Safety, reactogenicity, and immunogenicity of a 12-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine in healthy toddlers: results from a phase I, randomized trial

Figures & data

Figure 1. Participant flow chart

N, number of toddlers; ATP, according-to-protocol.

Table 1. Demographic characteristics for study participants (total vaccinated cohort)

	12vPHiD-CV group	PHiD-CV group	Total
	(N = 31)	(N = 30)	(N = 61)
Mean age at vaccination ± SD, months	15.5 ± 3.10	14.4 ± 2.27	15.0 ± 2.75
White/Caucasian-European heritage*, n (%)	30 (96.8)	30 (100)	60 (98.4)
White/Arabic-North African heritage*, n (%)	1 (3.2)	-	1 (1.6)
Male, n (%)	15 (48.4)	12 (40.0)	27 (44.3)

N, number of toddlers in each group; SD, standard deviation; n (%), number (percentage) of toddlers in each category.

Note: *Geographic ancestry data were collected from the children’s parents/legally acceptable representatives (sufficient information was provided by the study staff to answer this query correctly) and a questionnaire regarding ethnicity was filled in by the investigator.

Figure 2. Percentage of toddlers with solicited local (A) and general (B) adverse events within the 7-day period following vaccination (total vaccinated cohort)

Note: Error bars represent 95% confidence intervals.

Table 2. Percentages of toddlers with pneumococcal serotype-specific antibody concentrations ≥0.2 µg/mL and antibody GMCs, by timepoint (according-to-protocol cohort for immunogenicity)

		12vPHiD-CV				PHiD-CV
		N	% (95% CI)	GMC (95% CI)		N	% (95% CI)	GMC (95% CI)
1	Pre	30	63.3 (43.9–80.1)	0.2 (0.1–0.3)		24	41.7 (22.1–63.4)	0.2 (0.1–0.3)
	Post	31	100 (88.8–100)	2.3 (1.7–3.1)		27	100 (87.2–100)	2.8 (2.1–3.8)
4	Pre	28	67.9 (47.6–84.1)	0.3 (0.2–0.5)		26	57.7 (36.9–76.6)	0.3 (0.2–0.4)
	Post	31	100 (88.8–100)	5.2 (4.1–6.6)		27	100 (87.2–100)	4.5 (3.3–6.1)
5	Pre	29	69.0 (49.2–84.7)	0.3 (0.2–0.5)		24	62.5 (40.6–81.2)	0.3 (0.2–0.5)
	Post	31	100 (88.8–100)	3.3 (2.5–4.4)		27	100 (87.2–100)	2.3 (1.5–3.5)
6B	Pre	30	66.7 (47.2–82.7)	0.3 (0.2–0.5)		24	41.7 (22.1–63.4)	0.2 (0.1–0.3)
	Post	31	100 (88.8–100)	5.4 (4.0–7.1)		27	100 (87.2–100)	1.9 (1.5–2.5)
7 F	Pre	30	86.7 (69.3–96.2)	0.8 (0.6–1.1)		24	95.8 (78.9–99.9)	0.7 (0.5–0.9)
	Post	31	100 (88.8–100)	3.8 (3.0–4.7)		27	100 (87.2–100)	3.4 (2.5–4.6)
9 V	Pre	30	90.0 (73.5–97.9)	0.7 (0.5–1.0)		24	83.3 (62.6–95.3)	0.6 (0.3–1.0)
	Post	31	100 (88.8–100)	4.4 (3.3–5.9)		27	100 (87.2–100)	3.6 (2.4–5.5)
14	Pre	30	93.3 (77.9–99.2)	0.9 (0.6–1.5)		24	91.7 (73.0–99.0)	0.8 (0.5–1.2)
	Post	31	100 (88.8–100)	8.3 (6.3–11.0)		27	100 (87.2–100)	7.2 (5.5–9.3)
18 C	Pre	30	83.3 (65.3–94.4)	0.7 (0.4–1.0)		24	79.2 (57.8–92.9)	0.6 (0.4–0.9)
	Post	31	100 (88.8–100)	11.3 (8.3–15.3)		27	100 (87.2–100)	11.2 (8.0–15.6)
19 F	Pre	30	83.3 (65.3–94.4)	1.2 (0.7–2.1)		24	91.7 (73.0–99.0)	0.6 (0.4–0.9)
	Post	31	100 (88.8–100)	17.3 (12.1–24.9)		27	100 (87.2–100)	10.9 (8.0–14.8)
23 F	Pre	30	70.0 (50.6–85.3)	0.4 (0.2–0.5)		24	75.0 (53.3–90.2)	0.4 (0.2–0.7)
	Post	31	100 (88.8–100)	3.5 (2.6–4.6)		27	100 (87.2–100)	3.5 (2.7–4.7)
6A	Pre	30	36.7 (19.9–56.1)	0.2 (0.1–0.3)		25	20.0 (6.8–40.7)	0.1 (0.1–0.1)
	Post	31	100 (88.8–100)	6.0 (3.9–9.1)		26	84.6 (65.1–95.6)	0.8 (0.4–1.3)
19A	Pre	30	66.7 (47.2–82.7)	0.3 (0.2–0.5)		25	36.0 (18.0–57.5)	0.2 (0.1–0.3)
	Post	31	100 (88.8–100)	8.2 (5.5–12.4)		27	96.3 (81.0–99.9)	2.0 (1.2–3.3)

