anti-HBs Response Research Articles

Anti-preS responses influence the anti-HBs response in newborns after vaccination with the third generation Sci-B-Vac™ vaccine

We analysed the specificity and significance of the antibody response towards the linear preS1 sequence that has been shown to represent the “hepatocyte binding site” comprising amino acids preS1 (21–47) or the specific preS2 (131–140) antibody response to the “polymerised albumin receptor” in relation to the antibody response to hepatitis B surface antigen during immunisation of healthy children with the preS-containing Sci-B-Vac™ vaccine. Twenty-eight healthy newborns received three doses of the Sci-B-Vac™ vaccine according to a 0-, 1-, and 6-month scheme. Seventeen (61%) of the 28 newborns had detectable levels of anti-preS1 (21–47) antibodies and 14 (50%) were anti-preS2 (131–140) reactive at 6 and/or 9 months after initiation of the vaccination. The mean levels of anti-HBs were significantly higher in the anti-preS2 (131–140) non-reactive (24 580 ± 7815 IU/l, mean + SEM) compared with the reactive sera (7287 ± 2317 IU/l, p < 0.025). The highest anti-HBs levels were found in newborns who exhibited reactivity towards the aa 21–47 of the preS1 but lacked anti-preS2 (131–140) reactivity.

Biological significance of amino acid substitutions in hepatitis B surface antigen (HBsAg) for glycosylation, secretion, antigenicity and immunogenicity of HBsAg and hepatitis B virus replication

Amino acid substitutions of hepatitis B surface antigen (HBsAg) may affect the antigenicity and immunogenicity of HBsAg, leading to immune escape and diagnostic failure. The amino acid positions 122 and 160 are known as determinants for HBsAg subtypes d/y and w/r, respectively. The substitution K122I has been shown to strongly affect HBsAg antigenicity. In this study, we investigated the significance of naturally occurring amino acid substitutions K122I, T123N, A159G and K160N. Both T123N and K160N substitutions resulted in additional N-glycosylated forms of HBsAg, while the other mutations produced more glycosylated HBsAg compared with the wild type (wt). Detection of HBsAg by ELISA and immunofluorescence staining indicated that variant HBsAg (vtHBsAg) with K122I was not recognized by HBsAg immunoassays, while vtHBsAg with T123N, A159G, K160N and A159G/K160N had reduced antigenicity. DNA immunization in BALB/c mice revealed that wtHBsAg and vtHBsAg with T123N and K160N are able to induce antibodies to HBsAg (anti-HBs), whereas K122I and A159G greatly impair the ability of HBsAg to trigger anti-HBs responses. The cellular immune response to the HBsAg aa 29-38 epitope was enhanced by the K160N substitution. Using replication competent clones of hepatitis B virus (HBV), T123N and A159G substitutions were shown to strongly reduce virion assembly. The amino acid substitution K160N appeared to compensate for the negative effect of A159G on virion production. These results reveal complex effects of amino acid substitutions on biochemical properties of HBsAg, on antigenicity and immunogenicity, and on the replication of HBV.

Randomized Controlled Study Investigating Viral Suppression and Serological Response following Pre-S1/Pre-S2/S Vaccine Therapy Combined with Lamivudine Treatment in HBeAg-Positive Patients with Chronic Hepatitis B

