Mycophenolate and lower graft function reduce the seroresponse of kidney transplant recipients to pandemic H1N1 vaccination

In late 2009 transplant organizations recommended that kidney recipients be vaccinated for pandemic H1N1 influenza (pH1N1); however, the vaccine efficacy was unknown. We had offered a monovalent non-adjuvanted pH1N1 vaccine to transplant recipients. Here we compared the pre- and post-vaccination seroresponses of 151 transplant recipients to that of 71 hemodialysis patients and 30 healthy controls. Baseline seroprotection was similar between groups but was significantly different at 1 month (44, 56, and 87%, respectively). Seroconversion was significantly less common for transplant recipients (32%) than dialysis patients (45%) and healthy controls (77%). After adjusting for age and gender, dialysis patients were significantly more likely (2.7-fold) to achieve new seroprotection than transplant recipients. The likelihood of seroprotection in transplant recipients was significantly reduced by mycophenolate use (adjusted odds ratio 0.24), in a dose-dependent manner, and by reduced eGFR (adjusted odds ratio 0.16 for worst to best). Seroprotection and geometric mean antibody titers increased substantially in 49 transplant recipients who subsequently received the 2010 seasonal influenza vaccine. Thus, patients requiring renal replacement therapy had reduced seroresponses to vaccination with the monovalent vaccine compared with healthy controls. Transplant recipient responses were further reduced if they were receiving mycophenolate or had significantly lower graft function.     

Durability of the hepatitis B vaccination in pediatric renal transplant recipients

Since hepatitis B virus (HBV) vaccine implementation, HBV infection has significantly decreased. However, adult renal transplant recipients show a higher rate of seroreversion compared to the general population, leading to HBV infection risk. Data are limited in pediatric renal transplant recipients. Retrospective data were collected to determine the seroprotection and durability of HBV vaccination in pediatric renal transplant patients from 2004 to 2014. One hundred subjects were categorized based on pre‐ and post‐transplant hepatitis B surface antibody (HBsAb). Pretransplant, 85 recipients (85%) had a positive HBsAb compared to 15 (15%) with negative HBsAb. In univariable analyses, other than age (P < .05) no significant differences existed pretransplant by demographics, pretransplantation dialysis, or number of vaccinations. Of the 85 pretransplantation responders, 53 (62%) remained HBsAb positive post‐transplantation, 28 (32%) seroreverted, and 4 developed indeterminate titers. All seroreversions occurred within 5 years post‐transplant. Receipt of a living donor organ had higher risk of reversion (P = .005). No significant differences were found in demographics, pretransplantation dialysis, vaccination number, or acute rejection. Despite vaccination, 15% of pediatric renal transplant candidates were seronegative, and an additional 32% lost seroprotection within 5 years post‐transplantation leaving nearly half of transplant recipients at risk for HBV infection.     

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.     

Efficacy of the accelerated hepatitis B vaccination schedule used in haemodialysis patients post-exposure to virus: a single-centre experience.

BACKGROUND: The hepatitis B (HB) vaccination regime currently recommended for use in the UK for both preventative and post-exposure purposes is the accelerated regime, although there have been no recent reports of its efficacy. This observational study reports on the response rate achieved and longevity of protection conferred with this regime in a large number of haemodialysis patients following an episode of HB exposure. METHODS: One-hundred and five patients received primary vaccination (vaccine administered at 0, 1 and 2 months). Eighty-six completed the regime, receiving a booster dose at month 12. Measuring antibodies to HB surface antigen (anti-HBS) 6 weeks after receiving the third and fourth doses assessed patients' response. Seventy-seven patients subsequently had anti-HBs measured at month 24. RESULTS: The response rate (anti-HBS >10 mIU/ml) to primary vaccination and the complete regime was 33 and 73%, respectively. Non-European patients responded better to primary vaccination than Europeans (P=0.014). Those receiving steroids responded less well to the complete vaccination regime (P=0.007). Patient's age, sex, renal diagnosis, diabetes mellitus, time on dialysis, dialysis adequacy, erythropoietin dose, hepatitis C or body weight did not affect response rates. By month 24, 24 responders (44%) had lost seroprotection. Antibody levels achieved with vaccination by transient responders was significantly lower than persistent responders. No patients became HB surface antigen positive during the 2-year study. CONCLUSION: Reserving the accelerated vaccination to the post-exposure scenario will expose many more patients to the risk of HB cross-infection than if used prophylactically. Regular monitoring is required if seroprotection is to be maintained.     

