Safety and immunogenocity of a novel combined Haemophilus influenzae type b–Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine in healthy Chinese children aged 6 months to 5 years old

Figures & data

Figure 1. Trial profile. ATP, according to protocol.

Table 1. Summary of serious adverse event and adverse reactions

		Hib-MenAC group （N = 600）			Control group （N = 598）
6–23 months		n	%	95% CI	n	%	95% CI
SAEs
SAEs within 28 d after each dose	1	0.2	0.0–0.9	2	0.3	0.0–1.2
Overall adverse reactions
Any	281	46.8	42.8–50.9	298	49.8	45.8–53.9
Grade 3	14	2.3	1.3–3.9	13	2.2	1.2–3.7
Injection-site adverse reactions^#
Induration	Any	1	0.2	0.0–0.9	2	0.3	0.0–1.2
	Grade 3	0	0	0.0–0.6	0	0	0.0–0.6
Redness	Any	7	1.2	0.5–2.4	9	1.5	0.7–2.8
	Grade 3	0	0	0.0–0.6	1	0.2	0.0–0.6
Pain	Any	1	0.2	0.0–0.9	4	0.7	0.2–1.7
	Grade 3	0	0	0.0–0.6	0	0	0.0–0.6
Swelling	Any	7	1.2	0.5–2.4	7	1.2	0.5–2.4
	Grade 3	0	0	0.0–0.6	0	0	0.0–0.6
Systemic adverse reactions
Fever	Any	219	36.5	32.6–40.5	240	40.1	36.2–44.2
	Grade 3	14	2.3	1.3–3.9	10	1.7	0.8–3.1
Diarrhea	Any	58	9.7	7.4–12.3	65	10.9	8.5–13.6
	Grade 3	0	0	0.0–0.6	2	0.3	0.0–0.6
Cough	Any	44	7.3	5.4–9.7	45	7.5	5.5–9.9
	Grade 3	0	0	0.0–0.6	0	0	0.0–0.6
Nausea/Vomiting	Any	22	3.7	2.3–5.5	22	3.7	2.3–5.5
	Grade 3	0	0	0.0–0.6	0	0	0.0–0.6
Fatigue	Any	1	1.2	0.0–0.9	2	0.3	0.0–1.2
	Grade 3	0	0	0.0–0.6	0	0	0.0–0.6
Others	Any	0	0	0.0–0.6*	7	1.2	0.5–2.4*
	Grade 3*	0	0	0.0–0.6	0	0	0.0–0.6
		Hib-MenAC group （N = 598）			Control group （N = 599）
2–5 years		n	%	95% CI	n	%	95% CI
SAEs
SAEs within 28 d after each dose	0	0	0.0–0.6	1	0.2	0.0–0.9
Overall adverse reactions
	Any	178	29.8	26.1–33.6	185	30.9	27.2–34.8
	Grade 3	3	0.5	0.1–1.5	6	1	0.4–2.2
Injection-site adverse reactions^#
Induration	Any	4	0.7	0.2–1.7	3	0.5	0.1–1.5
	Grade 3	1	0.2	0.0–0.9	0	0	0.0–0.6
Redness	Any	10	1.7	0.8–3.1	6	1	0.4–2.2
	Grade 3	1	0.2	0.0–0.9	0	0	0.0–0.6
Pain	Any	9	1.5	0.7–2.8	8	1.3	0.6–2.6
	Grade 3	0	0	0.0–0.6	0	0	0.0–0.6
Swelling	Any	10	1.7	0.8–3.1	12	2	1.0–3.5
	Grade 3	1	0.2	0.0–0.9	0	0	0.0–0.6
Erythra	Any	1	0.2	0.0–0.9	0	0	0.0–0.6
	Grade 3	0	0	0.0–0.6	0	0	0.0–0.6
Exanthema	Any	0	0	0.0–0.6	1	0.17	0–0.93
	Grade 3	0	0	0.0–0.6	0	0	0.0–0.6
Systemic adverse reactions
Fever	Any	127	21.2	18.0–24.7	141	23.5	20.2–27.2
	Grade 3	1	0.2	0.0–0.9	6	1	0.4–2.2
Diarrhea	Any	7	1.2	0.5–2.4	8	1.3	0.6–2.6
	Grade 3	0	0	0.0–0.6	0	0	0.0–0.6
Cough	Any	25	4.2	2.7–6.1	27	4.5	3.0–6.5
	Grade 3	0	0	0.0–0.6	0	0	0.0–0.6
Nausea/ Vomiting	Any	4	0.7	0.2–1.7	7	1.2	0.5–2.4
	Grade 3	0	0	0.0–0.6	0	0	0.0–0.6
Fatigue	Any	3	0.5	0.1–1.5	2	0.3	0.0–1.2
		Hib-MenAC group （N = 598）			Control group （N = 599）
2–5 years		n	%	95% CI	n	%	95% CI
	Grade 3	1	0.2	0.0–0.9	0	0	0.0–0.6
Myalgia	Any	0	0	0.0–0.6	4	0.7	0.2–1.7
	Grade 3	0	0	0.0–0.6	0	0	0.0–0.6
Headache	Any	2	0.3	0.0–1.2	2	0.3	0.0–1.2
	Grade 3	0	0	0.0–0.6	0	0	0.0–0.6
Others	Any	0	0	0.0–0.6	2	0.3	0.0–1.2
	Grade 3*	0	0	0.0–0.6	0	0	0.0–0.6

^#, we only reported the data of local adverse reactions on the arm administered with the investigational Hib-MenAC vaccine in the Hib-MenAC group, while we reported pooled local adverse reactions in both arms in the control group.

*, an adverse reaction was one that resulted in an inability to perform usual social and functional activities.

