Low dose intradermal vaccination is superior to high dose intramuscular vaccination for hepatitis B in unresponsive hemodialysis patients

After two intramuscular (IM) vaccination protocols (40 microg at 0, 1, 2, and 6 months), patients who were unresponsive to hepatitis B vaccination were collected from three HD centers. The aim of this study was to compare the effectiveness of intradermal (ID) and repeated IM vaccination protocols. Thirty-three of 639 HD patients were found to be unresponsive. Patients were randomly assigned into two groups: one to receive 80 microg ID and the other 160 microg IM vaccination protocol. Both ID (p = 0.000) and IM (p = 0.03) groups disclosed statistically significant seroconversion rates six months after the last vaccination dose. The seroconversion rate was 94.1% in the ID and 50% in the IM groups - showing a significant improvement in the ID group (p = 0.011). A low-dose ID is superior to standard IM vaccination protocol and also more cost-effective in unresponsive HD patients.     

Levamisole treatment enhances protective antibody response to hepatitis B vaccination in hemodialysis patients

Hemodialysis shows a high risk for hepatitis B infection, and hepatitis B virus (HBV) vaccination has now become a routine procedure. Unfortunately, 40% to 50% of hemodialysis patients do not have adequate protective antibodies against the HBV vaccination which is thought to be due to depressed cell mediated immunity. Levamisole has been reported to stimulate depressed T-cell activity and enhance B lymphocyte function and restore delayed hypersensitivity reactions in immune-depressed patients. We studied the effects of levamisole, an immunomodulatory agent, on the protective antibody response of hemodialysis patients to the HBV vaccination. Our hemodialysis patients with negative anti-HBs antibody routinely received 40 microg doses of recombinant HBV vaccine intramuscularly at 0, 1, and 6 months, and we followed serum anti-HBs levels. Patients with a serum antibody level of >10 mIU/ml were considered as responders. Study groups were classified as follows. Group 1 was comprised of 96 chronic hemodialysis patients with negative anti-HBs and HBV core antibody (52 male, 44 female, mean age of 45 +/- 15 years and mean hemodialysis duration of 46 +/- 40 months) who received HBV vaccination; 55 patients (57%) were found to be responders. Group 2 was comprised of 19 randomly selected patients who had never received hepatitis B vaccine (13 male, 6 female, mean age of 42 +/- 14 years, mean duration of hemodialysis 31 +/- 27 months) and who were started on an HBV vaccination protocol with levamisole per os 80 mg after each hemodialysis session for 4 months and followed up on serum anti-HBs levels. Seventeen of the patients completed this levamisole treatment. Fourteen of the 17 patients had the levels of the protective serum antibody indicating a higher response rate when compared with patients who did not receive levamisole (82% versus 57%, respectively, p < 0.05). Group 3 was comprised of 19 patients randomly selected from persons who did not respond to previous vaccination programs (10 male, 9 female, mean age of 51 +/- 14 years, mean duration of hemodialysis 41 +/- 31 months). A second HBV vaccination program was started with the same levamisole protocol. In this group, 18 patients completed this treatment model. Fourteen of them responded to the vaccination model. In Group 4, a second HBV vaccination program was applied without levamisole to 20 randomly selected persons who did not respond to the previous routine vaccination program (12 male, 8 female, mean age of 53 +/- 17 years, mean duration of dialysis 51 +/- 38 months). Only 3 of them responded to a second vaccination program. Comparing Group 3 with Group 4, there was a higher responder rate to HBV vaccination (77% versus 15%, respectively, p < 0.0001). These results show that levamisole treatment increases the response rate to the first HBV vaccination and of the previously unresponsive cases by modulating possible cellular immune response.     

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.     

Factors influencing the response to hepatitis B vaccination of hemodialysis patients

The response rate and HBsAG antibody concentrations were examined after hepatitis B vaccination in 78 hemodialysis patients aged between 29 and 79 years. The values were related to age, duration of hemodialysis, body weight, creatinine, urea nitrogen, serum concentrations of beta 2-microglobulin and soluble interleukin-2 receptor (IL-2R). Patients with low anti-HBsAG antibody concentrations (10-100 mU/ml) had significantly higher IL-2R serum concentrations than those with high anti-HBsAG antibody concentrations (greater than 3,000 mU/ml; p less than 0.05). Discriminant multivariate analysis (p = 0.032) revealed the influence (62%) of IL-2R on the response rate while other factors were similar in all patient groups. It is concluded that preactivation of T cells with an increased release of IL-2R may contribute to impaired immune response after hepatitis B vaccination.     