The aim of the current study was to evaluate viral suppression following combined treatment with an S/pre-S1/pre-S2 vaccine and lamivudine in patients with chronic hepatitis B. We established a randomized, controlled clinical trial to compare the responses of three different treatment groups: those receiving vaccine monotherapy, lamivudine monotherapy, or combination treatment. Viral response was evaluated via hepatitis B virus (HBV) DNA suppression using different levels of classification. Seroconversion was evaluated via HBeAg loss, HBeAg seroconversion, HBsAg loss, and anti-HBs response. We found that the group receiving combination treatment demonstrated a significant increase in viral suppression over that for the lamivudine or vaccine monotherapy group, although the HBeAg seroconversion rate was not different. This enhanced suppression effect in the combination group was reversed after the discontinuation of vaccine treatment, suggesting that booster doses are required for a sustained viral response. Anti-HBs was detected in 55/120 vaccine recipients, but only 3 patients demonstrated HBsAg loss, indicating that the vaccine-induced anti-HBs was unable to completely neutralize HBsAg in the serum. At the study end point, anti-HBs responders showed significantly higher HBeAg seroconversion rates, greater suppression of HBV DNA levels, and a lower median reduction in HBV DNA levels than those of anti-HBs nonresponders. Our results suggest that combined treatment with the vaccine and lamivudine was significantly more effective than lamivudine monotherapy in the short term and was especially successful in producing viral suppression and an enhanced anti-HBs antibody response.

Antibody response following hepatitis B vaccination in dialysis patients: Does depression and life quality matter?

Previously, it was demonstrated that antibody production against hepatitis B virus (HBV) surface antigen (anti-HBs) achieved in hemodialysis patients is suboptimal. Decreased health-related quality of life (HRQOL) and depression is common among hemodialysis patients. This study evaluated whether HRQOL and depressive behavior are associated with antibody response against HBV surface antigen in hemodialysis patients. Depressive symptoms and HRQOL were assessed by Beck Depression Inventory (BDI) and Medical Outcomes Study Short Form (SF-36), respectively. Patients were separated into non-seroconversion (anti-HBs antibody titers <10 IU/L) and seroconversion (anti-HBs antibody titers ≥10 IU/L) groups. Among 188 patients, 37 (19.7%) were diagnosed as nonresponsive to vaccination (anti-HBs antibody titers <10 1U/L). Anti-HBs response is positively associated with Physical Component Summary Score of SF-36 (odds ratio: 1.44; P: 0.009) and albumin (odds ratio: 10.615, P: 0.007), and negatively with BDI score (odds ratio: 0.903, P: 0.007). We concluded that HRQOL and depression is closely related with antibody response following HBV vaccine in hemodialysis patients.

Evaluation of RTS,S/AS02A and RTS,S/AS01B in Adults in a High Malaria Transmission Area

BackgroundThis study advances the clinical development of the RTS,S/AS01B candidate malaria vaccine to malaria endemic populations. As a primary objective it compares the safety and reactogenicity of RTS,S/AS01B to the more extensively evaluated RTS,S/AS02A vaccine.MethodologyA Phase IIb, single centre, double-blind, controlled trial of 6 months duration with a subsequent 6 month single-blind follow-up conducted in Kisumu West District, Kenya between August 2005 and August 2006. 255 healthy adults aged 18 to 35 years were randomized (1∶1∶1) to receive 3 doses of RTS,S/AS02A, RTS,S/AS01B or rabies vaccine (Rabipur®; Chiron Behring GmbH) at months 0, 1, 2. The primary objective was the occurrence of severe (grade 3) solicited or unsolicited general (i.e. systemic) adverse events (AEs) during 7 days follow up after each vaccination.Principal FindingsBoth candidate vaccines had a good safety profile and were well tolerated. One grade 3 systemic AE occurred within 7 days of vaccination (RTS,S/AS01B group). No unsolicited AEs or SAEs were related to vaccine. A marked increase in anti-CS antibody GMTs was observed post Dose 2 of both RTS,S/AS01B (31.6 EU/mL [95% CI: 23.9 to 41.6]) and RTS,S/AS02A (16.7 EU/mL [95% CI: 12.9 to 21.7]). A further increase was observed post Dose 3 in both the RTS,S/AS01B (41.4 EU/mL [95% CI: 31.7 to 54.2]) and RTS,S/AS02A (21.4 EU/mL [95% CI: 16.0 to 28.7]) groups. Anti-CS antibody GMTs were significantly greater with RTS,S/AS01B compared to RTS,S/AS02A at all time points post Dose 2 and Dose 3. Both candidate vaccines produced strong anti-HBs responses. Vaccine efficacy in the RTS,S/AS01B group was 29.5% (95% CI: −15.4 to 56.9, p = 0.164) and in the RTS,S/AS02A group 31.7% (95% CI: −11.6 to 58.2, p = 0.128).ConclusionsBoth candidate malaria vaccines were well tolerated over a 12 month surveillance period. A more favorable immunogenicity profile was observed with RTS,S/AS01B than with RTS,S/AS02A. Trial RegistrationClinicaltrials.gov NCT00197054

