Safety, immunogenicity and persistence of immune response to the combined diphtheria, tetanus, acellular pertussis, poliovirus and Haemophilus influenzae type b conjugate vaccine (DTPa-IPV/Hib) administered in Chinese infants

Figures & data

Table 1. Summary of demographic characteristics (Total vaccinated cohorts).

Pilot studyCharacteristics	Group A(N = 25)	Group B(N = 25)	Total (N = 50)
Age (weeks), mean (SD)	10.1 (1.36)	14.2 (1.18)	12.1 (2.40)
Gender
Female, n (%)	7 (28.0)	11 (44.0)	18 (36.0)
Male, n (%)	18 (72.0)	14 (56.0)	32 (64.0)
Primary vaccination study
Characteristics	Group A(N = 330)	Group B(N = 324)	Control(N = 330)	Total(N = 984)
Age (weeks), mean (SD)	9.9 (1.12)	14.3 (1.14)	9.9 (1.17)	11.3 (2.37)
Gender
Female, n (%)	155 (47.0)	147 (45.4)	141 (42.7)	443 (45.0)
Male, n (%)	175 (53.0)	177 (54.6)	189 (57.3)	541 (55.0)
Booster vaccination study^*
Characteristics	Group A(N = 272)	Group B(N = 273)	Control(N = 280)	Total(N = 825)
Age (weeks), mean (SD)	19.5 (0.9)	19.4 (0.9)	19.5 (1.0)	19.5 (0.9)
Gender
Female, n (%)	131 (48.2)	126 (46.2)	120 (42.9)	377 (45.7)
Male, n (%)	141 (51.8)	147 (53.8)	160 (57.1)	448 (54.3)

N, total number of participants; n (%), number (percentage) of participants in a given category; SD, standard deviation.

Group A, infants who received DTPa-IPV/Hib vaccine at 2, 3, 4 months of age.

Group B, infants who received DTPa-IPV/Hib vaccine at 3, 4, 5 months of age.

Control, infants who received DTPa/Hib and IPV vaccines at 2, 3, 4 months of age.

* In the Booster study, all children received booster vaccination with the same vaccines, i.e. DTPa/Hib and IPV.

Figure 1. Participant flow in the Primary and Booster vaccination studies. Group A, infants who received DTPa-IPV/Hib vaccine at 2, 3, 4 months of age; Group B, infants who received DTPa-IPV/Hib vaccine at 3, 4, 5 months of age; Control, infants who received DTPa/Hib and IPV vaccines at 2, 3, 4 months of age N, number of participants; TVC, total vaccinated cohort; ATP, according-to-protocol; SAE, serious adverse event; AE, adverse event. One participant was not included in the TVC due to consent withdrawal before vaccination.

Figure 2. Solicited local and general symptoms reported within 4 d (day 0–3) after vaccination with DTPa-IPV/Hib in the Pilot study (A), or with DTPa-IPV/Hib or DTPa/Hib and IPV in the Primary vaccination study (B) or with or DTPa/Hib and IPV in the Booster vaccination study (C) (Total vaccinated cohorts). Group A, infants who received DTPa-IPV/Hib vaccine at 2, 3, 4 months of age; Group B, infants who received DTPa-IPV/Hib vaccine at 3, 4, 5 months of age; Control, infants who received DTPa/Hib and IPV vaccines at 2, 3, 4 months of age; %, percentage of participants. The error bars indicate 95% confidence intervals.

Table 2. Seroprotection/seropositivity rates and geometric mean antibody concentrations/titers before and one month after third dose/booster with DTPa-IPV/Hib or DTPa/Hib and IPV vaccines in the Primary and Booster vaccination studies (ATP cohort for immunogenicity).

