Safety and immunogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Nigerian children

Figures & data

Figure 1. Trial profile. Note: An issue was identified with the informed consent obtained for one child and the child’s parents didn’t permit GlaxoSmithKline Vaccines to use the child’s data. As a result, the data of the child, who had an SAE that was not considered to be related to the study medication by the investigator, are not detailed and were not used in the analysis.

Table 1. Demographic characteristics (total vaccinated cohort)

	PHiD-CV booster group (n = 68)	PHiD-CV catch-up group (n = 36)
Gender (%), female/male	42.6/57.4	47.2/52.8
Mean age ± SD (months) at booster dose/first catch-up dose	16.7 ± 1.0	16.4 ± 0.9
Mean weight ± SD (kg) at booster dose/first catch-up dose	10.3 ± 1.5	9.8 ± 1.2

SD, standard deviation; N, number of children.

Table 2. Incidences of solicited local and general symptoms per dose (total vaccinated cohort)

		PHiD-CV booster group n = 68		PHiD-CV catch-up group dose 1 n = 36		PHiD-CV catch-up group dose 2 n = 36
Solicited local symptom	Intensity	n	% (95% CI)	n	% (95% CI)	n	% (95% CI)
Pain	Any	25	36.8 (25.4–49.3)	11	30.6 (16.3–48.1)	5	13.9 (4.7–29.5)
	Grade 3	0	0.0 (0.0–5.3)	0	0.0 (0.0–9.7)	0	0.0 (0.0–9.7)
Redness	Any	1	1.5 (0.0–7.9)	1	2.8 (0.1–14.5)	0	0.0 (0.0–9.7)
	>30 mm	0	0.0 (0.0–5.3)	1	2.8 (0.1–14.5)	0	0.0 (0.0–9.7)
Swelling	Any	2	2.9 (0.4–10.2)	2	5.6 (0.7–18.7)	0	0.0 (0.0–9.7)
	>30 mm	2	2.9 (0.4–10.2)	1	2.8 (0.1–14.5)	0	0.0 (0.0–9.7)
Solicited general symptom	Intensity	n	% (95% CI)	n	% (95% CI)	n	% (95% CI)
Drowsiness	Any	2	2.9 (0.4–10.2)	0	0.0 (0.0–9.7)	0	0.0 (0.0–9.7)
	Grade 3	0	0.0 (0.0–5.3)	0	0.0 (0.0–9.7)	0	0.0 (0.0–9.7)
	Related	2	2.9 (0.4–10.2)	0	0.0 (0.0–9.7)	0	0.0 (0.0–9.7)
Fever (axillary temperature)	≥37.5 °C	8	11.8 (5.2–21.9)	2	5.6 (0.7–18.7)	1	2.8 (0.1–14.5)
	>39.5 °C	0	0.0 (0.0–5.3)	1	2.8 (0.1–14.5)	0	0.0 (0.0–9.7)
	Related	8	11.8 (5.2–21.9)	2	5.6 (0.7–18.7)	1	2.8 (0.1–14.5)
Irritability	Any	2	2.9 (0.4–10.2)	0	0.0 (0.0–9.7)	0	0.0 (0.0–9.7)
	Grade 3	0	0.0 (0.0–5.3)	0	0.0 (0.0–9.7)	0	0.0 (0.0–9.7)
	Related	2	2.9 (0.4–10.2)	0	0.0 (0.0–9.7)	0	0.0 (0.0–9.7)
Loss of appetite	Any	1	1.5 (0.0–7.9)	1	2.8 (0.1–14.5)	0	0.0 (0.0–9.7)
	Grade 3	0	0.0 (0.0–5.3)	0	0.0 (0.0–9.7)	0	0.0 (0.0–9.7)
	Related	1	1.5 (0.0–7.9)	1	2.8 (0.1–14.5)	0	0.0 (0.0–9.7)

N, number of subjects with at least one documented dose; n/%, number/percentage of subjects reporting the symptom at least once; CI, confidence interval; Related, solicited symptom assessed by the investigator as causally related to study vaccination. Pain of grade 3 intensity, the limb was spontaneously painful or the child cried when the limb was moved passively; grade 3 redness/swelling, diameter > 30 mm. Drowsiness of grade 3 intensity, prevented normal activity; grade 3 fever, axillary temperature > 39.5 °C; grade 3 irritability, crying that could not be comforted/prevented normal activity; grade 3 loss of appetite, child did not eat at all. PHiD-CV booster group received PHiD-CV booster dose co-administered with Infanrix™ (DTPa) booster dose. PHiD-CV catch-up group received two PHiD-CV catch-up doses, the first co-administered with Infanrix™ booster dose.

