Phase I Clinical Evaluation of a Synthetic Oligosaccharide-Protein Conjugate Vaccine against Haemophilus influenzae Type b in Human Adult Volunteers

DOI: 10.1128/CVI.00144-06

Article Figures & Data

TABLE 1.

Local and systemic responses of volunteers receiving a single dose of the vaccine under study^a

Sign or symptom	Positive rate (%) for indicated vaccine group^b
	Study 1				Study 2
	A	B	C	D	E	F	G	H
Local
Swelling	0	0	0	0	10	10	10	0
Local pain	20	20	30	0	30	30	30	50
Inflammation	10	0	0	0	0	0	0	0
Erythema	0	0	0	0	0	0	10	0
Systemic
Febricula (37-37.9°C)	30	60	30	80	0	0	30	0
Fever (≥38°C)	0	0	0	10	0	0	10	0
Slight headache	0	10	0	0	0	10	0	10
General uneasiness	0	0	0	10	0	0	0	0

↵ a Each group consisted of 10 human adult volunteers. Groups C and E received the control vaccine Vaxem-Hib (Chiron). All other groups received the vaccine under study.
↵ b Adjuvant used for each group: A, none; B, none; C, Al(OH)₃; D, none; E, AlPO₄; F, none; G, AlPO₄; H, AlPO₄. Vaccine lot used for each group: A, 1019E; B, 1016E; C, 3581; D, 1017E; E, 0101; F, 1024E; G, 1022E; H, 1021E.

TABLE 2.

IgG anti-PRP antibody responses in adult volunteers^a

Study	Vaccine group	Geometric mean of antibody concn (μg/ml)^b		No. of volunteers with a ≥4-fold rise in seroconversion^c
Study	Vaccine group	Before vaccination (IgG [range])	1 mo after vaccination (IgG [range])	No. of volunteers with a ≥4-fold rise in seroconversion^c
1	A	4.38 (1.00-21.43)	84.64 (21.21-1009.7)	10/10
	B	3.91 (1.21-18.33)	82.75 (5.54-1009.7)	8/10
	C	2.95 (0.72-49.13)	54.95 (7.82-1644.5)	9/10
	D	5.53 (1.00-295.88)	189.97 (13.37-1575.7)	9/10
2	E	7.03 (2.69-39.89)	159.17 (33.86-1475.1)	9/10
	F	4.66 (1.16-12.07)	134.29 (12.19-941.33)	10/10
	G	5.47 (0.98-21.98)	101.49 (14.21-1239.1)	9/10
	H	3.86 (0.90-22.90)	56.83 (7.83-163.91)	9/10

↵ a Each group consisted of 10 human adult volunteers. Groups C and E received the control vaccine Vaxem-Hib. All other groups received the vaccine under study.
↵ b There is no significant difference between the IgG geometric mean antibody concentrations for the groups (P > 0.05).
↵ c There is no significant difference between the groups regarding the numbers of volunteers responding with a ≥4-fold rise (P > 0.05).

TABLE 3.

Immunoglobulin class composition for Haemophilus influenzae type b capsular polysaccharide antibodies elicited by vaccination in study 1^a

Vaccine group	Stage of treatment	Geometric mean antibody concn (μg/ml)
Vaccine group	Stage of treatment	IgM (range)^b	IgA (range)^c	IgG^d
A	Preimmunization	0.31 (0-0.63)	1.29 (0-6.51)	4.38
A	Postimmunization	6.83 (0-16.90)	6.31 (0-15.28)	84.64
B	Preimmunization	0.11 (0-0.63)	0.98 (0-6.51)	3.91
B	Postimmunization	3.31 (0-7.70)	7.42 (0-18.48)	82.75
C	Preimmunization	0.24 (0-1.06)	0.23 (0-0.85)	2.95
C	Postimmunization	3.92 (0-10.86)	5.38 (0-17.43)	54.95
D	Preimmunization	0.29 (0-2.27)	2.10 (0-19.11)	5.53
D	Postimmunization	6.99 (0-26.79)	8.29 (1.09-25.32)	189.97

↵ a Group C received the control vaccine Vaxem-Hib. All other groups received the vaccine under study.
↵ b Number of volunteers responding with a ≥4-fold rise in seroconversion for each group: A, 8/10; B, 4/10; C, 4/10; D, 3/10.
↵ c Number of volunteers responding with a ≥4-fold rise in seroconversion for each group: A, 3/10; B, 5/10; C, 4/10; D, 4/10.
↵ d Number of volunteers responding with a ≥4-fold rise in seroconversion for each group: A, 10/10; B, 8/10; C, 9/10; D, 9/10. Ranges for geometric mean antibody concentration are shown in Table 2.

TABLE 4.

Specificities, avidity indexes, and bactericidal activities in vitro of anti-PRP antibodies from sera in study 1^a

Vaccine group	Serum bactericidal activity		Relative avidity		Specificity (PRP_50%)
Vaccine group	Log₂ SBA	Range	Log AI	Range	Specificity (PRP_50%)
A	4.02	2.0-7.0	2.06	1.57-2.68	1.06E−04
B	5.20	3.0-9.0	2.21	1.68-3.04	8.69E−05
C	3.84	2.0-10.0	2.08	1.77-2.60	1.17E−04
D	4.42	2.0-10.0	2.10	1.38-2.68	1.02E−04

↵ a Group C received the control vaccine Vaxem-Hib. All other groups received the vaccine under study. There is no significant difference between the values for the groups (P > 0.05). PRP_50%, geometric mean of the PRP concentration inhibiting 50% of the ELISA.