HBV vaccination with Fendrix is effective and safe in pre-dialysis CKD population

Abstract

Background: Patients with chronic kidney disease have a poor response to hepatitis B vaccine due to the immunodeficiency conferred from chronic uremia. A recombinant HB vaccine containing an improved adjuvant system AS04 (HBV-AS04) has been manufactured but scarce evidence exists on HBV-AS04 use among patients with CKD. Aim: To assess efficacy and safety of an adjuvanted recombinant vaccine (HBV-AS04) in a large cohort of CKD patients at pre-dialysis stage (with susceptibility to HBV infection). Methods: Patients were prospectively enrolled to receive four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle) at months 1, 2, 3, and 4. Anti-HBs surface antibody concentrations were tested at intervals of 1, 2, 3, 4, and 12 months. Multivariate analyses were performed to assess the parameters, which predicted immunologic response to HBV-AS04 vaccine. Results: One hundred and seven patients were included and 102 completed the study. At completion of vaccine schedule, the frequency of responders (anti-HBs titers ≥ 10 mIU/mL) was 95% (97/102) (mean anti-HBs antibody titers, 688.9 ± 385 mIU/mL), according to per-protocol analysis. Serum haemoglobin levels were greater in responder than non-or low-responder patients to HBV-AS04 (P = 0.04) and this was confirmed by multivariate analysis. The seroprotection rate at month 50 was 88% (30/34) with lower anti-HBs antibody titers (218.5 ± 269.6 mIU/mL, P = 0.001). No major side effects were observed. Conclusions: Our prospective study performed in a real-world setting showed a high immunogenicity and safety of HBV-AS04 vaccine in patients with CKD not yet on maintenance dialysis. Studies provided with longer follow-ups are under way to assess the durability of seroprotection in responders.

Hepatitis B Vaccination in Advanced Chronic Kidney Disease: A Quality Improvement Project at a Veteran Affairs Chronic Kidney Disease Clinic

“…Ahmadi found that there was no significant difference in achieving seroprotection between four doses of a 40 µg compared to three doses of a 20 µg of the Euvax B [ 21 ]. Alternative formulations have also been investigated, including one reviewed by Fabrizi, who looked at the effectiveness of Fendrix, a recombinant HBV vaccine with an improved adjuvant system, and found promising results [ 22 ].…”

Vaccination adjuvated against hepatitis B in Spanish National Healthcare System (SNS) workers typed as non-responders to conventional vaccines

“…Fifteen years after vaccination, the team tested all subjects for antibodies that would protect them from infection and found that the number of antibodies against the virus had fallen since vaccination. The factors associated with a greater likelihood of continuing to present high antibody levels at 15 years were: being male, being older at the time of vaccination and having developed a high number of antibodies at the start [8][9][10][14][15][16][17][18][19][20][21][22][23][24].…”

“…A literature review indicated that the mean percentage of workers who do not respond to the Fendrix Ò vaccine ranges from below 1% to 10% [7,15,19,29,32,35]. This would noticeably affect sample size calculation.…”

Structure–Activity Relationship Studies To Identify Affinity Probes in Bis-aryl Sulfonamides That Prolong Immune Stimuli

“…Compound 20 (11 mg, mmol) was stirred in a solution of 4 N HCl in dioxane for 1 h. The solvent was then removed to obtain compound 21 in quantitative yield as hydrochloride salt (gray solid). 1 N-(4-Chloro-2,5-dimethoxyphenyl)-4-phenoxybenzenesulfonamide (22). Compound 22 was synthesized using 4-chloro-2,5-dimethoxyaniline (2a, 140 mg, 0.74 mmol) and 4-phenoxybenzenesulfonyl chloride (3j, 100 mg, 0.37 mmol) as light yellow solid (51 mg, yield = 33%).…”

“…Similarly, combination adjuvants can be obtained using a PRR or NLR ligand, an immunogenic protein, a delivery system, or another adjuvant with a complementary mechanism of action . One such combination AS04 (adjuvant system 04), consisting of MPLA and alum, has been FDA approved in a hepatitis B vaccine Fendrix and human papillomavirus vaccine Cervarix. − Alternative combinations involving approved adjuvants, TLR agonists, NOD agonists, and delivery systems are being explored. − …”