Figure 2. (A) Geometric mean antibody concentrations (GlaxoSmithKline’s 22F-inhibition ELISA, binary logarithmic scale, ATP cohort for immunogenicity) and (B) opsonophagocytic geometric mean titers against individual pneumococcal serotypes (decimal logarithmic scale, ATP cohort for immunogenicity). Note: Post-pri, 1 mo after 3-dose priming (at approximately 5 mo of age) with PHiD-CV in PHiD-CV booster group and control vaccine in PHiD-CV catch-up group; Pre-bst/catch-up, before booster dose in PHiD-CV booster group or before first catch-up dose in PHiD-CV catch-up group (15 to 21 mo of age); Post-bst/catch-up, 1 mo after booster dose in PHiD-CV booster group (16 to 22 mo of age) or 1 mo after second catch-up dose in PHiD-CV catch-up group (18 to 24 mo of age). Error bars represent 95% confidence intervals.

Table 3. 22F-ELISA antibody and opsonophagocytic responses against individual pneumococcal serotypes 1 mo after vaccination (ATP cohort for immunogenicity)

		ELISA antibody concentration, % ≥ 0.2 µg/ml (95% CI)				OPA titer, % ≥ 8 (95% CI)
		PHiD-CV booster		PHiD-CV 2-dose catch-up		PHiD-CV booster		PHiD-CV 2-dose catch-up
PHiD-CV serotypes	Timing	N		N		N		N
1	Post-priming	68	100 (94.7–100)	31	6.5 (0.8–21.4)	31	93.5 (78.6–99.2)	17	5.9 (0.1–28.7)
	Pre-booster/catch-up	68	61.8 (49.2–73.3)	35	2.9 (0.1–14.9)	-	-	-	–
	Post-booster/catch-up	67	100 (94.6–100)	35	100 (90.0–100)	66	98.5 (91.8–100)	35	94.3 (80.8–99.3)
4	Post-priming	68	100 (94.7–100)	35	8.6 (1.8–23.1)	31	100 (88.8–100)	16	6.3 (0.2–30.2)
	Pre-booster/catch-up	68	76.5 (64.6–85.9)	35	11.4 (3.2–26.7)	-	-	-	-
	Post-booster/catch-up	67	100 (94.6–100)	35	100 (90.0–100)	65	100 (94.5–100)	35	100 (90.0–100)
5	Post-priming	68	100 (94.7–100)	32	3.1 (0.1–16.2)	31	96.8 (83.3–99.9)	16	0.0 (0.0–20.6)
	Pre-booster/catch-up	68	82.4 (71.2–90.5)	35	11.4 (3.2–26.7)	-	-	-	-
	Post-booster/catch-up	67	100 (94.6–100)	35	100 (90.0–100)	67	100 (94.6–100)	35	91.4 (76.9–98.2)
6B	Post-priming	68	89.7 (79.9–95.8)	35	0.0 (0.0–10.0)	31	93.5 (78.6–99.2)	17	11.8 (1.5–36.4)
	Pre-booster/catch-up	68	86.8 (76.4–93.8)	35	11.4 (3.2–26.7)	-	-	-	-
	Post-booster/catch-up	67	98.5 (92.0–100)	35	82.9 (66.4–93.4)	66	97.0 (89.5–99.6)	31	77.4 (58.9–90.4)
7F	Post-priming	68	100 (94.7–100)	33	3.0 (0.1–15.8)	31	100 (88.8–100)	14	64.3 (35.1–87.2)
	Pre-booster/catch-up	68	91.2 (81.8–96.7)	35	11.4 (3.2–26.7)	-	-	-	-
	Post-booster/catch-up	67	100 (94.6–100)	35	100 (90.0–100)	67	100 (94.6–100)	35	100 (90.0–100)
9V	Post-priming	68	100 (94.7–100)	35	11.4 (3.2–26.7)	31	100 (88.8–100)	15	20.0 (4.3–48.1)
	Pre-booster/catch-up	67	95.5 (87.5–99.1)	35	11.4 (3.2–26.7)	-	-	-	-
	Post-booster/catch-up	67	98.5 (92.0–100)	35	100 (90.0–100)	66	100 (94.6–100)	35	100 (90.0–100)