Immunization and vaccination protocol in hemodialysis patients with naturally acquired hepatitis B antibody.

Long-term behavior of naturally acquired anti-HBs antibody was tested every 6 months for 3 years in 22 dialysis patients. Fifteen of them maintained protective levels throughout follow-up (102 and 85.5 mUI/ml at the beginning and the end, respectively). Seven of them became anti-HBs and were submitted to a 40-micrograms booster injection of hepatitis B vaccine. Seroconversion was observed in 6 of 7 patients (85.7%) with a mean anti-HBs titer of 90.4 and 47.3 mUI/ml after 3 and 6 months, respectively. Protective anti-HBs level may be maintained longer in patients with natural immunity than in HBsAg-negative vaccinated subjects. Effectiveness of a reduced vaccination protocol in patients who have lost their natural immunization should be confirmed with further studies.     

Effect of levamisole supplementation on hepatitis B virus vaccination response in hemodialysis patients

Aim:   As an immune-modulating agent, levamisole has been reported to stimulate depressed T-cell activity, enhance B lymphocyte function and restore delayed hypersensitivity reactions in immune-depressed patients. There are a number of recent studies claiming that levamisole can improve response rate to hepatitis B virus (HBV) vaccination in haemodialysis patients. The present study has examined this hypothesis amongst some Iranian patients, using double-blind randomized clinical trial.
Methods:   During a 12 month period, 70 patients on maintenance haemodialysis with negative anti-hepatitis B surface antibody (HBsAb) and HBV core antibody (HBcAb), from four different dialysis centres were enrolled into the study. The patients were randomized to two groups. The first group (levamisole group) received 40 μg doses of recombinant HBV vaccine i.m. at 0, 1 and 6 months, plus 100 mg levamisole p.o., after each haemodialysis session. The second group (placebo group) received the same vaccination protocol, except for the placebo instead of levamisole. The patients were followed on serum HBsAb level. Those with an HBsAb level of above 10 mIU/mL, 1 month after the third dose of vaccination, were considered as responders.
Results:   The levamisole group was comprised of 38 patients and the placebo group of 32 patients. Thirty-one patients (81.6%) of levamisole group and 26 patients (81.3%) of placebo group responded to vaccination. The difference between two groups was not significant.
Conclusion:   This study indicated that in a haemodialysis population with high response to HBV vaccination, levamisole might have no significant effect in enhancing the response. Further studies with higher power can give more accurate results.     

Immune response to hepatitis B vaccine in hemodialysis patients

The impaired immune reactivity of hemodialysis patients has been reported to interfere with adequate antibody responses to standard doses of hepatitis B vaccine. In 22 hemodialysis patients, however, a 92% conversion rate could be obtained by administering multiple doses of plasma-derived MSD-vaccine. As the cost of such an amplified vaccination schedule is still lower than the cost of one dialysis treatment, this active vaccination policy for highly susceptible patients appears financially justified.     

Loss of hepatitis B immunity in hemodialysis patients acquired either naturally or after vaccination