N, number of toddlers with available results in each group; GMC, geometric mean concentration; CI, confidence interval; Pre, pre-vaccination; Post, 1 month post-vaccination.

Table 3. Percentages of toddlers with pneumococcal serotype-specific OPA titers above or equal to the assay serotype-specific LLOQ and OPA GMTs, by timepoint (according-to-protocol cohort for immunogenicity)

		12vPHiD-CV				PHiD-CV
		N	% (95% CI)	GMT (95% CI)		N	% (95% CI)	GMT (95% CI)
6A	Pre	12	25.0 (5.5–57.2)	142.3 (66.4–304.8)		7	28.6 (3.7–71.0)	144.4 (51.8–402.1)
	Post	24	100 (85.8–100)	4515.3 (3426.5–5950.0)		17	82.4 (56.6–96.2)	1165.4 (571.8–2375.1)
19A	Pre	13	30.8 (9.1–61.4)	208.7 (73.0–596.7)		6	50.0 (11.8–88.2)	251.6 (55.2–1145.5)
	Post	25	100 (86.3–100)	5109.3 (3850.7–6779.4)		20	95.0 (75.1–99.9)	2796.3 (1708.7–4576.4)

OPA, opsonophagocytic activity; LLOQ, lower limit of quantitation; N, number of toddlers with available results in each group; GMT, geometric mean titer; CI, confidence interval; Pre, pre-vaccination; Post, 1 month post-vaccination.

Note: The assay LLOQ was 151 for serotype 6A and 143 for serotype 19A.

Table 4. Percentages of toddlers with anti-protein D antibody concentrations ≥100 EL.U/mL and antibody GMCs, by timepoint (according-to-protocol cohort for immunogenicity)

	12vPHiD-CV				PHiD-CV
	N	% (95% CI)	GMC (95% CI)		N	% (95% CI)	GMC (95% CI)
Pre	30	83.3 (65.3–94.4)	315.9 (209.5–476.4)		24	79.2 (57.8–92.9)	244.3 (153.7–388.3)
Post	31	96.8 (83.3–99.9)	1893.8 (1216.7–2947.6)		26	100 (86.8–100)	1493.0 (962.4–2316.1)

N, number of toddlers with available results; EL.U, enzyme-linked immunosorbent assay units; GMC, geometric mean concentration; CI, confidence interval; Pre, pre-vaccination; Post, 1 month post-vaccination.