Immunogenicity and safety of different formulations of an adjuvanted glycoprotein D genital herpes vaccine in healthy adults

Figures & data

Figure 1. Flow diagram illustrating enrolment, randomization and follow-up of study participants. Group 1 = gD-2t 40 μg, Group 2 = gD-2t 80 μg, Group 3 = gD-2t 20 μg, Group 4 = gD-2t 20 μg, Group 5 = gD-2t 20 μg. Vaccine formulations administered to groups 1 to 4 contained phenoxyethanol preservative and those administered to group 5 contained thiomersal preservative. The vaccine formulations administered to groups 1–3 and 5 contained Al(OH)₃. The vaccine formulations administered to group 4 contained AlPO₄.

Table 1. Anti HSV-2 candidate vaccine formulations administered during the study

Group	gD-2t (μg)	Aluminum salt	Adjuvant	Preservative	Volume (ml)/ dose	Lot
1	40	500 μg Al(OH)3	MPL	Phenoxyethanol	0.5	DGD13A2
2	80	500 μg Al(OH)3	MPL	Phenoxyethanol	0.5	DGD14A2
3	20	500 μg Al(OH)3	MPL	Phenoxyethanol	0.5	DGD12A2
4	20	500 μg AlPO4	MPL	Phenoxyethanol	0.5	DGD16A2
5	20	500 μg Al(OH)3	MPL	Thiomersal	1.0	DGD11A4

Table 2. Demographic characteristics of vaccinated participants

			Mean ± SD	Range (min-max)
	Gender	N	(years)	(years)
Group 1	Men Women Total	14 16 30	22.9 ± 4.1 22.5 ± 5.0 22.7 ± 4.5	18–36 19–39 18–39
Group 2	Men Women Total	13 17 30	22.0 ± 5.9 21.5 ± 4.3 21.7 ± 5.0	18–39 18–37 18–39
Group 3	Men Women Total	17 13 30	22.7 ± 4.7 22.7 ± 5.6 22.7 ± 5.0	18–38 18–38 18–38
Group 4	Men Women Total	19 11 30	22.8 ± 6.0 21.3 ± 2.3 22.2 ± 4.9	18–42 19–25 18–42
Group 5	Men Women Total	17 13 30	22.5 ± 5.4 21.9 ± 2.9 22.2 ± 4.5	18–42 18–30 18–42
All groups	Men Women Total	80 70 150	22.6 ± 5.2 22.0 ± 4.2 22.3 ± 4.7	18–42 18–39 18–42

Group 1 = gD-2t 40 μg, Group 2 = gD-2t 80 μg, Group 3 = gD-2t 20 μg, Group 4 = gD-2t 20 μg, Group 5 = gD-2t 20 μg; N, number of subjects in a given category; SD, standard deviation.

Figure 2. Geometric mean gD specific antibodies (panel (A) and HSV neutralizing antibodies (panel (B) levels by study visit in each treatment group. Group 1 = gD-2t 40 μg, Group 2 = gD-2t 80 μg, Group 3 = gD-2t 20 μg, Group 4 = gD-2t 20 μg, Group 5 = gD-2t 20 μg. GMT, geometric mean antibody titer; CI, confidence interval; M, month.

Figure 3. Levels of integrated stimulation index (panel (A), interleukin-2 (panel (B), γ interferon (panel (C) by study visit in each treatment group. Group 1 = gD-2t 40 μg, Group 2 = gD-2t 80 μg, Group 3 = gD-2t 20 μg, Group 4 = gD-2t 20 μg, Group 5 = gD-2t 20 μg. ISI, integrated stimulation index; IL-2, interleukin-2; γ-IFN, gamma interferon; M, month.

Table 3. Incidence of solicited symptoms (overall/dose) on Days 0–3 post-vaccination

	Group 1 n = 90	Group 2 n = 87	Group 3 n = 90	Group 4 n = 88	Group 5 n = 90
	n (%)	n (%)	n (%)	n (%)	n (%)
At least one symptom	85 (94.4)	80 (90.9)	82 (91.1)	87 (98.9)	85 (94.4)
Local symptoms
Muscle stiffness	71 (78.9)	71 (81.6)	79 (87.8)	79 (89.9)	79 (87.8)
Grade 3	1 (1.1)	1 (1.1)	1 (1.1)	2 (2.3)	1 (1.1)
Redness	15 (16.7)	19 (21.8)	22 (24.4)	20 (22.7)	24 (26.7)
Grade 3	0 (0.0)	2 (2.3)	0 (0.0)	0 (0.0)	0 (0.0)
Soreness	55 (61.1)	50 (57.5)	62 (68.9)	62 (70.5)	57 (63.3)
Grade 3	1 (1.1)	1 (1.1)	0 (0.0)	2 (2.3)	3 (3.3)
Swelling	6 (6.7)	16 (18.4)	17 (18.9)	18 (20.5)	18 (20.0)
Grade 3	0 (0.0)	0 (0.0)	0 (0.0)	1 (1.1)	0 (0.0)
General symptoms
Fatigue	12 (13.3)	15 (17.2)	13 (14.4)	15 (17.0)	14 (15.6)
Grade 3	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	1 (1.1)
Headache	15 (16.7)	17 (19.5)	13 (14.4)	8 (9.1)	22 (24.4)
Grade 3	0 (0.0)	0 (0.0)	0 (0.0)	1 (1.1)	0 (0.0)
Malaise	2 (2.2)	7 (8.0)	8 (8.9)	4 (4.5)	6 (6.7)
Grade 3	1 (1.1)	0 (0.0)	1 (1.1)	0 (0.0)	1 (1.1)
Fever	1 (1.1)	1 (1.1)	4 (4.4)	2 (2.3)	7 (7.8)
Grade 3	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	1 (1.1)

Group 1 = gD-2t 40 μg, Group 2 = gD-2t 80 μg, Group 3 = gD-2t 20 μg, Group 4 = gD-2t 20 μg, Group 5 = gD-2t 20 μg; n = number of documented doses; n /% = number /% of documented doses with the specified symptom

Table 4. Most frequently reported (≥ 5 cases) unsolicited symptoms

	Group 1 n = 90	Group 2 n = 87	Group 3 n = 90	Group 4 n = 88	Group 5 n = 90	Total n = 445
	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)
Injection site pain	3 (3.3)	1 (1.1)	1 (1.1)	6 (6.8)	4 (4.4)	15 (3.4)
Injection site reaction	4 (4.4)	2 (2.3)	1 (1.1)	6 (6.8)	6 (6.6)	19 (4.3)
Injury	2 (2.2)	0 (0.0)	0 (0.0)	3 (3.4)	1 (1.1)	6 (1.3)
Diarrhea	2 (2.2)	1 (1.1)	1 (1.1)	0 (0.0)	2 (2.2)	6 (1.3)
Hematoma	2 (2.2)	1 (1.1)	2 (2.2)	1 (1.1)	0 (0.0)	6 (1.3)
Infection viral	4 (4.4)	4 (4.6)	2 (2.2)	2 (2.3)	7 (7.7)	19 (4.3)
Upper respiratory tract infection	2 (2.2)	7 (8.0)	7 (7.7)	3 (3.4)	4 (4.4)	23 (5.2)
Pharyngitis	4 (4.4)	3 (3.4)	3 (3.3)	1 (1.1)	1 (1.1)	12 (2.7)

Group 1 = gD-2t 40 μg, Group 2 = gD-2t 80 μg, Group 3 = gD-2t 20 μg, Group 4 = gD-2t 20 μg, Group 5 = gD-2t 20 μg. N, number of documented doses; n/%, number/% of documented doses with the specified symptom.