Seasonal Maintenance of Influenza Vaccine-Induced Antibody Response in Kidney Transplant Recipients

Background/Aims: Although annual influenza vaccination is recommended for kidney transplant recipients, efficacy as reflected by serum antibody titers has not been well studied beyond 1 month in kidney transplant recipients. Methods: We performed a single-center prospective cohort study of 51 kidney transplant recipients and 102 healthy controls receiving the 2006-2007 influenza vaccine. Anti-hemagglutinin antibody titers to A/H1N1, A/H3N2, and B were measured before and 1 month after vaccination, and again at the end of influenza season. The primary outcome was the proportion of participants maintaining seroprotection (antibody titer ≥1:32) for the duration of the influenza season after influenza vaccination. Results: Median follow-up time was 175 and 155 days in the transplant and control groups, respectively. For types A/H1N1 and B, a similar high proportion of the transplant and control groups (88.5 and 81.6% vs. 83.7 and 74.2% for A/H1N1 and B, respectively) maintained seroprotection. For type A/H3N2, significantly less of the transplant group (66.7%) versus the control group (90%) maintained a protective influenza vaccine response (odds ratio 0.21, 95% confidence interval 0.07-0.64). This difference disappeared in adjusted analyses. Actual geometric mean titers decreased significantly within both groups (p < 0.001) but this did not differ between groups. Conclusions: Once they have developed protective vaccine-induced antibody responses to influenza vaccine, kidney transplant recipients are able to maintain adequate protective levels of antibody compared with healthy controls.     

Adequate seroresponse to influenza vaccination in dialysis patients

BACKGROUND: Hemodialysis (HD) patients are immunocompromised, and they have been shown to react suboptimally to recommended vaccinations. Advances in dialysis therapy and other supportive measures may theoretically result in better immune system functions. Clinical evidence supporting this theory has, however, not been presented. With influenza vaccination response, we tried to address this question. METHODS: 42 HD and 15 continuous ambulatory peritoneal dialysis (CAPD) patients were vaccinated with a trivalent influenza vaccine, and the seroresponses at 5 weeks were measured. The results were compared with those of similarly vaccinated 20 nephrology outpatient clinic patients with varying degrees of renal insufficiency and those of 31 cardiac patients with normal renal function. RESULTS: The dialysis patients had higher prevaccination titers of hemagglutination-inhibiting (HI) antibodies to all three vaccine virus antigens than the other groups due to more frequent previous vaccinations. The dialysis patients exhibited lower antibody increases, but an almost comparable proportion of them reached a protective antibody level (HI titers > or =40) 5 weeks after vaccination [A/H3N2: 61% (cardiac patients), 35% (nephrology outpatient clinic patients), 67% (CAPD), and 36% (HD); A/H1N1: 71, 70, 80 and 60; B: 97, 90, 80, and 76%, respectively]. Among the HD group, all patients receiving parenteral calcitriol except 1 (83%), but only 50% of the other HD patients produced protective antibody titers at least to two out of three vaccine virus antigens. No other patient- or HD treatment-associated parameter was significantly related to the vaccination-induced antibody response. CONCLUSIONS: We conclude that influenza vaccination of dialysis patients according to current recommendations may be effective. Additionally, our results suggest that parenteral calcitriol treatment may augment the immune response of HD patients even in a clinically relevant way, an effect so far shown only in in vitro studies.     

The comparison of antibody response to influenza vaccination in continuous ambulatory peritoneal dialysis,hemodialysis and renal transplantation patients