Modulation of the immune response to HBV vaccination by hemodialysis membranes

Seroconversion response to Hepatitis B virus (HBV) vaccination is limited in uremic patients because of impaired humoral and cellular immune activity. Recent studies show that high-flux (HF) hemodialysis (HD) membranes can improve T cell functions and decrease the proinflammatory cytokine activation more effectively than low-flux (LF) membranes. In regard to HF membranes may have immune modulator effects; we compared the antibody responses to hepatitis B vaccination between HF HD and LF HD membranes. One thousand four hundred and eight patients on HD programmed for 4 h three times a week at three different centers with HF or LF membranes were scanned. Anti-HBs levels of these patients who were vaccinated with recombinant DNA HBV vaccine on the 0, 1st, 2nd and 6th month from the beginning were recorded on the 0, 3rd, 6th, 9th and 12th month of vaccination schedule. Seroconversion rate was 84.2% in HF group and 52.7% in LF group on the 6th month (P < 0.01). Ratio of the patients who had >100 IU/l antibody titers in HF group was 22.8%, while it was 10.9% in LF group (P < 0.01). Also on the 9th, 12th and 24th month; seroconversion rates in HF group were higher than LF group: 91.1-70.9% (P < 0.05), 95.0-81.8% (P < 0.05), 92.1-83.7% (P > 0.05), respectively. Ratio of the patients who did not show any seroconversion was higher in LF group than HF group; on the 6th month as 15.8-47.3% (P < 0.001), on the 9th month 8.9-29.1% (P < 0.05), on the 12th month as 5.0-18.2% (P < 0.05), and on the 24th month as 7.9-16.4% (P > 0.05), respectively. We showed that ratio of anti-HBs seroconversion response to hepatitis B vaccination in patients receiving HD with HF membranes was higher than LF membranes. This finding suggests that HF membranes may improve immune modulator effects.

Protective Anti-Hepatitis B Virus Responses in Rhesus Monkeys Primed with a Vectored Measles Virus and Boosted with a Single Dose of Hepatitis B Surface Antigen

The widely used hepatitis B virus (HBV) vaccine is based on three doses of hepatitis B surface antigen (HBsAg) protein. We previously showed that vectored measles viruses (MV) expressing HBsAg retain measles vaccine function in monkeys but do not induce a protective anti-HBs response in all animals. We show here that a single dose of HBsAg protein following a three-dose vaccination regimen with an optimized HBsAg-expressing MV elicits protective anti-HBs responses in all four vaccinated Rhesus monkeys. Vaccination strategies coupling the effective, long-term immunity elicited by the high-coverage MV vaccine to prophylactic HBV immunity are discussed.

The immunization effects of HBV core antigen and surface antigen fusion protein in mice

To evaluate the immunization effects of HBV core antigen and surface antigen fusion protein. The DNA fragments encoding HBsAg 100-162 aa; HBcAg 1-78 aa and HBcAg 83-144 aa were PCR-amplified, and then cloned into pcDNA3 plasmid. The chimeric gene was subcloned into the prokaryotic vector, pRSET-B. The E.coli expressed recombinant protein purified. BALB/c mice were immunized with recombinant protein or eukaryotic expression plasmid, humoral response and cellular response were examined. The plasmid containing the chimeric gene of HBsAg and HBcAg induced effective anti-HBs antibody response and strong HBcAg specific lymphocyte proliferative response, but could not induce anti-HBc antibody response. Fusion protein induced strong anti-HBs and anti-HBc antibody response, and it also caused significant HBcAg specific lymphocyte proliferation. Compared to the recombinant fusion protein, the plasmid containing the chimeric gene of HBsAg and HBcAg can induce more effective cellular response but weaker humoral response. Compared to the recombinant fusion protein, the plasmid containing the chimeric gene of HBsAg and HBcAg is a more effective vaccine.

