA antibody titer for the specified serotype.

Table 3. Comparison of OPA GMTs 1 year after vaccination 2 in PPSV23-naive and PPSV23-preimmunized subjects.

Vaccine sequence
GMT ratio^a (95% CI)^b
	Study 1 PPSV23-naive adults			Study 2 PPSV23-preimmunized adults
Serotype	PCV13/PPSV23 (n = 195–209)^c vs PPSV23/PCV13 (n = 166–179)^c	PCV13/PCV13 (n = 122–129)^c vs PPSV23/PCV13 (n = 166–179)^c	PCV13/PCV13 (n = 122–129)^c vs PCV13/PPSV23 (n = 195–209)^c	PCV13/PCV13 (n = 210–220)^c vs PPSV23/PCV13 (n = 208–222)^c
1	1.5	1.5	1.0	1.7
	(1.02, 2.08)	(1.02, 2.25)	(0.72, 1.51)	(1.27, 2.40)
3	1.5	1.1	0.7	1.2
	(1.14, 1.99)	(0.78, 1.44)	(0.52, 0.94)	(0.95, 1.59)
4	1.9	1.8	0.9	1.5
	(1.22, 3.06)	(1.06, 3.00)	(0.58, 1.47)	(1.03, 2.29)
5	1.7	0.7	0.4	1.4
	(1.15, 2.56)	(0.41, 1.04)	(0.25, 0.59)	(0.95, 1.97)
6A	2.2	3.1	1.4	2.2
	(1.36, 3.53)	(1.82, 5.24)	(0.85, 2.32)	(1.42, 3.31)
6B	1.8	2.4	1.3	1.3
	(1.15, 2.91)	(1.43, 4.11)	(0.82, 2.13)	(0.88, 2.04)
7F	2.8	1.7	0.6	1.5
	(1.80, 4.44)	(0.96, 3.00)	(0.37, 0.97)	(0.95, 2.40)
9V	1.7	1.6	1.0	1.2
	(0.99, 2.96)	(0.88, 3.04)	(0.54, 1.70)	(0.70, 1.99)
14	1.1	1.0	0.9	0.8
	(0.73, 1.62)	(0.64, 1.54)	(0.59, 1.41)	(0.57, 1.25)
18C	1.6	1.2	0.7	1.5
	(1.02, 2.39)	(0.71, 1.93)	(0.48, 1.17)	(1.06, 2.12)
19A	1.8	1.4	0.8	1.3
	(1.38, 2.45)	(1.01, 2.04)	(0.58, 1.05)	(0.97, 1.69)
19F	2.2	1.3	0.6	1.8
	(1.53, 3.12)	(0.84, 2.06)	(0.41, 0.88)	(1.21, 2.53)
23F	1.8	3.1	1.7	2.3
	(1.18, 2.82)	(1.89, 5.20)	(1.05, 2.81)	(1.54, 3.42)

Abbreviations: GMT = geometric mean titer; OPA = opsonophagocytic activity; PCV13 = 13-valent pneumococcal conjugate vaccine; PPSV23 = 23-valent pneumococcal polysaccharide vaccine.

Note: only subjects enrolled in the current study are used.

^aRatio of GMT is calculated by back transforming the mean difference between vaccine sequences on the logarithmic scale.

^bCIs for the ratio are back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures.

^cn = Number of subjects with a determinate OPA antibody titer to the given serotype.

Table 4. Comparison of OPA GMTs 1 year after vaccination 2 with 1 year after vaccination 1 in PPSV23-naive subjects (Study 1).