BACKGROUND: The immune system in renal transplant (Tx), Continuous Ambulatory Peritoneal Dialysis (CAPD) and hemodialysis (HD) patients have been suppressed and antibody response to vaccination is weaker than that of the normal population. Additionally immune response to vaccination also differs from each other in aforementioned three groups resulting from different levels immunosuppression. In the present study, detection of antibody response to influenza vaccine as an indicator of the level of immunity in Tx, CAPD and HD patients was aimed PATIENTS AND METHODS: Forty-eight patients (17 Tx, 16 CAPD and 15 HD) and 10 healthy adults, as a control group were enrolled into the study. Purified, split-virus, commercial trivalent influenza vaccine (VAXIGRIP--Pasteur Merieux Connaught, single dose of 0.5 ml into the deltoid muscle) containing 15 microg of each hemagglutinin of A/Johannesburg/82/96 (H1N1), A/Nachang/933/95 (H3N2) and B/Harbin/07/94 (B) strains were administered to all subjects. Serum samples were collected before and 1 month after vaccination to determine antibody titers. Hemagglutination-inhibition test (HI) was applied for determination of antibody response. The antibody response against each strain was measured separately. In addition to measurement of antibody response, increments in antibody titer (n-fold increase in titer), proportion of patients with protective antibody levels and seroconversion levels were taken into account. Wilcoxon paired 2 test and Mann-Whitney U test were applied for statistical analysis. p < 0.05 was accepted as significance level. RESULTS: Significant increases in antibody titers for all three antigens were observed in the study groups after vaccination (p = 0.001). However, the increase in titer of H3N2 was lower in Tx, CAPD and HD patients than that of the control group (1.0-2.0 vs 5.00) (p = 0.01). The proportion of protective antibody titers and seroconvertions were increased after vaccination in all subjects. Proportions of patients with protective antibody titers after vaccination were lower in Tx, CAPD and HD groups in comparison to control group. CONCLUSION: Although antibody titers in Tx, CAPD and HD patients presented significant increases after vaccination, the proportions of patients with protective antibody titers were lower in comparison to control group. Tx, CAPD and HD patients should be vaccinated every year to be able avoid potential morbidity and mortality of the influenza infection. Trial of high dose vaccination protocols may be useful to increase the proportion of patients with protective antibody levels.     

Influenza vaccination in heart transplant recipients.

Seventy-nine heart transplant recipients were vaccinated with a trivalent influenza virus vaccine 1996/97 containing the strains A/Singapore/6/86 (H1N1), A/Wuhan/395/95 (H3N2), and B/Beijing/184/93. The proportions of patients with protective levels of antibody (HI > or = 40) after vaccination ranged from 100% (A/Singapore [H1N1]) to 31.6% (B/Beijing) and their mean fold titer increases were lower than those recorded for vaccination of 109 healthy subjects with the same batch of vaccine. The vaccinations were tolerated well and did not result in serious side effects, such as graft rejections. Our findings indicate that influenza vaccination can induce protective antibody levels in a substantial proportion of heart transplant recipients and lend support to the recommendation to vaccinate such patients annually against influenza.     

Natural influenza infection produces a greater diversity of humoral responses than vaccination in immunosuppressed transplant recipients

The humoral immune response to influenza virus infection is complex and may be different compared to the antibody response elicited by vaccination. We analyzed the breadth of IgG and IgA responses in solid organ transplant (SOT) recipients to a diverse collection of 86 influenza antigens elicited by natural influenza A virus (IAV) infection or by vaccination. Antibody levels were quantified using a custom antigen microarray. A total of 120 patients were included: 80 IAV infected (40 A/H1N1 and 40 A/H3N2) and 40 vaccinated. Based on hierarchical clustering analysis, infection with either H1N1 or H3N2 virus showed a more diverse antibody response compared to vaccination. Similarly, H1N1-infected individuals showed a significant IgG response to 27.9% of array antigens and H3N2-infected patients to 43.0% of antigens, whereas vaccination elicited a less broad immune response (7.0% of antigens). Immune responses were not exclusively targeting influenza hemagglutinin (HA) proteins but were also directed against conserved influenza antigens. Serum IgA responses followed a similar profile. This study provides novel data on the breadth of antibody responses to influenza. We also found that the diversity of response is greater in influenza-infected rather than vaccinated patients, providing a potential mechanistic rationale for suboptimal vaccine efficacy in this population.     

Influenza vaccination in chronic hemodialysis patients. The effect of zinc supplementation.