14	Post-priming	68	98.5 (92.1–100)	35	28.6 (14.6–46.3)	31	100 (88.8–100)	15	13.3 (1.7–40.5)
	Pre-booster/catch-up	68	97.1 (89.8–99.6)	35	31.4 (16.9–49.3)	-	-	-	-
	Post-booster/catch-up	67	100 (94.6–100)	35	100 (90.0–100)	66	100 (94.6–100)	35	100 (90.0–100)
18C	Post-priming	68	100 (94.7–100)	35	5.7 (0.7–19.2)	31	96.8 (83.3–99.9)	17	5.9 (0.1–28.7)
	Pre-booster/catch-up	68	98.5 (92.1–100)	35	11.4 (3.2–26.7)	-	-	-	-
	Post-booster/catch-up	67	100 (94.6–100)	35	100 (90.0–100)	67	94.0 (85.4–98.3)	35	100 (90.0–100)
19F	Post-priming	68	98.5 (92.1–100)	34	32.4 (17.4–50.5)	31	93.5 (78.6–99.2)	17	5.9 (0.1–28.7)
	Pre-booster/catch-up	67	88.1 (77.8–94.7)	35	34.3 (19.1–52.2)	-	-	-	-
	Post-booster/catch-up	67	100 (94.6–100)	35	97.1 (85.1–99.9)	65	95.4 (87.1–99.0)	34	85.3 (68.9–95.0)
23F	Post-priming	68	97.1 (89.8–99.6)	35	2.9 (0.1–14.9)	30	93.3 (77.9–99.2)	14	21.4 (4.7–50.8)
	Pre-booster/catch-up	68	70.6 (58.3–81.0)	35	2.9 (0.1–14.9)	-	-	-	-
	Post-booster/catch-up	67	98.5 (92.0–100)	35	88.6 (73.3–96.8)	67	98.5 (92.0–100)	35	91.4 (76.9–98.2)
Cross-reactive serotypes
6A	Post-priming	68	38.2 (26.7–50.8)	31	0.0 (0.0–11.2)	31	25.8 (11.9–44.6)	16	18.8 (4.0–45.6)
	Pre-booster/catch-up	68	48.5 (36.2–61.0)	35	17.1 (6.6–33.6)	-	-	-	-
	Post-booster/catch-up	67	80.6 (69.1–89.2)	35	51.4 (34.0–68.6)	61	82.0 (70.0–90.6)	34	82.4 (65.5–93.2)
19A	Post-priming	68	60.3 (47.7–72.0)	31	12.9 (3.6–29.8)	31	45.2 (27.3–64.0)	17	0.0 (0.0–19.5)
	Pre-booster/catch-up	68	48.5 (36.2–61.0)	35	25.7 (12.5–43.3)	-	-	-	-
	Post-booster/catch-up	67	85.1 (74.3–92.6)	35	88.6 (73.3–96.8)	66	77.3 (65.3–86.7)	35	85.7 (69.7–95.2)

N, number of children with available results; CI, confidence interval; Post-priming, 1 mo after 3-dose priming (at approximately 5 mo of age) with PHiD-CV in PHiD-CV booster group and control vaccine in PHiD-CV catch-up group; Pre-booster/catch-up, before booster dose in PHiD-CV booster group or before first catch-up dose in PHiD-CV catch-up group (15 to 21 mo of age); Post-booster/catch-up, 1 mo after booster dose in PHiD-CV booster group (16 to 22 mo of age) or 1 mo after second catch-up dose in PHiD-CV catch-up group (18 to 24 mo of age).

Figure 3. ELISA antibody responses (with 95% confidence intervals) against protein D (logarithmic scale, ATP cohort for immunogenicity). Note: Post-priming, 1 mo after 3-dose priming (at approximately 5 mo of age) with PHiD-CV in PHiD-CV booster group and control vaccine in PHiD-CV catch-up group; Pre-booster/catch-up, before booster dose in PHiD-CV booster group or before first catch-up dose in PHiD-CV catch-up group (15 to 21 mo of age); Post-booster/catch-up, 1 mo after booster dose in PHiD-CV booster group (16 to 22 mo of age) or 1 mo after second catch-up dose in PHiD-CV catch-up group (18 to 24 mo of age).