Immunogenicity of an investigational hepatitis B vaccine (hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide) in nonresponders to licensed hepatitis B vaccine

Figures & data

Table 1. Participant characteristics

Characteristic	Primary study		Substudy
	HBsAg-1018 (n = 19)	HBsAg-Eng (n = 16)	HBsAg-1018 (n = 11)	HBsAg-Eng (n = 13)
Age in years; mean (range)	42.9 (27–60)	42.4 (28–59)	40.9 (18–57)	42.7 (19–58)
Gender female; n (%)	3 (15.8)	1 (6.2)	8 (72.7)	7 (53.8)
Male; n (%)	16 (84.2)	15 (93.8)	3 (27.3)	6 (46.2)
Race Caucasian; n (%)	19 (100)	16 (100)	10 (90.9)	12 (92.3)
Black; n (%)	0 (0)	0 (0)	1 (9.1)	1 (7.7)
Weight in kilograms (range)	86.7 (63.6–126)	90.1 (54.5–106.8)	81.3 (56.8–118.1)	85 (53.6–131.8)
Height in centimeters (range)	174.6 (152.4–188)	175.9 (168–187)	171.6 (162.5–189)	168.7 (156.2–182.8)
Current smoker; n (%)	1 (5.3)	5 (31.3)	5 (45.5)	3 (23.1)

Table 2. Antibody response following vaccination with HBsAg-1018 or HBsAg-Eng in nonresponders to HBV

Parameter	Time measured	Nonresponders to 3 doses (primary study)		Nonresponders to 4 to 6 Doses (substudy)
		HBsAg-1018	HBsAg-Eng	HBsAg-1018	HBsAg-Eng
% Anti-HBs ≥ 10 mIU/mL	Week 4	10/19 (52.6)	6/16 (37.5)	7/11 (63.6)	7/12 (58.3)
	Week 26^a	8/9 (88.9)	4/6 (66.7)	4/7 (57.1)	3/7 (42.9)
	Week 52^a	5/10 (50.0)	1/6 (16.7)	4/7 (57.1)	0/7 (0)
% Anti-HBs ≥ 100 mIU/mL	Week 4	4/19 (21.1)	2/16 (12.5)	6/11 (54.5)*	1/12 (8.3)
	Week 26^a	0/9 (0)	1/6 (16.7)	0/7 (0)	0/7 (0)
	Week 52^a	1/10 (10.0)	0/6 (0)	0/7 (0)	0/7 (0)
Geometric Mean Antibody Concentration (GMC)	Day 0	1.00 (n = 19)	1.05 (n = 16)	1.00 (n = 11)	1.00 (n = 12)
	Week 4 all	14.7 (n = 19)	5.33 (n = 16)	34.8 (n = 11)	11.2 (n = 12)
	Week 4 responders	90.0 (n = 10)	41.1 (n = 6)	264.0 (n = 7)**	46.5 (n = 7)
	Week 26 responders	20.3 (n = 9)	14.2 (n = 6)	14.8 (n = 7)	3.22 (n = 7)
	Week 52 responders	12.7 (n = 10)	1.96 (n = 6)	6.99 (n = 7)***	1.21 (n = 7)

^a Participants with anti-HBs levels ≥ 10mIU/mL at week 4; *p = 0.027; **p = 0.021; ***p = 0.030

Table 3. Immunogenicity and adverse events reported after immunization with second and third doses of HBsAg-Eng in nonresponders to HBsAg-ISS or HBsAg-Eng in the primary study

Measurement	Second HBsAg-Eng dose in nonresponders to		Third HBsAg-Eng dose in nonresponders to
	HBsAg-1018 (n = 5)	HBsAg-Eng (n = 8)	HBsAg-1018 (n = 4)	HBsAg-Eng (n = 7)
Immunogenicity
n (%) anti-HBs ≥ 10 mIU/mL	-	-	3 (75.0)	2 (28.6)
n (%) anti-HBs ≥ 100 mIU/mL	-	-	1 (25.0)	1 (14.3)
GMC	-	-	5.2 (0.5–56.6)	75.7 (0.7–8781)
Injection site
Redness	0 (0)	0 (0)	0 (0)	0 (0)
Swelling	0 (0)	0 (0)	0 (0)	0 (0)
Site warmth	1 (20)	0 (0)	0 (0)	0 (0)
Tenderness	1 (20)	2 (25)	3 (75)	1 (14.3)
Pain with arm movement	2 (40)	2 (25)	2 (50)	1 (14.3)
Systemic
Fever	0 (0)	1 (14.3)	0 (0)	0 (0)
Headache	1 (20)	2 (25)	0 (0)	2 (28.6)
Muscle ache	0 (0)	1 (12.5)	0 (0)	0 (0)
Fatigue	1 (20)	1 (12.5)	0 (0)	1 (14.3)
Nausea	0 (0)	1 (12.5)	0 (0)	1 (14.3)
Vomiting	0 (0)	0 (0)	0 (0)	0 (0)
Diarrhea	1 (20)	0 (0)	0 (0)	1 (14.3)

Table 4. Adverse events reported after immunization with HBsAg-1018 or HBsAg-Eng

Adverse event	Nonresponders to 3 doses (primary study)		Nonresponders to 4 to 6 doses (substudy)
	HBsAg-1018 (n = 19)	HBsAg-Eng (n = 16)	HBsAg-1018 (n = 11)	HBsAg-Eng (n = 13)
Injection site
Redness	0 (0)	0 (0)	0 (0)	1 (7.7)
Swelling	0 (0)	0 (0)	0 (0)	0 (0)
Site warmth	2 (10.5)	1 (6.3)	1 (9.1)	2 (15.4)
Tenderness	12 (63.2)*	3 (18.8)	9 (81.8)**	2 (15.4)
Pain with arm movement	7 (36.8)	3 (18.8)	6 (54.5)	3 (23.1)
Systemic
Fever	0 (0)	0 (0)	0 (0)	1 (7.7)
Headache	1 (5.3)	4 (25)	3 (27.3)	7 (53.8)
Muscle ache	2 (10.5)	1 (6.3)	3 (27.3)	3 (23.1)
Fatigue	2 (10.5)	3 (18.8)	4 (36.4)	3 (23.1)
Nausea	0 (0)	2 (12.5)	1 (9.1)	0 (0)
Vomiting	0 (0)	0 (0)	0 (0)	0 (0)
Diarrhea	1 (5.3)	1 (6.3)	2 (18.2)	1 (7.7)

* p = 0.016; **p = 0.003