Since influenza increases the mortality of chronically ill patients we decided to study the effectiveness of influenza vaccination in hemodialysis (HD) patients. Nineteen HD patients aged from 20 to 60 years, on unrestricted diet and with no febrile episode, were studied. Blood samples were collected before the intramuscular injection of 0.5 mL multivalent influenza vaccine (Inflexal Berna) and every 2 weeks thereafter. At the end of 4th week a second vaccination was done and a dosage of 200 mg of zinc acetate (60 mg elemental zinc) was given daily to each patient for at least 4 weeks. Before vaccination the antibody titers to influenza virus ranged from 1:10 to 1:80 and after vaccination from 1:20 to 1:640. Four weeks after vaccination 6/19 (31.5%), 8/19 (42%), and 10/19 (52.5%) patients showed a fourfold or greater increase at serum antibody titers to antigens A/Singapore, A/Sichuan, and B/Beijing, respectively. The zinc supplementation after the second vaccination induced a similar increase of serum antibody titers to the A/Singapore but some even greater increase of the antibody titers to the A/Sichuan and B/Beijing. Serum immunoglobulins and complement components C3/C4 were not changed during this study. It is suggested that about 50% of uremic patients respond to the influenza vaccination and that zinc treatment does not increase this responsiveness.     

Influenza virus vaccination in kidney transplant recipients: serum antibody response to different immunosuppressive drugs

Salles MJC, Sens YAS, Boas LSV, Machado CM. Influenza virus vaccination in kidney transplant recipients: serum antibody response to different immunosuppressive drugs.
Clin Transplant 2010: 24: E17–E23. © 2009 John Wiley & Sons A/S.   Abstract: 
Introduction:  This study prospectively accessed the immune response to the inactivated influenza vaccine in renal transplant recipients receiving either azathioprine or mycophenolate mofetil (MMF). Side effects were investigated.
Methods:  Sixty-nine patients received one dose of inactivated trivalent influenza vaccine. Antihemagglutinin (HI) antibody response against each strain was measured before and one to six months after vaccination.
Results:  Geometric mean HI antibody titers for H1N1 and H3N2 strains increased from 2.57 and 2.44 to 13.45 (p = 0.001) and 7.20 (p < 0.001), respectively. Pre- and post-vaccination protection rates for H1N1 and H3N2 increased from 8.7% to 49.3% (p < 0.001); and 36.3% (p < 0.001) and seroconversion rates were 36% and 25.3%, respectively. There was no response to influenza B. The use of MMF reduced the H1N1 and H3N2 protection rates and the seroconversion rate for the H1N1 strain when compared with the use of azathioprine, and subjects transplanted less than 87 months also had inferior antibody response. Adverse events were mild and there were no change on renal function post-vaccination.
Conclusion:  Renal transplant patients vaccinated against influenza responded with antibody production for influenza A virus strains, but not for influenza B. Use of MMF and shorter time from transplantation decreased the immune response to the vaccine.     

Influenza Vaccination in Chronic Hemodialysis Patients. The Effect of Zinc Supplementation

Since influenza increases the mortality of chronically ill patients we decided to study the effectiveness of influenza vaccination in hemodialysis (HD) patients. Nineteen HD patients aged from 20 to 60 years, on unrestricted diet and with no febrile episode, were studied. Blood samples were collected before the intramuscular injection of 0.5 mL multivalent influenza vaccine (Inflexal Berna) and every 2 weeks thereafter. At the end of 4th week a second vaccination was done and a dosage of 200 mg of zinc acetate (60 mg elemental zinc) was given daily to each patient for at least 4 weeks. Before vaccination the antibody titers to influenza virus ranged from 1:10 to 1:80 and after vaccination from 1:20 to 1:640. Four weeks after vaccination 6/19 (31.5%), 8/19 (42%), and 10/19 (52.5%) patients showed a fourfold or greater increase at serum antibody titers to antigens A/Singapore, A/Sichuan, and B/Beijing, respectively. The zinc supplementation after the second vaccination induced a similar increase of serum antibody titers to the A/Singapore but some even greater increase of the antibody titers to the A/Sichuan and B/Beijing. Serum immunoglobulins and complement components C₃/C₄ were not changed during this study. It is suggested that about 50% of uremic patients respond to the influenza vaccination and that zinc treatment does not increase this responsiveness.     

Safety and efficacy of influenza vaccination in renal transplant recipients

This Practice Point commentary discusses Scharpé et al.'s single-center, nonrandomized, prospective trial of influenza vaccination in renal transplant recipients. In total, 165 transplant recipients and 41 healthy volunteers were vaccinated with a standard inactivated trivalent influenza vaccine (containing strains of the A/H1N1, A/H3N2 and B viruses). No rejection episodes or other adverse events were reported in either group. Influenza-specific antibody titers increased in renal transplant recipients following vaccination, as measured by comparison of pre-vaccination and post-vaccination seroprotection and seroresponse rates. This commentary discusses the limitations of the trial, and urges caution in extending the conclusions drawn by Scharpé et al. regarding the safety of the trivalent, non-adjuvant-containing influenza vaccine to newer adjuvant-assisted vaccines. Annual vaccination for influenza by use of the trivalent vaccine strategy without adjuvant should, however, be standard of care for all stable renal transplant recipients who do not have clinical contraindications.     