Factors Associated With H1N1 Influenza Vaccine Receipt in a High-Risk Population During the 2009-2010 H1N1 Influenza Pandemic

Background:

Persons with spinal cord injuries and disorders (SCI/D) are at high risk for respiratory complications from influenza. During pandemic situations, where resources may be scarce, uncertainties may arise in veterans with SCI/D.

Objective:

To describe concerns, knowledge, and perceptions of information received during the 2009-2010 H1N1 influenza pandemic and to examine variables associated with H1N1 vaccine receipt.

Methods:

In August 2010, a cross-sectional survey was mailed to a national sample of veterans with traumatic and nontraumatic SCI/D.

Results:

During the pandemic, 58% of veterans with SCI/D received the H1N1 vaccine. Less than two-thirds of non-H1N1 vaccine recipients indicated intentions to get the next season’s influenza vaccine. Being ≥50 years of age and depressed were significantly associated with higher odds of H1N1 vaccination. Being worried about vaccine side effects was associated with lower odds of H1N1 receipt. Compared to individuals who reported receiving an adequate amount of information about the pandemic, those who received too little information had significantly lower odds of receiving the H1N1 vaccine. Those who received accurate/clear information (vs confusing/conflicting) had 2 times greater odds of H1N1 vaccine receipt.

Conclusions:

H1N1 influenza vaccination was low in veterans with SCI/D. Of H1N1 vaccine nonrecipients, only 63% intend to get a seasonal vaccine next season. Providing an adequate amount of accurate and clear information is vital during uncertain times, as was demonstrated by the positive associations with H1N1 vaccination. Information-sharing efforts are needed, so that carry-over effects from the pandemic do not avert future healthy infection prevention behaviors.     

H1N1 vaccination in pediatric renal transplant patients

Background

Solid organ transplant recipients undergoing immunosuppressive therapy are considered to be at high risk of serious infectious complications. In 2009, a new influenza pandemic caused serious infections and deaths, especially among children and immunocompromised patients. Herein we have reported the safety and efficacy of a single-shot monovalent whole-virus vaccine against H1N1 infection in the pediatric renal transplant population.

Methods

In November and December 2009, we vaccinated 37 renal transplant children and adolescents and measured their antibody responses. Seroprotection, seroconversion, and seroconversion factors were analyzed at 21 days after vaccination.

Results

None of the vaccinated patients experienced vaccine-related side effects. None of the patients had an H1N1 influenza infection after vaccination. All of the patients showed elevations in antibody titer at 21 days after vaccination. In contrast, only 29.72% of the patients achieved a safe seroprotection level and only 18.75% a safe seroconversion rate. More intense immunosuppressive treatment displayed negative effect on seroprotection and seroconversion, and antibody production significantly increased with age. No other factor was observed to influence seroprotection.

Conclusions

We recommend vaccination of children and adolescent renal transplant recipients against H1N1 virus. However, a single shot of vaccine may not be sufficient; to achieve seroprotection, a booster vaccination and measurement of the antibody response are needed to assure protection of our patients.     