PreS1 epitope recognition in newborns after vaccination with the third-generation Sci-B-Vac™ vaccine and their relation to the antibody response to hepatitis B surface antigen

BackgroundSci-B-Vac™ is a recombinant, hepatitis B vaccine derived from a mammalian cell line and containing hepatitis B surface antigen (HBsAg) as well as preS1 and preS2 antigens. Few studies have been performed on the antibody responses to preS1 in relation to the antibody to hepatitis B surface antigen (anti-HBs) response during immunisation of healthy children with preS-containing vaccines.ResultsIn this study 28 healthy newborns were randomly selected to receive either 2.5 ug or 5.0 ug of the Sci-B-Vac vaccine. Children received three doses of vaccine according to a 0-, 1-, 6-month scheme. Antibodies against the S-protein and three synthetic peptides mimicking three B-cell preS1 epitopes, (21–32 amino acid epitope), (32–47 amino acid epitope) and the C-terminal (amino acid epitope 94–117) were determined at 6 and 9 months. Fourteen (50%) of the 28 newborns had detectable levels of anti-preS1 (21–32) antibodies; 15 (54%) were anti-preS1 (32–47) reactive and 12 (43%) were anti-preS1 (94–117) reactive at 6 or 9 months after initiation of the vaccination. Significantly higher levels of anti-HBs were observed in the sera of patients with detectable anti-preS1 (32–47) reactivity (24 550 ± 7375 IU/L, mean ± SEM) as compared with the non-reactive sera (5991 ± 1530 IU/L, p < 0.05). The anti-HBs levels were significantly lower if none (p < 0.05) or one (p < 0.025) of the preS1 (21–32, 32–47, 94–117) peptides were recognised compared with the anti-HBs levels if two or three peptides were recognised.ConclusionRecognition of several preS1 epitopes, and in particular, the epitope contained within the second half of the hepatocyte binding site localised in the hepatitis B surface protein of the third-generation hepatitis B vaccine is accompanied by a more pronounced antibody response to the S-gene-derived protein in healthy newborns.

Investigation (In Vivo and In Vitro) of Booster Dose Vaccine Requirement for Long-Term Protection against Hepatitis B Virus Infection

Aim: Studies have shown that no booster dose was required at least 10 to 15 years after a primary vaccination for individuals who developed protective anti-hepatitis B surface (anti-HBs) antibodies. In this study, booster dose requirement for HBV after primary immunization was investigated. Materials and Methods: Seventeen individuals vaccinated previously were enrolled in the study. They had once developed a protective level of anti-HBs antibody after immunization and their anti-HBs titer had declined to an underprotective level. Twenty uninfected and unvaccinated healthy people were chosen as controls. Lymphoproliferative response to in-vitro stimulation with hepatitis B surface antigen (HBsAg) and anti-HBs response to vaccine were evaluated for immune response. Results: T lymphocytes from 4 (24%) of the study group showed lymphoproliferative response to HBsAg stimulation while none of the controls did (P < 0.05). In all subjects in the study group, anti-HBs response (>= 10 mIU/ml) was detected 1 to 7 days after the booster injection but in only 2 of the controls antibody response was detected 28 days after the first dose of HBV vaccine (P < 0.0001). Conclusions: A booster dose of HBV vaccine might not be required because of immunological memory.