Granulocyte-macrophage colony-stimulating factor as an adjuvant to hepatitis B vaccination in maintenance hemodialysis patients

Patients on maintenance hemodialysis (HD) have poor seroconversion rate after hepatitis B vaccination. The present study was designed to test the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjuvant to hepatitis B vaccination for improving seroconversion rate in maintenance HD patients. Twelve chronic HD patients were randomly assigned to receive either hepatitis B vaccination alone or hepatitis B vaccination 24 h after 1 dose of GM-CSF for primary immunization. A group of 16 chronic HD patients who had not seroconverted after a standard two-dose hepatitis B vaccination were randomly assigned either to a booster dose of hepatitis B vaccine alone or a booster dose given 24 h after one dose of GM-CSF. In the primary immunization group only 2 of 6 patients (33%) who had received vaccination alone, versus 5 of 6 patients (83%) who had received hepatitis B vaccine after one dose of GM-CSF, developed seroprotective antibody titers. Moreover, seroprotective antibody titers (IU/ml) were significantly higher in the latter group (275 +/- 286.5 vs. 14 +/- 22, p < 0.05). In patients who had not seroconverted with prior hepatitis B vaccination, GM-CSF adjuvant therapy significantly increased the seroconversion rate versus booster dose alone (87.5 vs. 25%, respectively, p < 0.02), with significantly higher seroprotective antibody titers (84 +/- 80 vs. 19 +/- 33 IU/ml, respectively, p < 0. 05). These findings suggest that administration of one dose of GM-CSF, as adjuvant therapy, prior to primary or booster dose hepatitis B vaccination may significantly increase seroconversion rate and seroprotective antibody titers in chronic HD patients.     

Hepatitis B vaccination in human immunodeficiency virus-infected adults receiving hemodialysis

BACKGROUND: The Centers for Disease Control and Prevention (CDC) recommends hepatitis B virus (HBV) immunization for all hemodialysis (HD) patients because they are at high risk of infection. Several studies have shown that the development of protective antibody titers after HBV vaccination is much lower in HD patients. We hypothesized that human immunodeficiency virus (HIV) infection in patients with end-stage renal disease (ESRD) would further impair the immune response to hepatitis B vaccination. METHODS: We performed a retrospective cohort study of patients undergoing long-term hemodialysis from 1990 to 2002 at the United States-based dialysis facilities of Gambro Corporation, North America. The response rate defined as an increase in anti-HBs levels >/=10 mIU/L after a month of the third dose of HBV vaccination was determined in HIV-infected and a randomly selected group of ESRD patients. The demographic information, laboratory data, and hepatitis B surface antibody (anti-HBs) titers were recorded from the Gambro Corporation database on these patients. RESULTS: Of the 347 adult HIV ESRD patients, 116 received three doses of recombinant hepatitis B vaccination. Seventy percent were male, and the majority (86%) were black. Of the 116 patients who received three doses of HBV vaccination, 62 (53.4%) developed protective antibody titers. This was comparable to the response rate of 50.4% in the randomly selected 220 non-HIV hemodialysis patients. Among HIV ESRD patients, the mean hemoglobin (Hgb) was higher in patients who developed protective antibody titers (Hgb 11.61 +/- 2 vs. 10.55 +/- 1.86, P value <0.01). On multivariate logistic regression analysis, higher Hgb was associated with protective antibody titers (odds ratio: 1.34, 95% CI 0.99-1.72). Seventy percent of the HIV-infected responders maintained protective antibody titers 6 months after vaccination. CONCLUSION: Hepatitis B vaccination should be offered to all HIV-infected ESRD patients because over half of the patients with HIV and ESRD can develop protective antibodies.     