AIM: The aim of our study was the long-term evolution of hepatitis B immunity and the titers of antibodies against the surface antigen (anti-HBs) acquired either naturally or after vaccination in hemodialysis (HD) patients with no history of hepatitis C virus (HCV) infection. METHODS: 36 HD patients were vaccinated with 4 doses of 40 microg recombinant B vaccine (Engerix, Rixensart, Belgium), intramuscularly at 0, 1, 2 and 6 months. 21 patients (60%) seroconverted developing anti-HBs titers > or = 10 IU/ml. Two patients were transferred to another unit before completion of 6 months after the last vaccine dose. We followed-up 19 HD patients who were immune against HBV after vaccination (Group A), and 30 immune patients (anti-HBs titers > or = 10 IU/ml) who had never been vaccinated and had antibodies against the core antigen (anti-HBc), diagnostic of natural HBV infection (Group B). In all patients of Groups A and B, anti-HBs were determined every 6 months, starting 6 months after the last dose in the vaccinated patients. Follow-up period lasted from October 2002 - April 2006. RESULTS: The mean follow-up in Group A was 21 +/- 12 months (range 6 - 36) and in Group B 29 +/- 12 months (range 6 - 42). Age, sex, presence of diabetes mellitus and duration of dialysis did not differ between the two groups. Five patients in Group A (26%) and 2 patients in Group B (9%) lost immunity (anti-HBs < 10 IU/ml) (p = 0.07). The median time to loss of immunity in Group A patients was 12 months (interquartile range 6 - 18 months), while in Group B patients it was 15 months (interquartile range 12 - 18 months). No booster dose was administered during the study. The 2 patients of Group B who lost immunity were the oldest of the group and redeveloped anti-HBs 6 and 12 months after they had lost it. During the first 6 months of the follow-up period, Group A had significantly higher anti-HBs titers than Group B (p < 0.05). However, this difference was lost later on, and after the first year of follow-up, anti-HBs titers were decreased significantly in Group A (p < 0.05), but remained unchanged in Group B throughout the follow-up period. CONCLUSIONS: In conclusion, HD patients lost hepatitis B immunity both after natural infection or vaccination, but naturally infected patients easily redeveloped protective anti-HBs titers. Anti-HBs titers decreased faster in vaccinated patients than in those with natural acquired immunity who held stable titers for a longer period. It is suggested that HD patients should be followed-up regularly for loss of HBV immunity after vaccination and receive a boosting dose when this occurs. In contrast, patients who acquired natural immunity do not need any anamnestic vaccination.     

Intracutaneous versus intramuscular hepatitis B vaccination in primary non-responding haemodialysis patients

OBJECTIVE: To determine whether hepatitis B vaccination given intracutaneously(IC) is more effective than intramuscularly (IM) in primarynon-responding haemodialysis patients. DESIGN: A prospective, randomized study of antibody responses to hepatitisB vaccine given IC or IM, in 25 haemodialysis patients. Outcomemeasures were rates of seroconversion, mean and geometric meanlevels of antibody achieved, and antibody levels 1 year aftervaccination. RESULTS: With a dosing schedule of 10 µg vaccine once a week ICin the skin overlying the deltoideus muscle of the non-dominantarm during 12 consecutive weeks, antibody levels to hepatitisB surface antigen (anti-HBsAg) of 10 IU/l or more were achievedin nine of 10 evaluable patients, with a geometric mean of 70IU/l. Nine months after the end of the vaccination anti-HBsAglevels had dropped to 9±4 IU/l (M±SE), with ageometric mean of 5 IU/l, in the nine remaining evaluable patients. With a dosing schedule of 40 µg vaccine i.m. in the deltoideusmuscle of the non-dominant arm at 0, 1, and 3 months, anti-HBsAglevels of at least 10 IU/l were achieved in eight of 14 evaluablepatients, with a geometric mean of 94 IU/l. Nine months afterthe end of the vaccination anti-HBsAg levels had dropped to16±7 IU/l, with a geometric mean of 9 IU/l, in the nineremaining evaluable patients. Anti-HBsAg levels at 8 and 12weeks were higher in the IC than in the group receiving vaccineIM (at 8 weeks 134±76 vs 39±20 IU/l, P<0.05,and at 12 weeks 188±98 vs 47±18 IU/l P<0.01).The half-time of anti-HBsAg is about 13 weeks, both when theaveraged absolute and when the geometric mean levels are usedfor the estimate. CONCLUSIONS: The intracutaneous route is a less practical but effective methodof vaccination against hepatitis B in primary non-respondinghaemodialysis patients. The weekly 10 µg vaccine IC schemeresulted in the fastest development of protective antibody levels,within 8 weeks, which may be useful in previously non-immunepersons who may be infected with hepatitis B virus (e.g. needle-stickaccidents).     

Influence of thymopentin on antibody response, and monocyte and T cell function in hemodialysis patients who fail to respond to hepatitis B vaccination

We investigated the influence of thymopentin as an adjuvant for hepatitis B vaccination on in vitro monocyte and T cell function and in vivo antibody response in a prospective, placebo-controlled double-blind trial in 20 low- and nonresponders to hepatitis B vaccination on chronic hemodialysis. 50 mg thymopentin was given subcutaneously twice per week for 3 weeks, followed by 1 intramuscular injection of 40 micrograms HB-Vax and 3 subsequent injections of thymopentin. After 1 month, the patients were boostered with 40 micrograms HB-Vax. There was no significant difference in T cell and monocyte function after administration of thymopentin, as determined in vitro. After 3 months, 3 patients in the placebo and 2 patients in the thymopentin group had antibody titers greater than 10 U/l. In both groups only patients with normal or slightly impaired monocyte function responded to vaccination. Thus, we were not able to demonstrate a beneficial effect of thymopentin on hepatitis B vaccination in nonresponders on chronic hemodialysis. Furthermore, functional tests were not able to identify a subpopulation of uremic nonresponders who would benefit from thymopentin.     