Hepatitis B vaccination of haemodialysis patients: randomized controlled trial comparing plasma-derived vaccine with and without pre-S2 antigen

The pre-S2 protein of the hepatitis B virus envelope evokes anti-pre-S2 antibodies and enhances the anti-HBs response after vaccination in mice. In order to evaluate the immunogenicity of the pre-S2 Ag in man, 102 HBsAg, anti-HBs, anti-HBc-negative haemodialysis patients were vaccinated at random according to one of four vaccination schedules: 5 micrograms plasma vaccine Pasteur (containing 1% pre-S2) or 20 micrograms plasma vaccine MSD (no pre-S2) at 0, 1, 2, 4, 6 and 12 months; or 10 micrograms Pasteur or 40 micrograms MSD at 0, 1, 2 and 6 months. Anti-HBs levels were measured by RIA and expressed in IU l-1; anti-pre-S2 response was evaluated by both EIA and Western blot analysis. Eighty-four per cent (95% confidence interval: 75-93) of the patients exhibited an anti-HBs response of 2 IU l-1 or more and 71% (95% confidence interval: 61-81) reached an anti-HBs level of at least 10 IU l-1 within 13 months of the start of vaccination. Anti-HBs response correlated with age (the response rate decreased with increasing age) but not with either the type of vaccine or dosage. An anti-pre-S2 response was observed in 16% (EIA) and 46% (Western blot) of the patients immunized with the Pasteur vaccine and none (EIA, Western blot) of the MSD group. The level of anti-pre-S2 antibodies correlated with high anti-HBs titres; an anti-pre-S2 response occurred in only one anti-HBs-negative patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Safety and immunogenicity of a combined hepatitis B virus-Haemophilus influenzae type B vaccine comprising a synthetic antigen in healthy adults

The combined HB-Hib vaccine candidate Hebervac HB-Hib® (CIGB, La Habana), comprising recombinant HBsAg and tetanus toxoid conjugate synthetic PRP antigens has shown to be highly immunogenic in animal models. A phase I open, controlled, randomized clinical trial was carried out to assess the safety and immunogenicity profile of this bivalent vaccine in 25 healthy adults who were positive for antibody to HBsAg (anti-HBs). The trial was performed according to Good Clinical Practices and Guidelines. Volunteers were randomly allocated to receive the combined vaccine or simultaneous administration of HB vaccine Heberbiovac-HB® and Hib vaccine QuimiHib® (CIGB, La Habana). All individuals were intramuscularly immunized with a unique dose of 10 µg HBsAg plus 10 µg conjugated synthetic PRP. Adverse events were actively recorded after vaccine administration. Total anti-HBs and IgG anti-PRP antibody titers were evaluated using commercial ELISA kits at baseline and 30 days post-vaccination. The combined vaccine candidate was safe and well tolerated. The most common adverse reactions were local pain, febricula, fever and local erythema. These reactions were all mild in intensity and resolved without medical treatment. Adverse events were mostly reported during the first 6 - 72 hours post-vaccination. There were no serious adverse events during the study. No severe or unexpected events were either recorded during the trial. The combined vaccine elicited an anti-HBs and anti-PRP booster response in 100% of subjects at day 30 of the immunization schedule. Anti-HBs and anti-PRP antibody levels had at least a two-fold increase compared to baseline sera. Even more, anti-HBs antibody titer showed a four-fold increase in 100% of volunteers in the study group. The results indicate that the combined HB-Hib vaccine produces increased antibody levels in healthy adults who have previously been exposed to these two antigens. To our knowledge, this is the first demonstration of safety and immunogenicity for a combined vaccine comprising recombinant HBV and synthetic Hib antigens. The present results support phase I-II clinical trial in the target population, two months old healthy infants.