Good response to HBsAg vaccine in dialysis patients is associated with high CD4+/CD8+ ratio

Objective

Chronic renal failure is accompanied by various abnormalities of innate and acquired, cellular and humoral immunity. We aimed to investigate whether positive Candida skin test results, CD4+ and CD8+, before the first dose of vaccination could be a predictor for antibody response to hepatitis B vaccination and the relation of these parameters with hepatitis B antibody levels 1?month after the last dose of vaccination.

Materials and methods

The present study was carried out in 57 dialysis patients. All patients received recombinant hepatitis B vaccine (40???g) given intramuscularly in the deltoid muscle in a four-dose schedule at 0, 1, 2, and 6?months. Candida skin test and lymphocyte subsets (CD4+ and CD8+) were determined before the first dose of vaccination and 1?month after the fourth inoculation of hepatitis B vaccine.

Results

Ten patients (17.5%) were non-responders (HBsAb??100?IU/L), which was determined 1?month after the fourth dose of vaccination. Thirty-nine patients (68.4%) and 44 patients (77.2%) were anergic to Candida skin test before the first dose and 1?month after fourth inoculation of hepatitis B vaccine, respectively. There was no relationship between Candida skin test and response to hepatitis B vaccination. Mean age was lower, and CD4+/CD8+ ratio measured both before and after vaccination was higher in good responders compared with that of weak responders and that of non-responders. Females were better responders than males.

Conclusion

High skin test anergy rate and low seroconversion rate after hepatitis B vaccination are important problems in patients on dialysis. Females, younger patients, and patients with higher CD4+/CD8+ ratio have better HBsAb antibody response to hepatitis B vaccination.     

Impact of adjuvanted H1N1 vaccine on cell-mediated rejection in heart transplant recipients

During the H1N1 influenza virus pandemic, vaccination of high risk groups including solid-organ transplant recipients was advised. A retrospective case control study of 60 heart transplant patients, 15 having received the H1N1 virus antigen and ASO3 adjuvant vaccine (GlaxoSmithKline, Mississauga, ON, Canada) within 21 days and 45 having not been vaccinated, all undergoing routine surveillance endmyocardial biopsies, was performed. The overall rate of cellular rejection (all grades) was not statistically different between groups; however, acute cellular rejection, ≥grade 2 (1990 ISHLT criteria), was more frequent among those having recently vaccinated (control: 1/45 vs. 6/15, p = 0.001). On multivariate analysis, the only risk factor found to be associated with acute cellular rejection was recent H1N1 viral antigen and adjuvant vaccination (OR 26.5: 95% CI 02.59-270.5). Vaccine adjuvants increase host response to vaccine antigens by immune upregulation potentially increasing risk of rejection in solid-organ transplant recipients. The potential hazard of vaccination this study raises must be weighed with the clear benefit vaccination has proven to be.     

Influenza virus immunization effectivity in kidney transplant patients subjected to two different triple-drug therapy immunosuppression protocols: mycophenolate versus azathioprine

BACKGROUND: Due to possible complications and treatment limitations, the prevention of influenza in renal transplant (RT) patients is highly indicated. METHODS: Forty-nine patients with a 1-year functioning RT subjected to two different immunosuppressive regimens and 37 healthy relatives (HR) were administered the anti-influenza vaccine as recommended for 1996 to 1997. Anti-influenza antibody, creatinine, and immunological markers were estimated at 1 and 3 months after vaccination. RESULTS: Three months after vaccination, 46.2% of the RT patients and 69% of the HR (P=0.06) showed protective antibody titers to influenza A (relative risk [RR]; 0.67; 95% confidence interval: 0.44-1.02). A total of 20.5% of the RT patients and 44.8% of the HR showed antibodies to influenza B (P=0.03). Despite these differences, the incidence of illness was similar. The immunosuppressive regimen had no effect on the antibody response. CONCLUSIONS: Although the RT patients showed a reduced antibody response, no negative effects on graft outcome were observed.     

Comparison of the Immunogenicity of a Monovalent Influenza A/H1N1 2009 Vaccine Between Healthy Individuals,Patients With Chronic Renal Failure,and Immunocompromised Populations

Background

Data on the immunogenicity (IG) of the influenza vaccine among patients at high risk of influenza-related complication are limited.

Methods

We studied the antibody titer following a single dose of monovalent 2009 influenza A (H1N1) vaccine between groups of adult patients who were healthy, those with chronic renal failure (CRF), kidney transplant (KT) recipients, and human immunodeficiency virus (HIV)-infected patients. The IG (primary endpoints) was accessed at 4 weeks after vaccination. The secondary endpoint was safety of the vaccine.