	Vaccine sequence		Vaccine comparison	Vaccine sequence		Vaccine comparison	Vaccine sequence		Vaccine comparison
	GMT^a (95% CI)^c		Ratio^b (95% CI)^d	GMT^a (95% CI)^c		Ratio^b (95% CI)^d	GMT^a (95% CI)^c		Ratio^b (95% CI)^d
Serotype	PCV13/ PPSV23 (n = 195−209)^e	PPSV23 (n = 165−175)^e	PCV13/ PPSV23 vs PPSV23	PCV13/ PCV13 (n = 112−124)^e	PCV13 (n = 112−124)^e	PCV13/ PCV13 vs PCV13	PPSV23/ PCV13 (n = 166−179)^e	PCV13 (n = 316−332)^e	PPSV23/ PCV13 vs PCV13
1	52	45	1.1	52	52	1.0	36	54	0.7
	(40.9, 65.5)	(34.5, 59.8)	(0.80, 1.63)	(39.6, 69.0)	(38.2, 69.5)	(0.85, 1.22)	(27.1, 46.7)	(45.4, 65.0)	(0.48, 0.90)
3	27	26	1.0	18	19	1.0	18	21	0.8
	(22.2, 32.3)	(20.4, 32.5)	(0.77, 1.39)	(14.2, 22.3)	(14.5, 24.1)	(0.82, 1.10)	(14.4, 21.9)	(18.1, 24.9)	(0.64, 1.09)
4	355	332	1.1	376	710	0.5	183	622	0.3
	(264.7, 475.9)	(231.8, 476.2)	(0.68, 1.69)	(264.2, 534.0)	(504.4, 998.7)	(0.41, 0.69)	(127.7, 263.2)	(496.9, 777.7)	(0.20, 0.44)
5	76	49	1.5	29	39	0.8	44	52	0.9
	(58.0, 99.7)	(36.4, 66.9)	(1.03, 2.31)	(20.4, 42.1)	(26.2, 56.7)	(0.67, 0.87)	(32.9, 59.6)	(40.9, 64.8)	(0.59, 1.26)
6A	225	82	2.7	331	540	0.6	102	597	0.2
	(163.6, 308.3)	(54.6, 122.4)	(1.66, 4.55)	(227.1, 483.3)	(347.1, 838.8)	(0.48, 0.79)	(71.4, 146.9)	(466.8, 764.7)	(0.11, 0.26)
6B	593	162	3.7	781	459	1.7	324	420	0.8
	(441.4, 797.3)	(108.9, 241.6)	(2.25, 5.94)	(529.8, 1150.8)	(292.2, 719.9)	(1.32, 2.19)	(225.0, 466.1)	(320.2, 552.0)	(0.49, 1.22)
7F	412	66	6.2	244	146	1.7	145	133	1.1
	(313.1, 541.2)	(44.1, 100.1)	(3.85, 9.98)	(155.7, 383.4)	(89.4, 237.1)	(1.24, 2.26)	(100.3, 210.7)	(99.6, 177.8)	(0.68, 1.76)
9V	221	52	4.2	201	96	2.1	129	85	1.5
	(154.2, 316.0)	(33.7, 80.3)	(2.43, 7.40)	(125.8, 320.2)	(58.3, 158.4)	(1.48, 2.95)	(84.5, 196.5)	(62.7, 115.4)	(0.90, 2.55)
14	416	302	1.4	383	241	1.6	383	250	1.5
	(316.2, 548.2)	(214.2, 425.3)	(0.89, 2.13)	(274.1, 534.2)	(159.6, 364.0)	(1.23, 2.05)	(286.9, 510.6)	(193.5, 324.2)	(1.02, 2.30)
18C	527	319	1.7	398	403	1.0	337	439	0.8
	(401.7, 690.5)	(222.5, 457.3)	(1.06, 2.57)	(274.1, 579.1)	(273.8, 592.0)	(0.82, 1.19)	(240.7, 471.7)	(349.8, 551.0)	(0.52, 1.14)
19A	313	153	2.0	253	203	1.2	170	208	0.8
	(263.1, 372.3)	(117.3, 199.5)	(1.50, 2.78)	(197.2, 325.7)	(151.3, 271.8)	(1.07, 1.46)	(134.4, 214.8)	(175.9, 245.7)	(0.62, 1.08)
19F	426	125	3.4	238	114	2.1	195	147	1.3
	(343.7, 527.7)	(88.8, 176.5)	(2.30, 5.04)	(165.2, 341.7)	(72.7, 177.5)	(1.56, 2.80)	(145.1, 262.1)	(115.1, 187.7)	(0.89, 1.98)
23F	64	30	2.1	104	90	1.1	35	90	0.4
	(47.6, 86.5)	(21.1, 42.1)	(1.37, 3.37)	(67.9, 158.6)	(58.5, 139.9)	(0.89, 1.48)	(25.6, 48.6)	(69.9, 116.6)	(0.26, 0.59)

Abbreviations: GMT = geometric mean titer; OPA = opsonophagocytic activity; PCV13 = 13-valent pneumococcal conjugate vaccine; PPSV23 = 23-valent pneumococcal polysaccharide vaccine.

^aGMTs are calculated using all subjects with available data for the specific blood draw.

^bRatio of GMT is calculated by back transforming the mean difference between vaccine sequence/group on the logarithmic scale.

^cCIs are back transformations of a CI based on the Student t distribution for the mean logarithm of the titers.

^dCIs are back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures.

^en = Number of subjects with a valid and determinate OPA antibody titer to the given serotype.

Table 5. Comparison of OPA GMTs 1 year after vaccination 2 with 1 year after vaccination 1 in PPSV23-preimmunized subjects (Study 2).