Low dose revaccination induces robust protective anti-HBs antibody response in the majority of healthy non-responder neonates

A sizeable proportion (1-10%) of healthy adults and to lesser extent neonates vaccinated with triple 10 microg hepatitis B (HB) vaccine fail to mount a protective antibody response. Revaccination with the same vaccine dose has proved to be effective in a significant number of primary non-responders. The influence of revaccination with lower vaccine doses however has not been studied adequately in non-responder neonates. This study was conducted to evaluate the influence of supplementary vaccination with a single low and standard dose of a recombinant hepatitis B (HB) vaccine in healthy Iranian non-responder neonates to primary vaccination. Iranian neonates unable to respond to primary vaccination with 10, 5 or 2.5 microg doses of recombinant HB vaccine were revaccinated with a single additional dose of the same concentration. Serum anti-HBs antibody titer was measured by sandwich ELISA. Administration of a single additional dose induced seroprotection (anti-HBs> or =10IU/L) in 10/12 (83%), 10/12 (83%) and 21/24 (87.5%) of non-responder neonates in 10, 5 and 2.5 microg vaccine recipients with geometric mean titers (and 95% confidence limits) of 1358 (258-7142), 401 (79-2038) and 164 (62-433) IU/L, respectively. The log-transformed antibody titer obtained for the 10 microg dose recipients was significantly higher than that of the 2.5 microg dose vaccinees (p=0.028). No significant differences in anti-HBs titer were observed between other groups of vaccinees. However, the total seroprotection rates obtained after administration of four low doses of 2.5 and 5 microg were significantly higher than that obtained after administration of the classical three 10 microg doses (p=0.029 and p=0.006, respectively). The total seroprotection rates were similar between all groups of vaccines receiving four doses of 2.5, 5 and 10 microg vaccine doses. These results indicate that a significant proportion of non-responder neonates can be induced to develop a protective anti-HBs response following revaccination with a single low dose vaccine. Thus adaptation of four low dose (2.5 or 5 microg) vaccination is expected to induce higher seroprotection rate and lower or comparable anti-HBs antibody titer in healthy neonates.

Long-term protection against HBV chronic carriage of Gambian adolescents vaccinated in infancy and immune response in HBV booster trial in adolescence.

BackgroundChronic infection with hepatitis B virus (HBV) arising in childhood is associated with hepatocellular carcinoma in adult life. Between 1986 and 1990, approximately 120,000 Gambian newborns were enrolled in a randomised controlled trial to assess the effectiveness of infant HBV vaccination on the prevention of hepatocellular carcinoma in adulthood. These children are now in adolescence and approaching adulthood, when the onset of sexual activity may challenge their hepatitis B immunity. Thus a booster dose in adolescence could be important to maintain long-term protection.MethodsFifteen years after the start of the HBV infant vaccination study, 492 vaccinated and 424 unvaccinated children were identified to determine vaccine efficacy against infection and carriage in adolescence. At the same time, 297 of the 492 infant-vaccinated subjects were randomly offered a booster dose of HBV vaccine. Anti-HBs was measured before the booster, and two weeks and 1 year afterwards (ISRCTN71271385).ResultsVaccine efficacy 15 years after vaccination was 67.0% against infection as manifest by anti-HBc positivity (95% CI 58.2–74.6%), and 96.6% against HBsAg carriage (95% CI 91.5–100%). 31.2% of participants had detectable anti-HBs with a GMC of 32 IU/l. For 168 boosted participants GMC anti-HBs responses were 38 IU/l prior to vaccination, 524 IU/l two weeks after boosting, and 101 IU/l after 1 year.ConclusionsHBV vaccination in infants confers very good protection against carriage up to 15 years of age, although a large proportion of vaccinated subjects did not have detectable anti-HBs at this age. The response to boosting persisted for at least a year.Trial RegistrationControlled-Trials.com ISRCTN71271385

Characteristic of immune response of hepatitis B immunization on infants with two different schedules