Results

A total of 293 patients were studied. Patients' mean age was 41(standard deviation [SD], 13.3) years old. At baseline, mean age (P < .001), history of vaccination in a prior year (P < .001), and geometric mean titers (GMT; P < .001) significantly differed between each groups and the majority (70%) of participants had the hemagglutination inhibition titer <1:10. The IG of the vaccine was highest in the healthy group (71.4 %). The response rate among CRF, KT, and HIV groups was 42.4% (risk ratios [RR], 0.72; 95% confidence interval [CI], 0.5–1.02), 31.9% (RR, 0.51; 95% CI, 0.34–0.76), and 29.7% (RR, 0.42; 95% CI, 0.3–0.6), respectively. The vaccine was well-tolerated in all studied groups. Thirty (10.2%) patients experienced at least 1 adverse reaction but systemic reaction was uncommon (3.4%).

Conclusions

A single dose of monovalent 2009 influenza A (H1N1) vaccine result in poor IG among high-risk populations, including CRF, KT and HIV patients.     

Influenza Vaccination in Orthotopic Liver Transplant Recipients: Absence of Post Administration ALT Elevation

Influenza vaccination has reduced life-threatening complications from influenza virus infection in adult liver transplant recipients. We evaluated changes in aminotransferase level and immunogenicity of influenza vaccination in liver transplant recipients. Fifty-one liver transplant recipients were administered a standard dose of the 2002-2003 inactivated trivalent influenza vaccine. ALT values were measured at baseline, 1 week and 4-6 weeks postvaccination. Antibody responses to each component of the vaccine were measured at baseline and after 4-6 weeks by a hemagglutination inhibition (HAI) assay. Response was defined as an HAI titer > or = 1: 40 and/or a 4-fold increase in antibody titers from baseline. An ALT elevation was defined as a rise of > or = 50% from baseline. There was no difference in the median rise in ALT value between seroconverters and nonseroconverters. A significant number of recipients developed potentially protective antibody titers (p-value < 0.0001). At less than 4 months post transplantation, 1/7 (14%), at 4-12 months, 6/9 (67%), and after 12 months, 30/35 (86%) subjects responded to the H1 strain. Of 51 recipients, one HCV (-) recipients vaccinated within 3 months of transplantation developed acute cellular rejection. Influenza virus vaccination is not associated with allograft rejection or ALT flares in liver transplant recipients.     

T cell subsets required for in vivo and in vitro responses to single and multiple minor histocompatibility antigens.

The requirement for helper T cells in the in vivo and in vitro T cell response to a diverse panel of minor histocompatibility antigens in mice was investigated. Target H antigens included: (a) multiple antigens distinguishing H-2-matched, inbred strains, and (b) single H antigens, including H-4, H-3, and the male-specific (H-Y) antigen. The involvement of helper T cells in skin allograft rejection and CTL priming was evaluated by pretreating graft recipients with anti-CD4 antibody. Anti-CD4 treatment had no effect on rejection of H-3- and H-4-incompatible skin grafts, but slowed rejection of male and BALB.B skin grafts. Comparable pretreatment with anti-CD4 antibody in vivo eliminated the priming of H-4-specific CTL, multiple B10.BR anti-CBA/J CTL, and all but a minor C57BL/6 anti-BALB.B CTL population. However, CTL specific for the two classes of H antigens, single and multiple minor H antigens, differed in their in vitro requirements for CD4+ helper T cells: (a) multiple antigen-specific CTL required CD4+ helper T cells for optimal expansion, and (b) CTL specific for single H antigens expanded in the absence of helper T cells. The CTL specific for all tested H antigens were CD8+ T cells. These results suggest that CD4+ helper T cells are not always required for effective skin allograft rejection or CTL expansion in vitro; the requirement for helper T cells is apparently dependent upon the identity of the stimulatory minor H antigen(s). This variable dependency contrasts with the evident requirement for helper T cells in the in vivo priming of CTL specific for minor H antigens.     