Antibody response to influenza A vaccination in children with nephrotic syndrome

The aim of this study was to determine the antibody response to influenza vaccination in children with nephrotic syndrome (NS). Nineteen children with NS and 10 healthy controls were vaccinated with a 1999–2000 influenza vaccine. A dose of 0.25 ml was used for those under 6 years and 0.5 ml for those over 6 years. All children were given two doses with a month between each dose. Antibody titers were measured before vaccination and 1 month after vaccination in both groups and 6 months after vaccination in 8 patients with NS. The proportion of subjects in the nephrotic group with protective antibody titers before immunization (10.5%) was significantly lower than the proportion at 1 (78.9%) and 6 months (87.5%) post vaccination. The mean concentration of specific IgG antibodies to influenza A in the NS group increased 6-fold at 1 month and approximately 14-fold at 6 months. These results suggest that pediatric patients with NS have an adequate antibody response to influenza A vaccine. Protective antibody titers to influenza A were maintained at 6 months after immunization in 8 patients with NS.     

Immunogenicity of low-dose MF59-adjuvanted 2009 influenza A/H1N1 vaccine in dialysis patients

Background

In response to the pandemic 2009 A/H1N1 virus, monovalent MF59-adjuvanted vaccines were prepared. Recently, single 3.75-μg doses of MF59-adjuvanted vaccines have shown good immunogenicity in young adults. However, the immunogenicity of these vaccines has not been evaluated in dialysis patients.

Methods

Dialysis patients received a single 3.75-μg dose of MF59-adjuvanted vaccine by intramuscular injection. For immunogenicity assays, serum samples were obtained before vaccination and 28 days after vaccination. All sera were tested by hemagglutination inhibition assays.

Results

Overall, 48 hemodialysis (HD) patients and 34 peritoneal dialysis (PD) patients were included in immunogenicity analysis. In HD patients, geometric mean titers (GMTs) were significantly increased compared with baseline GMTs in both young (aged 18–60 years) and elderly (aged ≥60 years) patients (51.2 ± 51.4 vs. 14.1 ± 20.7 in young patients, P = 0.012; 37.9 ± 73.9 vs. 6.8 ± 8.0 in elderly patients, P = 0.018, respectively). The rates of seroprotection and seroconversion were 27.6 and 17.2 % in young patients and 31.6 and 26.3 % in elderly patients, respectively. Among PD patients, GMTs were increased only in young patients (39.8 ± 51.4 vs. 6.8 ± 5.0, P = 0.001). The rates of seroprotection and seroconversion were 36.0 and 36.0 % in young patients and 11.1 and 0.0 % in elderly patients, respectively.

Conclusion

A single 3.75-μg dose of MF59-adjuvanted vaccine was suboptimal to elicit protective antibody response in dialysis patients. Antibody responses against vaccine were compromised especially in elderly PD patients. Trials of different vaccination protocols such as a two-dose schedule or a higher hemagglutinin antigen dose of MF59-adjuvanted vaccine are necessary for improving antibody response in dialysis patients.     

Influenza vaccination does not promote cellular or humoral activation among heart transplant recipients

BACKGROUND: The impact of influenza vaccination on in vitro parameters of cellular and humoral immunity, anti-viral titers, and clinical outcome was evaluated among cardiac transplant recipients. METHODS: Blood was collected from 29 patients before and 3-4 weeks after influenza vaccination and tested for phenotypic changes in lymphoid subpopulations and generation of antibodies against the allograft and vaccine. RESULTS: Vaccination did not change the percentage of lymphoid subpopulations and did not induce generation of anti-HLA alloantibodies. Anti-vaccine response was detected in 12 of 29 patients and did not correlate with rejection history, length of graft survival, or immunosuppressive therapy. Vaccination did not change the frequency of rejection. Flu-like symptoms were reported in one patient but not confirmed microbiologically. CONCLUSION: Despite the small number of patients in the study, influenza vaccination did not induce undesirable side effects, such as graft rejection or allo-sensitization. Generation of a positive anti-vaccine response was lower among the transplant recipients than healthy volunteers (41% vs. 80%). Clinical efficacy of the vaccine among the responders was not evaluated.     

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.     

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.     