Hepatitis B immunization gives protection to hepatitis B disease. The purpose of this study was to assess the immune response of hepatitis B immunization on infants with 0,2,9 and 3,4,9 months of age schedule. The study was performed cross sectionally at the Child Health clinic of Social Pediatric sub division H. Adam Malik Hospital from November 1st 1998 until February 28th 1999. The anti HBs responses were examined in blood by ELISA method one month after the third immunization at the Clinical Pathology Division FK-USU/H. Adam Malik Hospital. Protective immune response defined if the anti HBs level ³ 10 mIU/ml. Nutritional status of infants were grouped according to the NCHS classification. The result obtained were statistically tested by Fisher exact test and t-test, on the level of significance p &lt; 0.05. Twenty six (86.7%) of the infants had protective immune response and there were no significant difference on the level of immune response among these two groups. Gender and nutritional status seems to have no influence on the anti HBs level. In Conclusion, hepatitis B immunization either with 0,2,9 or 3,4,9 months of age schedule obtained the same immune response.

Extended double-dosage HBV vaccination after liver transplantation is ineffective, in the absence of lamivudine and prior wash-out of human Hepatitis B immunoglobulins

Background The recommended prophylaxis against hepatitis B virus recurrence after liver transplantation based on hepatitis B immunoglobulins and lamivudine is highly expensive. A recent study reported a significant anti-HBs (antibodies against hepatitis B surface antigen) response after a reinforced vaccination against hepatitis B virus, a result not confirmed in a study from our group. Concomitant lamivudine treatment and the achievement of complete washout of anti-hepatitis B-specific immunoglobulin prior to vaccination in our study could explain the contradiction. Aims To test the efficacy of a reinforced anti-hepatitis B virus vaccination schedule without lamivudine and without previous anti-hepatitis B-specific immunoglobulin washout. Methods A double reinforced course of S-recombinant hepatitis B virus vaccination was given to seven male patients who were transplanted for hepatitis B virus-related cirrhosis. Vaccination consisted of two cycles of three intramuscular double doses (40 μg), given at month 0, 1, 2, and 3, 4, 5, respectively. The first dose was given 2 weeks after stopping lamivudine and the intravenous administration of anti-HBs immunoglobulins. The latter was continued throughout the study and follow-up period to maintain an anti-HBs titre >100 IU/L. Results At the end of both the first and the second vaccination cycle none of the patients developed an anti-HBs titre greater than the basal anti-HBs titre. Conclusion These data confirm and expand our previous data on the lack of effectiveness of conventional recombinant hepatitis B virus vaccination in liver transplant recipients.

Hepatitis A/B vaccination of adults over 40 years old: Comparison of three vaccine regimens and effect of influencing factors

Challenged by contrasting data on low immune responses in the elderly with a combined hepatitis A/B vaccine, a randomised, controlled study was conducted to assess the immunogenicity of three hepatitis A and B vaccination regimens (group 1: combined hepatitis A/B vaccine Twinrix™ [GSK]; group 2: co-administered hepatitis A vaccine, Havrix™ [GSK] + hepatitis B vaccine Engerix™-B [GSK], group 3: co-administered hepatitis A vaccine, Vaqta™ [Sanofi-Pasteur MSD] + hepatitis B vaccine HB VAX PRO™ [Sanofi-Pasteur MSD]) and the effect of influencing factors in subjects >40 years. On completion of the full vaccination course, anti-HBs seroprotection (SP) rates were 92, 80 and 71% in groups 1, 2 and 3, respectively; anti-HAV seropositivity (S+) rates were 97, 99 and 99%, respectively. In group 1, anti-HBs SP rate was non-inferior as well as superior and anti-HAV S+ rate was non-inferior to that in groups 2 and 3. Anti-HBs response was most significantly influenced by the vaccine regimen, followed by age, gender and BMI (stepwise multiple regression analysis). BMI had the most significant influence on HAV response followed by age, gender and vaccine regimen. In conclusion, Twinrix™ induced superior hepatitis B SP rates and similar hepatitis A S+ rates compared to concomitant administration of monovalent vaccines in subjects aged >40 years.