			Primary Vaccination						Booster Vaccination^*
Antibody	Groups	Timepoint	N	n (%)	95% CI	GMC/GMT	95% CI	N	n (%)	95% CI	GMC/GMT	95% CI
Anti-DT(≥0.1 IU/ml)	Group A	PRE	147	3 (2.0)	0.4–5.8	0.052	0.050–0.053	265	235 (88.7)	84.2–92.2	0.174	0.162–0.187
		POST	147	146 (99.3)	96.3–100.0	0.719	0.661–0.782	265	265 (100.0)	98.6–100.0	1.341	1.239–1.451
	Group B	PRE	157	2 (1.3)	0.2–4.5	0.051	0.050–0.052	267	245 (91.8)	87.8–94.8	0.189	0.176–0.202
		POST	156	156 (100.0)	97.7–100.0	0.753	0.699–0.812	268	268 (100.0)	98.6–100.0	1.504	1.377–1.643
	Control	PRE	151	1 (0.7)	0.0–3.6	0.051	0.049–0.052	272	228 (83.8)	78.9–88.0	0.154	0.142–0.166
		POST	147	147 (100.0)	97.5–100.0	0.613	0.565–0.666	270	270 (100.0)	98.6–100.0	1.227	1.134–1.326
Anti-TT(≥0.1 IU/ml)	Group A	PRE	147	2 (1.4)	0.2–4.8	0.051	0.050–0.052	266	264 (99.2)	97.3–99.9	0.455	0.429–0.483
		POST	147	147 (100.0)	97.5–100.0	4.118	3.779–4.488	266	266 (100.0)	98.6–100.0	4.862	4.614–5.124
	Group B	PRE	157	4 (2.5)	0.7–6.4	0.052	0.050–0.054	268	266 (99.3)	97.3–99.9	0.511	0.482–0.542
		POST	156	156 (100.0)	97.7–100.0	4.124	3.796–4.479	268	268 (100.0)	98.6–100.0	4.927	4.693–5.173
	Control	PRE	151	0 (0.0)	0.0–2.4	0.050	0.050–0.050	271	268 (98.9)	96.8–99.8	0.380	0.357–0.403
		POST	147	147 (100.0)	97.5–100.0	3.618	3.339–3.921	272	272 (100.0)	98.7–100.0	4.371	4.161–4.591
Anti-PRP(≥0.15 µg/ml)	Group A	PRE	146	25 (17.1)	11.4–24.2	0.127	0.104–0.154	266	221 (83.1)	78.0–87.4	2.308	1.878–2.836
		POST	147	142 (96.6)	92.2–98.9	5.601	4.676–6.709	266	264 (99.2)	97.3–99.9	35.178	30.617–40.418
	Group B	PRE	157	32 (20.4)	14.4–27.5	0.135	0.112–0.163	268	229 (85.4)	80.6–89.4	2.743	2.245–3.352
		POST	157	155 (98.7)	95.5–99.8	9.396	8.032–10.992	268	268 (100.0)	98.6–100	49.023	43.649–55.058
	Control	PRE	151	35 (23.2)	16.7–30.7	0.150	0.122–0.185	273	234 (85.7)	81.0–89.6	2.407	1.993–2.908
		POST	150	133 (88.7)	82.5–93.3	2.826	2.235–3.572	273	271 (99.3)	97.4–99.9	27.682	24.251–31.598
Anti-PT(≥5 EU/ml)	Group A	PRE	147	23 (15.6)	10.2–22.5	2.9	2.8–3.1	266	254 (95.5)	92.3–97.6	10.3	9.5–11.1
		POST	147	147 (100.0)	97.5–100.0	108.7	99.2–119.1	266	266 (100.0)	98.6–100.0	138.5	132.0–145.3
	Group B	PRE	157	11 (7.0)	3.5–12.2	2.7	2.6–2.8	268	258 (96.3)	93.2–98.2	12.2	11.3–13.1
		POST	156	156 (100.0)	97.7–100.0	114.7	105.4–124.8	268	268 (100.0)	98.6–100.0	146.2	139.7–153.0
	Control	PRE	151	16 (10.6)	6.2–16.6	2.8	2.6–2.9	273	253 (92.7)	88.9–95.5	10.3	9.5–11.2
		POST	148	147 (99.3)	96.3–100.0	97.1	88.3–106.8	273	273 (100.0)	98.7–100.0	126.8	120.4–133.5
Anti-FHA(≥5 EU/ml)	Group A	PRE	147	19 (12.9)	8.0–19.4	2.9	2.7–3.1	266	256 (96.2)	93.2–98.2	12.7	11.8–13.6
		POST	147	147 (100.0)	97.5–100.0	87.7	79.9–96.3	266	266 (100.0)	98.6–100.0	124.6	119.2–130.2
	Group B	PRE	157	9 (5.7)	2.7–10.6	2.6	2.5–2.7	268	262 (97.8)	95.2–99.2	14.3	13.4–15.2
		POST	156	156 (100.0)	97.7–100.0	87.6	79.6–96.4	268	268 (100.0)	98.6–100.0	124.0	119.2–129.0
	Control	PRE	151	24 (15.9)	10.5–22.7	2.9	2.7–3.1	273	255 (93.4)	89.8–96.0	12.3	11.4–13.3
		POST	148	147 (99.3)	96.3–100.0	76.3	68.5–85.0	273	273 (100.0)	98.7–100.0	120.8	115.3–126.6
Anti-PRN(≥5 EU/ml)	Group A	PRE	147	6 (4.1)	1.5–8.7	2.6	2.5–2.7	266	254 (95.5)	92.3–97.6	9.2	8.7–9.6
		POST	147	147 (100.0)	97.5–100.0	44.8	42.0–47.9	266	266 (100.0)	98.6–100.0	57.3	55.6–59.1