Comparison of Intramuscular and Intradermal Applications of Hepatitis B Vaccine in Hemodialysis Patients

This study compared the application of intramuscular recombinant hepatitis B vaccine in hemodialysis patients with the application of accelerated intradermal recombinant hepatitis B vaccine, which can be applied with one-tenth of the standard dose. Sixty seronegative patients for hepatitis B were randomly separated into two groups. Twenty μg of the recombinant hepatitis B vaccine was intramuscularly applied at 0-, 1-, 2-, and 6-month intervals to the first group (32 cases). One more dose was applied at month 12 to those whose anti-HBs titers remained below 100 mIU/mL at month 7. The same vaccine was intradermally applied at 2μg dose six times with one-month intervals to the second group (28 cases). Vaccine applications were continued in those whose anti-HBs titers remained below 100 mIU/mL at month 7 until antibody titers reached above this value or until the dose number became 12. Measurements of antibody titers were repeated at month 13 in both groups. As a result, in the vaccination of hemodialysis patients against hepatitis B, the accelerated ID application of hepatitis B vaccine with a dose reduced to one-tenth is more cost-effective than the standard dose vaccination schedules. Especially for hemodialysis patients, the time has come for routine application of ID hepatitis B vaccine as an alternative vaccination method.     

Comparison of intramuscular and intradermal applications of hepatitis B vaccine in hemodialysis patients

This study compared the application of intramuscular recombinant hepatitis B vaccine in hemodialysis patients with the application of accelerated intradermal recombinant hepatitis B vaccine, which can be applied with one-tenth of the standard dose. Sixty seronegative patients for hepatitis B were randomly separated into two groups. Twenty mug of the recombinant hepatitis B vaccine was intramuscularly applied at 0-, 1-, 2-, and 6-month intervals to the first group (32 cases). One more dose was applied at month 12 to those whose anti-HBs titers remained below 100 mIU/mL at month 7. The same vaccine was intradermally applied at 2 microg dose six times with one-month intervals to the second group (28 cases). Vaccine applications were continued in those whose anti-HBs titers remained below 100 mIU/mL at month 7 until antibody titers reached above this value or until the dose number became 12. Measurements of antibody titers were repeated at month 13 in both groups. As a result, in the vaccination of hemodialysis patients against hepatitis B, the accelerated ID application of hepatitis B vaccine with a dose reduced to one-tenth is more cost-effective than the standard dose vaccination schedules. Especially for hemodialysis patients, the time has come for routine application of ID hepatitis B vaccine as an alternative vaccination method.     

Response to an experimental HBV vaccine permits withdrawal of HBIg prophylaxis in fulminant and selected chronic HBV-infected liver graft recipients.

Strategies using lamivudine and hepatitis B immunoglobulins (HBIg) for prevention of hepatitis B virus (HBV) reinfection after liver transplantation (LT) are expensive since life-long treatment is needed. We evaluated the possibility to obtain protective hepatitis B surface antigen (HBsAg) antibody (anti-HBs) titers after LT and to discontinue HBIg prophylaxis after a reinforced course of vaccination against HBV using an experimental adjuvant HBsAg / AS04 vaccine (GlaxoSmithKline Biologicals [GSK], Rixensart, Belgium) in patients transplanted for hepatitis B. Fifteen LT patients on stable low-level immunosuppression were vaccinated with a double dose of the vaccine at 0, 1, 2, 6, and 12 months: 5 patients were transplanted for nonviral diseases and 10 patients were transplanted for HBV on HBIg monotherapy. HBIg were continued during baseline vaccination (0, 1, and 2 months) and when anti-HBs titers determined every 6 weeks dropped below 150 IU/L. Overall follow-up was 18 months. Sustained long-term response to vaccination was defined as anti-HBs titers >500 IU/L without further need for HBIg administration during a follow-up period of at least 12 months. Overall sustained response to vaccination was 53% (8 / 15 patients); 80% (4 / 5 patients) in the nonviral disease group and 40% (4 / 10 patients) in the HBV group (2 /2 fulminant and 2/8 chronically infected patients) developed a sustained long-term response and were completely free of HBIg at the end of the 18-month follow-up. No HBV recurrence, rejection episodes, or side effects occurred during the follow-up. In conclusion, protective anti-HBs titers were obtained in a substantial number of LT patients following a reinforced course of HBV vaccination with vaccines containing new immunostimulating adjuvants. Vaccination seems well tolerated and safe and allows long-term discontinuation of HBIg.