Immune response to influenza vaccination in children with renal disease

Although immunization with influenza vaccine is recommended for children with chronic renal disease and after organ transplantation, the antibody response in these children has not been well described. We studied the response to the 1993–1994 trivalent influenza vaccine in children, aged 1–21 years, with chronic renal failure (n=15), end-stage renal disease requiring dislysis (n=10), and post renal transplantation (n=17). Each group's antibody response was compared with that of a control group (n=7). No significant differences were found in seroconversion rates, percentage of patients achieving protective hemagglutination-inhibition titers post vaccination or change in geometric mean titers from pre to post vaccination between study groups and controls. These results suggest that pediatric patients with renal disease will respond and therefore will benefit from currently recommended influenza immunization.     

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.     

The Effect of Adjuvant H1N1 Influenza Vaccine on Allograft Kidney Function

IntroductionAdministration of the adjuvant influenza vaccine has been suspected to increase the risk of allograft rejection; however, not much is known about the effect of adjuvant H1N1 vaccination on allograft kidney function. The aim of this study was to evaluate the effect of adjuvant H1N1 vaccine on allograft kidney function.MethodsA total of 78 stable kidney transplant recipients were enrolled in the study. These patients were vaccinated with a pandemic adjuvant H1N1 inactivated intramuscular influenza vaccine. Local and systemic adverse reactions occurring for 2 weeks after vaccination were recorded. Serum creatinine, creatinine clearance, and 24-hour urine proteinuria were measured before and 1 and 3 months and 2.5 years after vaccination.ResultsMean patient age was 45 ± 14 years (range, 21–78 years). Serum creatinine, creatinine clearance, and 24-hour urine proteinuria levels were not significantly different between before and 1 month after vaccination (1.3 ± 0.35 vs 1.3 ± 0.5 mg/dL, 83 ± 28 vs 78 ± 31 mL/min, and 356 ± 437 vs 293 ± 307 mg, respectively). Serum creatinine level did not differ significantly between before and 2.5 years after vaccination (1.3 ± 0.35 vs 1.4 ± 0.39 mg/dL; P > .05). No rejection episodes occurred during 2.5 years of follow-up. Reported adverse reaction frequencies included pain (20%), muscle aches (4%), fever (2.6%), and headache (1.3%).ConclusionsThe use of pandemic adjuvant H1N1 influenza vaccination is safe in patients after kidney transplantation. However, larger cohort studies with longer follow-up periods are needed to confirm this issue.     

The antibody response to pandemic H1N1 2009 influenza vaccine in adult organ transplant patients

Limited data are available regarding antibody response and the safety of the monovalent influenza A H1N1/09 vaccine for immunocompromised patients. In this study, the humoral response to this vaccine in solid organ transplant (SOT) recipients and healthy individuals was evaluated. Eighty‐two SOT recipients and 28 healthy individuals received two doses of the influenza A H1N1/09 AS03 adjuvanted vaccine containing 3.75 mg of haemagglutinin at a 3‐ to 4‐week interval. Serum samples were drawn at baseline and 3–4 weeks after the first and second vaccine doses. Seroprotective titres were measured with a haemagglutination inhibition. After the first dose seroprotective titres were observed in 69% of the SOT patients and in 96% of the healthy controls (P = 0.006), and increased after the second dose to 80% and 100%, respectively (P = 0.003). All controls and 77% of the SOT recipients achieved a ≥4‐fold titre rise after the first immunisation (P = 0.005). The vaccine was well tolerated and no acute rejection was observed. Influenza A H1N1/09 vaccine elicited a protective antibody response in the majority of SOT recipients, but the response was lower when compared with controls. A second dose significantly improved vaccine immunogenicity in SOT recipients. (ClinicalTrials.gov number: NCT01254955)     

One‐year vaccination against hepatitis B virus with a MPL‐vaccine in liver transplant patients for HBV‐related cirrhosis

