Efficacy of heat-inactivated hepatitis B vaccine in haemodialysis patients and staff. Double-blind placebo-controlled trial. [Recombinant vaccine and extracting vaccine against hepatitis B in patients with kidney insufficiency: comparative immunogenicity]. Hepatitis B vaccine in patients receiving hemodialysis. Immunogenicity and efficacy. Hepatitis B vaccines in patients with chronic renal failure before dialysis. Comparison of two immunization schedules with recombinant hepatitis B vaccine and natural immunity acquired by hepatitis B infection in dialysis patients. Randomised placebo-controlled trial of hepatitis B surface antigen vaccine in french haemodialysis units: II, Haemodialysis patients. Immunogenicity of recombinant hepatitis B vaccine in dialysis patients.
The efficacy of a heat-inactivated hepatitis B vaccine, 3 micrograms of surface antigen (HBsAg), given at 0, 1, 2, and 5 months, was evaluated in 401 haemodialysis patients in 18 centres by a placebo-controlled, double-blind, randomised trial. The attack-rate of hepatitis B virus (HBV) infections in the control group was 18% over 435 days. The protective efficacy rate of the vaccine was 78% against all HBV infections in the entire study (p = 0.00016), and 94% against HBsAg-positive hepatitis more than 3 months after day 0. Those patients in whom HBV developed showed no evidence of vaccine-acquired anti-HBs. Among 152 similarly randomised staff members receiving three monthly injections, all 5 HBsAg-positive infections occurred in the placebo group (p = 0.022). The vaccine induced anti-HBs in 88% of the patients and 100% of the staff. Immediately after the fourth injection, anti-HBs levels were as high in responding patients as in staff. There were no serious side effects. In the four-dose schedule the vaccine provides dialysis patients with protection of the same order as that given by other hepatitis B vaccines to normal subjects. Patients with chronic renal failure respond rather poorly to hepatitis B vaccines. A better response could be expected from recombinant vaccines including both the S and the pre-S2 antigens. We therefore prospectively compared the immunogenicity of plasma-derived Hevac B vaccine (H) with that of recombinant GenHevac B vaccine (G).
                Vaccinations were performed in 120 non-dialyzed patients with chronic renal failure. The patients were randomly divided into two groups. Group G included 60 patients (24 males, mean age 58 +/- 16 years, mean creatinine clearance 25.3 +/- 12.6 ml/min) who were given the Hevac B vaccine at the dose of 5 micrograms. Group H included 60 patients (31 males, mean age 60 +/- 15 years, mean creatinine clearance 24.4 +/- 11.1 ml/min) who were given GenHevac B vaccine at the dose of 20 micrograms. All vaccinations were repeated at 0, 1, 2, 4 and 12 months.
                Following the fourth injection, seroconversion (anti-Hbs > or = 2 mlU/ml) was observed in 50/59 (85%) of the patients in group G versus 38/58 (67%) in group H (p < 0.02). Seroprotection (> or = 10 mlU/ml) was obtained in 42/59 (71%) vs 34/58 (59%), (NS) in the two groups respectively with a geometric mean titer of 112 versus 229 mlU/ml (NS) in responders. Following the booster injection at the 12th month, seroconversion was achieved in 48/51 (94%) vs 40/53 (76%) (p < 0.01) and seroprotection in 84% vs 70% (p = 0.053) respectively. The mean geometric titers were 879 and 1001 mlU/ml.
                Recombinant GenHevac B vaccine elicits seroconversion and seroprotection in a higher proportion of patients with chronic renal failure than the plasma-derived Hevac B vaccine, with comparably high antibody titers in responders. Therefore, GenHevac B vaccine should be recommended for vaccinating patients with chronic renal failure against hepatitis B. We evaluated the immunogenicity and efficacy of hepatitis B vaccine (Heptavax-B) in a randomized, double-blind, placebo-controlled trial involving 1311 patients receiving hemodialysis in the United States. After three doses of vaccine (40 micrograms each) had been administered, 63 per cent of the patients were antibody-positive. After correction for possible passive transfer of antibodies by blood transfusion, only 50 per cent of vaccine recipients were considered vaccine responders. The incidence of hepatitis B viral infection during the 25 months of the trial was much lower than had been anticipated and was virtually the same in the vaccine and placebo recipients (6.4 and 5.4 per cent, respectively). Four cases of hepatitis B occurred in patients who had an apparent antibody response to the vaccine, but in each case either antibody had reached low or undetectable levels before hepatitis B surface antigen was detected or the patient had been receiving immunosuppressive therapy. This study did not demonstrate the efficacy of the vaccine in a population of patients receiving dialysis in whom both the rate of antibody response to hepatitis B vaccine and the viral attack rate were low. Other measures to control transmission of hepatitis B virus in dialysis units, including surveillance for hepatitis B surface antigen and isolation of patients who are positive for the antigen, must be continued. Hepatitis B remains a significant risk to patients receiving chronic hemodialysis, but no certain method of prevention has been identified. We tested two vaccines, plasma-derived vaccine (40-micrograms dose) and recombinant-derived vaccine (40-micrograms and 20-micrograms doses), in 61 patients with chronic renal failure who were not yet dependent on dialysis. Patients were followed