	Group B	PRE	157	4 (2.5)	0.7–6.4	2.6	2.5–2.6	268	260 (97.0)	94.2–98.7	9.7	9.2–10.2
		POST	156	156 (100.0)	97.7–100.0	43.7	41.3–46.3	268	268 (100.0)	98.6–100.0	59.9	58.1–61.8
	Control	PRE	151	3 (2.0)	0.4–5.7	2.5	2.5–2.6	273	260 (95.2)	92.0–97.4	9.0	8.5–9.5
		POST	148	147 (99.3)	96.3–100.0	43.2	39.8–47.0	273	273 (100.0)	98.7–100.0	57.2	55.3–59.1
Anti-poliovirus type 1	Group A	PRE	146	63 (43.2)	35.0–51.6	9.4	7.7–11.5	266	253 (95.1)	91.8–97.4	72.0	62.0–83.7
		POST	147	147 (100.0)	97.5–100.0	1143.7	952.7–1372.9	265	265 (100.0)	98.6–100.0	3512.2	3159.7–3904.1
	Group B	PRE	157	62 (39.5)	31.8–47.6	7.1	6.2–8.2	268	262 (97.8)	95.2–99.2	96.3	82.8–112.0
		POST	157	157 (100.0)	97.7–100.0	1328.9	1137.6–1552.4	268	268 (100.0)	98.6–100.0	3410.9	3081.7–3775.4
	Control	PRE	151	69 (45.7)	37.6–54.0	9.2	7.7–11.0	273	263 (96.3)	93.4–98.2	75.9	65.7–87.6
		POST	150	150 (100.0)	97.6–100.0	533.6	469.5–606.4	273	273 (100.0)	98.7–100.0	3386.8	3078.0–3726.6
Anti-poliovirus type 2	Group A	PRE	146	43 (29.5)	22.2–37.6	6.3	5.5–7.2	266	243 (91.4)	87.3–94.4	56.5	46.2–69.0
		POST	147	147 (100.0)	97.5–100.0	416.2	344.5–502.8	265	265 (100.0)	98.6–100.0	1931.2	1721.7–2166.2
	Group B	PRE	157	32 (20.4)	14.4–27.5	5.0	4.6–5.5	268	256 (95.5)	92.3–97.7	64.1	53.8–76.4
		POST	157	157 (100.0)	97.7–100.0	458.6	385.6–545.5	268	268 (100.0)	98.6–100.0	2237.9	2001.6–2502.1
	Control	PRE	151	54 (35.8)	28.1–44.0	6.9	6.0–8.0	273	244 (89.4)	85.1–92.8	41.9	35.0–50.0
		POST	150	150 (100.0)	97.6–100.0	186.4	160.4–216.5	273	273 (100.0)	98.7–100.0	1886.1	1679.6–2117.9
Anti-poliovirus type 3	Group A	PRE	146	29 (19.9)	13.7–27.3	5.8	5.0–6.8	266	249 (93.6)	90.0–96.2	72.6	61.1–86.3
		POST	147	147 (100.0)	97.5–100.0	1478.8	1210.6–1806.5	265	265 (100.0)	98.6–100.0	5237.8	4671.8–5872.3
	Group B	PRE	157	18 (11.5)	6.9–17.5	4.9	4.3–5.6	268	254 (94.8)	91.4–97.1	79.4	65.8–95.8
		POST	157	157 (100.0)	97.7–100.0	1411.6	1175.3–1695.3	268	268 (100.0)	98.6–100.0	5438.5	4846.8–6102.4
	Control	PRE	151	34 (22.5)	16.1–30.0	5.7	5.1–6.4	273	250 (91.6)	87.6–94.6	60.3	50.8–71.6
		POST	150	150 (100.0)	97.6–100.0	820.7	698.5–964.4	273	273 (100.0)	98.7–100.0	5141.2	4650.1–5684.2

Group A, infants who received the DTPa-IPV/Hib vaccine at 2, 3, 4 months of age in the Primary study; Group B, infants who received DTPa-IPV/Hib vaccine at 3, 4, 5 months of age in the Primary study; Control, infants who received DTPa/Hib and IPV vaccines separately at 2, 3, 4 months of age in the Primary study; n, number of infants with concentration equal to or above the specified value; %, percentage of infants with concentration equal to or above the specified value; ATP, according-to-protocol; PRE, pre-vaccination blood sampling timepoint; POST, post-vaccination blood sampling timepoint, one month after the third dose; 95% CI, 95% confidence interval; LL, lower limit; UL, upper limit; GMT, geometric mean titer; GMC, geometric mean concentration; anti-DT, anti-diphtheria toxoid; anti-TT, anti-tetanus toxoid; anti-PRP, anti-polyribosyl-ribitol-phosphate; anti-PT, anti-pertussis toxoid; anti-FHA, anti-filamentous hemagglutinin; anti-PRN, anti-pertactin; IU/ml, international units per milliliter; EU/ml, ELISA units per milliliter.

* In the Booster study, all children received booster vaccination with the same vaccines, i.e., DTPa/Hib and IPV.