Conflicting results have been reported on vaccination against hepatitis B virus (HBV) as a prophylaxis against viral recurrence after liver transplantation. We investigated the efficacy of 1‐year, monthly vaccination using an adjuvant 3‐deacylated monophosphoryl‐lipid‐A (MPL) recombinant S vaccine initially administered together with hepatitis B immunoglobulins (HBIg) in 18 patients transplanted for HBV‐related cirrhosis. All received 12 vaccine doses (HBsAg, 20 mcg plus MPL, 50 mcg): the initial six doses (phase I) were administered within 7 days after intravenous HBIg (2000 IU), while the last 6 (phase II) following HBIg withdrawal. All patients received lamivudine during the study. Anti‐HBs titers were determined before each dose and then for 1 year after vaccination. After phase I anti‐HBs titers were greater than 100 IU/l in all patients and in three (16.6%) were greater than 500 IU/l. After phase II 10 patients (55.5%) achieved anti‐HBs titers greater than 100 IU/l and five (27.7%) greater than 500 IU/l. One year after vaccination eight patients (44.4%) maintained anti‐HBs titers greater than 100 IU/l, with a median titer of 234 IU/l (102–1205), and 2 (11.1%) greater than 500 IU/l. One‐year extended monthly vaccination with a MPL‐adjuvant recombinant vaccine induces a sustained protective anti‐HBs response in approximately half of transplant recipients.     

The safety and efficacy of GM-CSF as an adjuvant in hepatitis B vaccination of chronic hemodialysis patients who have failed primary vaccination

BACKGROUND: End-stage renal disease and the need for chronic hemodialysis is an indication for hepatitis B vaccination, but up to half of dialysis patients fail to respond to a 40 microg/dose i.m. three-dose primary series of recombinant hepatitis B vaccine. Only another 10-20% respond to additional boosting doses of vaccine. PATIENTS AND METHODS: Since GM-CSF has been shown to be an effective adjuvant for hepatitis B vaccine in healthy subjects and multiple animal vaccine models, we conducted a randomized, double-blind trial of GM-CSF with recombinant hepatitis B vaccine in chronic hemodialysis patients. Patients with negative hepatitis B surface antibody and antigen who had received at least three doses of recombinant hepatitis B vaccine without response (antibody titre < 10 mIU/ml) were randomized to placebo, 40 microg, or 80 microg of GM-CSF given with 40 microg recombinant hepatitis B vaccine i.m. at the same site. Clinical and laboratory studies for safety assessment were done on days 1 and 3, and hepatitis B surface antibody titres were measured at baseline and days 21 and 180 after the study injections. RESULTS: No significant local or systemic toxicity was noted from the co-injections. The rates of response and geometric mean titre (GMT) were equivalent among all three study groups: placebo 6/10 developed antibodies, GMT 22.1 mIU/ml; 40 microg GM-CSF 3/10 developed antibodies, GMT 5.4 mIU; and 80 microg GM-CSF 3/8 developed antibodies, GMT 9.7 mIU/ml. Six months after vaccination, antibody titres were available for 11 of the 12 day 21 positive responders; only 4 of these 11 patients remained antibody positive at 6 months. CONCLUSION: GM-CSF given in a single 40 microg and 80 microg i.m. dose was not an effective adjuvant with hepatitis B vaccine in chronic hemodialysis patients who had previously failed to respond to hepatitis B immunization.     

Pandemic 2009 influenza H1N1 virus vaccination: compliance and safety in a single hemodialysis center