Systematic review of the efficacy and safety of intradermal versus intramuscular hepatitis B vaccination in end-stage renal disease population unresponsive to primary vaccination series

Abstract

Introduction: The response to hepatitis B vaccine in the dialysis population is reduced compared to the general population. The intradermal (ID) hepatitis B vaccine has been studied as a potential alternative to intramuscular (IM) administration. This alternative route of administration may illicit a response via a distinct immunologic pathway that may help achieve higher seroconversion rates and thus, protection against hepatitis B infection in this vulnerable patient population. Methods: A literature search was performed in January 2015 using Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials with keywords including, hepatitis B vaccines, intradermal, dermal, intracutaneous, dialysis, hemodialysis, continuous ambulatory peritoneal dialysis, CAPD, peritoneal dialysis, renal failure, chronic renal failure, chronic kidney disease, chronic renal insufficiency, End Stage Renal Disease, ESRD, and CKD. Our search strategy was restricted to human studies published in the English language, and additional literature was retrieved by hand-searching bibliographies of relevant articles. Two reviewers (F.Y. and S.G.) independently reviewed abstracts and/or full texts of articles retrieved from the electronic database using the above-mentioned search strategy. Inclusion criteria were as follows: (1) Published, English-language studies performed in the human population, (2) adult patient population (≥18 years of age), (3) randomized trials, (4) patient population must have been unresponsive to a primary IM hepatitis B vaccination protocol, (5) patients must be chronic dialysis patients, either on maintenance hemodialysis or continuous ambulatory peritoneal dialysis (CAPD), (6) studies that compare IM and ID hepatitis B vaccination-associated seroconversion rates, (7) results must be reported as seroconversion rates at 1–3, 6–9, 12, or 20 months post-vaccination, and (8) seroconversion (protective antibody levels) defined as >10 or ≥10?IU/L. Results: Our initial literature review yielded 113 results, of which four were included in our final review. These four prospective trials studied a combined total of 204 dialysis patients. Of these patients, 120 (59%) had received the hepatitis B vaccine intradermally, while 84 (41%) received it intramuscularly. Hepatitis B vaccination type, dose, route, and seroconversion rates were tabulated for each study. Each of the studies used different protocols for patient inclusion, schedule of vaccine administration, and time-points for measuring seroconversion. Seroconversion rates at either 1, 2, 3, 6–9, 12 and/or 20 months were reported. The combined seroconversion rates were 91%, 83%, 86%, 81%, 76%, and 32% at 1, 2, 3, 6–9, 12, and 20 months in the ID group, respectively, and 55%, 72%, 58%, 44%, 24%, and 0% in the IM group, respectively. Chi-square analysis revealed a significantly higher proportion of patients achieving seroconversion in the ID group versus the IM group (p?<?0.05). Conclusions: Our review demonstrates that ID hepatitis B vaccination in primary non-responders undergoing dialysis provides an effective alternative to IM vaccination as a means of protection against hepatitis B infection in this highly susceptible population. Additional well-designed, double-blinded, randomized trials are warranted to establish clear guidelines on ID Hepatitis B vaccine dose and duration of vaccination schedule.     

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.     

Controlled trial of thymopentin in hemodialysis patients who fail to respond to hepatitis B vaccination

Uremic patients are at high risk of hepatitis B virus (HBV) infection and, despite the availability and efficacy of hepatitis B vaccine, a high rate of non responders has been reported. Forty uremic patients undergoing maintenance hemodialysis who failed to produce any measurable anti-HBs antibody response after 4 administrations of 5 micrograms of Hevac B Pasteur vaccine were admitted to a randomized controlled clinical trial. Group A (14 patients) received 3 doses of 5 micrograms s.c. each of vaccine at monthly intervals and 12 doses of 50 mg s.c. of thymopentin on alternate days between the first and the second vaccination. Group B (11 patients) received 3 doses of 5 micrograms s.c. each of vaccine at monthly intervals. Group C (15 patients) received 3 doses of 10 micrograms s.c. each of vaccine at monthly intervals. Immunization rates were 86% in group A (on both 1-month and 6-month checks), 36% on the 1-month and 27% on the 6-month check in group B, 53% on the 1-month and 47% on the 6-month check in group C. Anti-HBs antibody titers were similar in group A and C but notably lower in group B. Thymopentin seems as useful therapeutical tool for non responder patients. As it promotes T cell maturation and responsiveness, which are impaired in uremia, it could play a major part in the management of uremic immunodeficiency.     