Partial Delipidation Improves the T-Cell Antigenicity of Hepatitis B Virus Surface Antigen

Hepatitis B virus surface antigen (HBsAg) is a complex macromolecular particle composed of glycoproteins and lipids. The latter, representing 25% of the particle mass, are of host origin and determine the solubility, stability, and, indirectly, B-cell immunogenicity of HBsAg. HBsAg is a T-cell-dependent immunogen that does not elicit a detectable humoral immune response in 5% of HBsAg vaccine recipients and in most subjects suffering from chronic hepatitis B. We investigated the influence of the lipid content on the antigenicity of the particle. Lipids were partially removed from HBsAg by treatment with beta-D-octyl glucoside and density centrifugation. Sham treatment consisted of density centrifugation of HBsAg only. We compared the in vitro proliferative responses of established T-cell lines and nonfractionated peripheral blood mononuclear cells (PBMC) from HBsAg vaccinees and chronic HBV patients when stimulated with partially delipidated HBsAg, untreated HBsAg, or sham-treated HBsAg. In all experiments, delipidated HBsAg turned out to be 10 to 100 times more antigenic than its untreated or sham-treated counterpart. Remarkably, PBMC from vaccine nonresponders or chronic HBV patients displayed a proliferative response towards delipidated HBsAg, whereas native HBsAg never induced a response. A series of control experiments demonstrated that this enhancement of T-cell antigenicity was HBsAg specific and directly linked to lipid extraction. Nonspecific adjuvant effects of any kind could be ruled out. In vivo evaluation in mice demonstrated that delipidated particles lose most of their B-cell antigenicity. However, when native and delipidated particles were mixed, these mixtures induced equal or slightly superior anti-HBs responses to those induced by the same quantity of native HBsAg alone. In conclusion, our data show that partial delipidation of HBsAg strikingly increases the T-cell antigenicity of this unique viral antigen.

Antibody Response to Hepatitis B Vaccine in End-Stage Renal Disease Patients

Background: This retrospective and comparative study evaluated the relationship between different factors which may contribute to suboptimal immunological response to intramuscular recombinant hepatitis B vaccine in end-stage renal disease (ESRD) subjects. Methods: From a cohort of 64 dialysis subjects undergoing primary vaccination with Engerix-B^®, we determined the predictive factors that impinged on patients’ response to vaccine, as defined by anti-HBs level ≧10 mIU/l. Dose efficacy was further evaluated by comparing three historical cohorts vaccinated by the regimens of 20, 40 and 80 µg/dose, respectively. Results: We identified 64 ESRD patients (mean age 43 ± 12 years, 81% receiving peritoneal dialysis) who received primary vaccination from April 1997 to September 2004. Median follow-up was 6.5 years. They achieved 81% seroconversion rate. Older age, diabetes mellitus, obesity and low Engerix-B dose were risk factors of inadequate anti-HBs response by univariate analysis. By stepwise logistic regression analysis, hepatitis B vaccine dose was the only independent predictive factor of impaired antibody response. An Engerix-B vaccine dose of 20 µg was associated with more than tenfold increase in risk of non-response to hepatitis B vaccine (hazards ratio 32.2 (95% CI 3.85–250.0)). Immunization with 80 µg of Engerix-B increased the likelihood of persistent protective antibody (log-rank test, p = 0.014). Immunization with Engerix-B 80-µg dose is estimated to prevent one extra ESRD subject who would lose seroprotective anti-HBs level at 1 year for every 5.6 patients treated (number needed to treat to benefit, 5.6 (95% CI 5.4–5.8)). Conclusions: Our results suggest the potential for the three-dose schedule of recombinant vaccine Engerix-B 80 µg to prolong the immune response among ESRD population.

De Novo HBV Infection Caused by an Anti-HBc Positive Donor in a Vaccinated Liver Transplant Recipient In Spite of Anti-HBs Response

De Novo HBV Infection Caused by an Anti-HBc Positive Donor in a Vaccinated Liver Transplant Recipient In Spite of Anti-HBs Response