Background: Acceptance of vaccination against pandemic 2009 H1N1 influenza virus has been poor in some countries, perhaps because of concerns about safety of the new vaccine. Subjects and methods: We prospectively examined vaccination compliance and reasons for nonvaccination in the dialysis patients and the staff of a single hemodialysis unit, after on-site vaccination with a monovalent inactivated adjuvanted H1N1 vaccine. Safety profile was evaluated and compared to that of a control group without chronic kidney disease (CKD). Results: Vaccination acceptance among dialysis patients in our unit was 68% (110/161). Dialysis patients vaccinated against H1N1 had significantly higher compliance with vaccination for seasonal influenza and pneumococcus than those unvaccinated. Three out of 34 (9%) of the unit's staff received the vaccine. Fear of side effects was the main reason for not vaccinating in both groups, while several participants did not consider pandemic influenza a serious disease. At least one adverse reaction was observed in 37/110 (33.6%) of the vaccinated dialysis patients and in 22/42 (52.4%) of the non-CKD control group, p = 0.034. Local mild pain at injection site was the most common side effect of vaccination in both groups. All side effects were of short duration and no serious adverse reactions related to the vaccine or reactions of special interest occurred during the follow-up period. Conclusions: Our findings indicate that immunization against H1N1 virus in dialysis patients is safe and do not support the concerns about safety of the vaccine that was the main reason for nonvaccination in our study.     

Effect of levamisole supplementation on tetanus vaccination response rates in haemodialysis patients: A randomized double‐blind placebo‐controlled trial

Levamisole as an immunomodulator drug has been demonstrated to improve the immune response to hepatitis B virus vaccination in haemodialysis patients. The aim of this randomized double‐blind placebo‐controlled trial was to evaluate the effect of levamisole supplementation on tetanus‐diphtheria (Td) vaccine response rates in haemodialysis patients. Forty haemodialysis patients who had not received tetanus vaccination in a year before investigation and had unprotective anti‐tetanus immunoglobulin G (IgG) levels (<0.1 international unit/mL) were enrolled and randomized into two equal groups to receive one dose of intramuscular Td vaccine supplemented with either levamisole (100 mg) or placebo daily, for 6 days before and 6 days after vaccination. The anti‐tetanus IgG levels were measured 1 and 6 months after vaccination. One month post‐vaccination, four patients were excluded from the levamisole group and two from the placebo group because of either death or renal transplantation. At 1 month, 13 out of 16 (81%) patients in the levamisole group as compared with six out of 18 (33%) patients in the placebo group developed protective anti‐tetanus IgG levels (relative risk = 2.44, 95% confidence interval (CI) = 1.21, 4.88). From 1 to 6 months post‐vaccination, one more patient in the levamisole group and two more patients in the placebo group were excluded because of renal transplantation. At 6 months, 11 out of 15 (73%) patients in the levamisole group as compared with four out of 16 (25%) patients in the placebo group still had protective anti‐tetanus IgG levels (relative risk = 2.93, 95% CI = 1.19, 7.23). Supplementation of Td vaccination with levamisole may enhance seroconversion against tetanus in haemodialysis patients.     

Multimodal safety assessment of measles‐mumps‐rubella vaccination after pediatric liver transplantation

Live‐attenuated vaccines are currently contraindicated in solid‐organ transplant recipients. However, the risk of vaccine‐preventable infections is lifelong, and can be particularly severe after transplantation. In this prospective interventional national cohort study, 44 pediatric liver transplant recipients with measles IgG antibodies <150 IU/L (below seroprotection threshold) received measles‐mumps‐rubella vaccine (MMR) at a median of 6.3 years posttransplantation (interquartile range, 4.0 to 10.9). A maximum of two additional doses were administered in nonresponders or when seroprotection was lost. Vaccine responses occurred in 98% (95% confidence interval [CI], 88‐100) of patients. Seroprotection at 1‐, 2‐, and 3‐year follow‐up reached 62% (95% CI, 45‐78), 86% (95% CI, 70‐95), and 89% (95% CI, 67‐99), respectively. All patients responded appropriately to the booster dose(s). Vaccinations were well tolerated and no serious adverse event attributable to vaccination was identified during the 8‐week follow‐up period (or later), using a multimodal approach including standardized telephone interviews, diarized side effect reporting, and monitoring of vaccinal virus shedding. We conclude that live attenuated MMR vaccine can be administered in liver transplant recipients fulfilling specific eligibility criteria (>1 year posttransplantation, low immunosuppression, lymphocyte count ≥0.75 G/L), inducing seroprotection in most subjects. (Clinicaltrials.gov number NCT01770119).