Complete seroconversion by low-dose intradermal injection of recombinant hepatitis B vaccine in hemodialysis patients.

The present study was undertaken to find out if the seroconversion rate of hemodialysis (HD) patients was enhanced by the intradermal (i.d.) inoculation of recombinant hepatitis B (HB) vaccine. Thirty-five HBs-Ag, HBs-Ab and HBc-Ag, HBc-Ab negative HD patients were divided into three groups: 14 patients in group I received 5 micrograms HBs Ag i.d. every 2 weeks, 13 patients in group II were given 2.5 micrograms HBs vaccine i.d. every 2 weeks, 5 times, then every week. The remaining 8 patients in group III were immunised with 10 micrograms HBs Ag every 4 weeks 5 times intramuscularly (i.m.), then 5 micrograms i.d., every 2 weeks until complete seroconversion. Antibody response to i.m. injection was poor and only 37.5% of patients developed anti-HBs at a titer of 10 mIU/ml or more at 16 weeks after the start of immunisation. However, this poor response was improved by i.d. injection. The time of seroconversion was significantly earlier and the rate of response was higher in group I. The poor response in group II was markedly improved by doubling the inoculation rate. Overall, 100% of seroconversion was finally obtained by multiple i.d. immunisation. However, the anti-HBs titers were lower in all patients and declined in some patients after the immunisation was stopped. The last seroconverted patient in each group lost protective antibody levels at the 39th week. These patients became antibody positive again at the 52nd week with a booster dose. We feel that the i.d. route remains a useful and cheaper method of obtaining prophylaxis against HBs in high-risk HD patients but it would seem to be prudent to monitor these patients serially to assess the persistence of anti-HBs in the serum.     

A new adjuvant improves the immune response to hepatitis B vaccine in hemodialysis patients

Prehemodialysis and hemodialysis patients are at an increased risk of hepatitis B infection and have an impaired immune response to hepatitis B vaccines. We evaluated the immune response to the new adjuvant of hepatitis B vaccine AS04 (HBV-AS04) in this population. We measured antibody persistence for up to 42 months, and the anamnestic response and safety of booster doses in patients who were no longer seroprotected. The primary vaccination study showed that HBV-AS04 elicited an earlier antibody response and higher antibody titers than four double doses of standard hepatitis B vaccine. Seroprotection rates were significantly higher in HBV-AS04 recipients throughout the study. The decline in seroprotection over time was significantly less in the HBV-AS04 group with significantly fewer primed patients requiring a booster dose over the follow-up period. Solicited/unsolicited adverse events were rare following booster administration. Fifty-seven patients experienced a serious adverse event during the follow-up; none of which was vaccine related. When HBV-AS04 was used as the priming immunogen, the need for a booster dose occurred at a longer time compared to double doses of standard hepatitis B vaccine. Hence, in this population, the HBV-AS04 was immunogenic, safe, and well-tolerated both as a booster dose after HBV-AS04 or standard hepatitis B vaccine priming.     

Expectation of impaired response to recombinant hepatitis B vaccination.

A controlled trial of hepatitis B vaccination with recombinant antigen was undertaken in 18 hemodialysed end-stage renal failure (ESRD) patients (P) and 16 members of our staff (controls, C). In order to identify expected nonresponders (NR), we monitored T lymphocyte (Tc) subsets, peripheral blood mononuclear cells (PBMC), total leukocytes (WBC) and IgG. After 3 vaccine doses of 40 and 20 IU, respectively, for P and C, at 0, 1 and 6 months, 11 P(61.1%) and all C (100%) responded, as in previous reports [1-3]. The 7 NR presented lower CD4+ Tc fraction, compared to responders (R) and C (p less than 0.05), and higher monocyte (p less than 0.00001) and WBC (p less than 0.002) counts, with lower lymphocyte fraction (p less than 0.001), compared to R. We suggest that NR could represent a selected group of ESRD patients, screenable by these easily detectable features, probably markers of a specific immune dysfunction.     

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.