N, number of participants in the ATP cohort for safety.

n, number of participants with the corresponding adverse reaction.

%, incidence of the corresponding adverse reaction.

SAE, serious adverse event.

Table 2. The seroconversion rate of PRP, MenA , MenC after vaccination

Antibody	Group		N	n	%	95% CI for %	RD(%)	lower limit of 95% CI for RD(%)
6–23 months	rSBA-MenA	Hib-MenAC group	551	525	95.3	93.16–96.89	−0.78	−3.17
		Control group	558	536	96.1	94.09–97.51
	rSBA-MenC	Hib-MenAC group	551	535	97.1	95.33–98.33	0.68	−1.40
		Control group	558	538	96.4	94.52–97.80
	PRP	Hib-MenAC group	551	534	96.9	95.11–98.19	1.22	−1.00
		Control group	558	534	95.7	93.67–97.23
	rSBA-MenA	Hib-MenAC group	569	546	96.0	94.00–97.42	2.55	−0.06
		Control group	561	524	93.4	91.02—-95.31
2–5 years	rSBA-MenC	Hib-MenAC group	569	538	94.6	92.36–96.27	−1.53	−3.99
		Control group	561	539	96.1	94.12–97.53
	PRP	Hib-MenAC group	569	538	94.6	92.36–96.27	−3.49	−5.68
		Control group	561	550	98.0	96.52–99.02

N, number of participants in the ATP cohort for immunogenicity.

n, number of participants with the antibody seroconversion after vaccination.

PRP, polyribosylribotol phosphate.

rSBA-MenA, serum bactericidal activity using rabbit complement of N. meningitidis serogroup A;

rSBA-MenC, serum bactericidal activity using rabbit complement of N. meningitidis serogroup C.

%, percentage of subjects with the antibody seroconversion after vaccination.

CI, confidence interval.

RD, rate difference.

Table 3. Porportion of vaccinees with responses to PRP, MenA , MenC during the pre- and post-vaccination phases

				PRP			rSBA-MenA			rSBA-MenC
Group	Timepoint		N	% ≥0.15 ug/mL (95% CI)	% ≥1 ug/mL (95% CI)	GMC (95% CI)	% ≥1:8 (95% CI)	% ≥1:128 (95% CI)	GMT(1: ) (95% CI)	% ≥1:8 (95% CI)	% ≥1:128(95% CI)	GMT(1: )(95% CI)
6–23 months	Hib-MenAC group	Pre-vaccination	551	16.2 (13.2–19.5)	13.4 (10.7–16.6)	0.1 (0.1–0.1)	4.2 (2.7–6.2)	0.4 (0.0–1.3)	1.2 (1.1–1.3)	1.1 (0.4—-2.4)*	0.2 (0.0–1.0)	1.1 (1.0–1.1)
		Post-vaccination	551	98.9 (97.7–99.6)	98.9 (97.7–99.6)	16.2 (14.7–17.8)*	98.6 (97.2–99.4)	80.8 (77.2–84.0)	213.3 (192.5–236.4)	97.6 (96.0–98.7)	66.4 (62.3–70.4)	131.1 (116.9–147.1)
	Control group	Pre-vaccination	558	17.6 (14.5–21.0)	13.4 (11.4–17.3)	0.1 (0.1–0.1)	3.6 (2.2–5.5)	0.5 (0.1–1.6)	1.2 (1.1–1.3)	2.5 (1.4–4.2)*	0.4 (0.0–1.3)	1.1 (1.1–1.1)
		Post-vaccination	558	98.0 (96.5–99.0)	98.0 (96.5–99.0)	20.0 (18.0–22.2)*	98.2 (96.7–99.1)	82.1 (78.6–85.2)	214.3 (194.1–236.7)	98.6 (97.2–99.4)	66.0 (61.9–69.9)	140.5 (126.7–155.8)
2–5 years	Hib-MenAC group	Pre-vaccination	569	42.7 (38.6–46.9)	39.9 (35.8–44.0)	0.3 (0.3–0.4)	6.0 (4.2–8.3)	1.4 (0.6–2.8)	1.3 (1.2–1.4)	6.5 (4.6–8.8)*	1.2 (0.5–2.5)	1.3 (1.2–1.4)*
		Post-vaccination	569	99.8 (99.0–100.0)	99.8 (99.0–100.0)	45.2 (40.3–50.6)*	98.6 (97.3–99.4)	81.4 (77.9–84.5)	204.1 (185.4–224.7)	98.1 (96.6–99.0)	73.1 (69.3–76.7)	189.7 (168.2–214.0)
	Control group	Pre-vaccination	561	44.9 (40.8–49.1)	40.6 (36.6–44.8)	0.4 (0.3–0.4)	6.1 (4.2–8.4)	1.1 (0.4–2.3)	1.3 (1.2–1.4)	3.9 (2.5–5.9)*	0.7 (0.2–1.8)	1.2 (1.1–1.3)*
		Post-vaccination	561	100.0 (99.3–100.0)	100.0 (99.3–100.0)	70.7 (63.4–78.7)*	97.7 (96.1–98.8)	82.7 (79.3–85.8)	207.5 (186.9–230.4)	98.4 (97.0–99.3)	74.7 (70.9–78.2)	195.79 (175.0–219.1)

*, Significant difference between Hib-MenAC group and control group.

N, number of participants in the ATP cohort for immunogenicity.

PRP, polyribosylribotol phosphate.

rSBA-MenA, serum bactericidal activity using rabbit complement of N. meningitidis serogroup A.

rSBA-MenC, serum bactericidal activity using rabbit complement of N. meningitidis serogroup C.

%, percentage of participants with concentration above the specified cut-off.

GMC, geometric mean concentration.

GMT, geometric mean titer.

CI, confidence interval.