up clinically and with laboratory tests of kidney function and hepatitis B virus serology for one year. Significantly more recipients of plasma-derived vaccine responded to vaccination; they also achieved a higher titer of antibody to hepatitis B virus than did recipients of recombinant-derived vaccine when evaluated at 6, 7, 9, and 12 mo after vaccination. No serious side effects were observed with any vaccine preparation, nor were excessive adverse effects observed in any group. Compared with the dialysis patients previously studied, patients with renal failure who were not yet dependent on dialysis responded more favorably to the hepatitis B virus vaccine. In a prospective study over a 2-year period we compared two practical dosage schedules to vaccinate dialysis patients against hepatitis B virus (HBV) infection using a yeast-derived recombinant hepatitis B vaccine (Engerix-B). In addition, the natural history of this acquired immunity was compared with that developed through HBV infection in dialysis patients and healthy subjects. Patients on dialysis treatment (haemo or peritoneal) who were tested to be negative for hepatitis B surface antigen (HBsAg), anti-HBs and anti-HB core were allocated at random to receive HB vaccine according to one of the two schedules. The two groups receiving the vaccine were matched for age, sex, mean duration on dialysis and the form of dialysis treatment received. The group of patients who received a four-dose schedule (at 0, 1, 2 and 6 months) of 40 micrograms of HB vaccine each time (group 2) achieved a seroconversion rate of 79% 1 month after the last dose (at month 7) compared with a seroconversion rate of 55% in those who received three doses (at 0, 1 and 6 months) of 40 micrograms each (group 1). Healthy controls who received half the amount of vaccine on a three-dose schedule (group 3) attained 100% seroconversion (p < 0.05). When retested at 24 months, 30% of seroconverters in group 1 had lost their protective immunity, compared with only 6% in group 2 and 15% in group 3. The magnitude of antibody response (total and anti-(a)-specific) was assessed in the vaccinees at 24 months and compared with that of two other control groups, dialysis patients (group 4) and healthy volunteers (group 5), who had acquired immunity from HBV infection. In general, the total and anti-(a)-specific HBs titres in the dialysis patients (groups 1, 2 and 4) were lower than in their corresponding healthy controls (groups 3 and 5), irrespective of whether the protective immunity was acquired by vaccination or HBV infection. However, the anti-HBs titres in dialysis patients who received four doses were significantly higher than in those who received only three doses (p < 0.05), which indicated a better protective immunity in favour of the former regime. The magnitude of antibody response in the vaccinees of groups 2 and 3 compared well with their respective controls, groups 4 and 5, who had acquired their immunity through HBV infection. This implied that the yeast-derived vaccine was sufficiently immunogenic and provided lasting protection in patients and healthy subjects vaccinated by an appropriate dosage schedule.(ABSTRACT TRUNCATED AT 400 WORDS) A vaccine against hepatitis B surface antigen (Institut Pasteur Production) was assessed in 138 haemodialysis patients in a placebo-controlled randomised double-blind trial. In an interim analysis, hepatitis B infections were observed in 21% of the vaccine group and 45% of the placebo group (p less than 0.02). 2 of the infections in the vaccine group and 12 of the infections in the placebo group occurred after the third injection. 60% of the vaccine recipients had an immune response. 4 months after the first injection the mean titre of anti-HBs was 120 mlU/ml. Eighty-eight dialysis patients were vaccinated with recombinant hepatitis B vaccine prepared in yeast. Fourty-nine patients were immunized 3 times (months 0, 1, 6) intragluteally with 40 micrograms hepatitis B surface antigen (HBsAg) per dose. Only 32 of them (65.3%) showed anti-HBs concentrations above 10 IU/l with a geometric mean titer (GMT) of 180.7 IU/l after 3 vaccinations, whereas all of the 16 healthy controls, vaccinated 3 times with a 10-micrograms dose of the same vaccine batch, had specific antibodies higher than 10 IU/l (GMT 897.4 IU/l). Responses of patients were slightly higher than those of dialysis patients vaccinated in an earlier study with plasma-derived vaccine according to the same schedule. Results in 20 patients immunized 6 times intragluteally with 40 micrograms HBsAg/dose in monthly intervals were not better (at month 7, 65% showed anti-HBs concentrations greater than 10 IU/l; GMT = 126.6 IU/l), and 19 patients receiving 6 times 20 micrograms HBsAg monthly showed significantly lower responses (anti-HBs greater than 10 IU/l in 42% of vaccinees, GMT = 89.5 IU/l). The vaccine was tolerated well; side-effects were slight, and no serious adverse reactions were observed. In conclusion, recombinant hepatitis B vaccine is comparable to plasma-derived vaccine also in the case of dialysis patients; a 6-dose schedule does not seem to have much advantage compared to the conventional 3-dose regimen.
Plasma derived vaccines are more effective than placebo in achieving hepatitis B antibodies, while no statistically significant difference was found between recombinant and plasma vaccines. No statistically significant difference of effectiveness was observed between a reinforced vaccination series versus routine vaccinations of three inoculations of recombinant vaccine.