	Vaccine sequence		Vaccine comparison	Vaccine sequence		Vaccine comparison
	GMT^a (95% CI)^c		Ratio^b (95% CI)^d	GMT^a (95% CI)^c		Ratio^b (95% CI)^d
Serotype	PCV13/ PCV13 (n = 193–217)^e	PCV13 (n = 193–217)^e	PCV13/ PCV13 vs PCV13	PPSV23/ PCV13 (n = 208−222)^e	PCV13 (n = 200−220)^e	PPSV23/PCV13 vs PCV13
1	38 (30.7, 47.5)	33 (26.4, 41.1)	1.2 (1.03, 1.31)	22 (17.5, 27.8)	33 (26.6, 41.3)	0.7 (0.48, 0.92)
3	19 (16.2, 23.2)	16 (13.2, 19.4)	1.2 (1.07, 1.37)	16 (13.3, 19.2)	16 (13.5, 19.6)	1.0 (0.76, 1.28)
4	267 (198.8, 358.8)	129 (89.0, 186.9)	2.1 (1.60, 2.68)	172 (129.0, 230.1)	123 (85.4, 177.6)	1.4 (0.88, 2.22)
5	57 (44.5, 73.2)	32 (25.0, 41.4)	1.8 (1.55, 2.03)	42 (32.2, 55.6)	31 (24.4, 40.2)	1.4 (0.93, 1.95)
6A	256 (191.2, 341.9)	279 (203.4, 383.4)	0.9 (0.79, 1.07)	115 (84.5, 156.8)	271 (197.5, 370.6)	0.4 (0.27, 0.66)
6B	511 (376.9, 693.4)	403 (290.6, 558.3)	1.3 (1.05, 1.53)	381 (281.9, 513.9)	380 (274.0, 526.3)	1.0 (0.64, 1.56)
7F	175 (127.1, 240.3)	66 (46.3, 95.3)	2.6 (1.98, 3.50)	115 (81.6, 160.9)	61 (43.0, 87.7)	1.9 (1.14, 3.04)
9V	76 (51.6, 112.9)	40 (27.6, 59.1)	1.9 (1.37, 2.61)	68 (47.4, 98.5)	40 (27.8, 58.3)	1.7 (1.01, 2.85)
14	204 (155.6, 268.5)	130 (96.1, 176.2)	1.6 (1.33, 1.86)	240 (181.0, 317.0)	126 (93.0, 170.7)	1.9 (1.26, 2.87)
18C	545 (438.2, 678.0)	436 (340.9, 556.7)	1.3 (1.10, 1.42)	360 (273.6, 474.5)	439 (343.4, 559.9)	0.8 (0.57, 1.19)
19A	235 (196.4, 282.2)	185 (152.8, 229.2)	1.3 (1.14, 1.43)	181 (146.7, 222.9)	183 (151.3, 220.7)	1.0 (0.75, 1.31)
19F	261 (204.9, 333.7)	121 (91.1, 160.0)	2.2 (1.80, 2.60)	158 (119.3, 209.9)	115 (87.4, 151.3)	1.4 (0.93, 2.04)
23F	104 (78.0, 137.4)	60 (44.5, 81.1)	1.7 (1.44, 2.06)	45 (33.5, 59.6)	59 (43.7, 79.4)	0.8 (0.50, 1.15)

Abbreviations: GMT = geometric mean titer; OPA = opsonophagocytic activity; PCV13 = 13-valent pneumococcal conjugate vaccine; PPSV23 = 23-valent pneumococcal polysaccharide vaccine.

^aGMTs are calculated using all subjects with available data for the specific blood draw.

^bRatio of GMT is calculated by back transforming the mean difference between vaccine sequence/group on the logarithmic scale.

^cCIs are back transformations of a CI based on the Student t distribution for the mean logarithm of the titers.

^dCIs for the ratio are back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures.

^en = Number of subjects with a valid and determinate OPA titer to the given serotype.

Figure 1. Serotype-specific OPA GMTs from all study time points from before the first vaccination through 1 year after the second vaccination. The first 3 points for each serotype correspond with data from study 1¹⁰ and study 2.¹¹ Abbreviations: GMT = geometric mean titer; OPA = opsonophagocytic activity.

Greenberg RN, Gurtman A, Frenck RW, Strout C, Jansen KU, Trammel J, Scott DA, Emini EA, Gruber WC, Schmoele-Thoma B. Sequential administration of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine in pneumococcal vaccine-naive adults 60-64 years of age. Vaccine. 2014;32(20):2364–2374. doi:10.1016/j.vaccine.2014.02.002.

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Jackson LA, Gurtman A, Rice K, Pauksens K, Greenberg RN, Jones TR, Scott DA, Emini EA, Gruber WC, Schmoele-Thoma B. Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine in adults 70 years of age and older previously vaccinated with 23-valent pneumococcal polysaccharide vaccine. Vaccine. 2013;31(35):3585–3593. doi:10.1016/j.vaccine.2013.05.010.

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