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.     

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.     

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.     

Evaluation of immune responses to seasonal influenza vaccination in healthy volunteers and in patients after stem cell transplantation

BACKGROUND: Influenza causes significant morbidity and mortality in immunocompromised stem cell transplantation (SCT) recipients. Measurement of cellular and humoral immunological responses might increase our understanding of how to estimate a protective response to influenza vaccination. METHODS: Eighteen healthy subjects and 14 SCT patients tested before and 4 weeks after influenza vaccination were included in the study. Peripheral blood lymphocytes were stimulated with influenza peptides and Enzyme-Linked ImmunoSpot assays to measure the production of intracellular interferon-gamma, interleukin-4 and interleukin-13. Prelabeled major histocompatibility complex class I pentamers were used for the detection of influenza-specific CD8+ T-cells. B-cell Enzyme-Linked ImmunoSpot and hemagglutination inhibition assays were performed to enumerate influenza-specific antibody-secreting cells and titer of neutralizing antibodies. RESULTS: Influenza vaccination elicited strong cell-mediated immune responses in the healthy controls (P< or =0.003 for all four peptides) and SCT patients (P< or =0.008). The percentage of CD8+ specific cells increased significantly after vaccination both in volunteers (P=0.005) and in patients (P< or =0.003). The number of influenza-specific antibody-secreting cells increased after vaccination both in volunteers (P=0.009) and in patients (P=0.01). Twenty-nine percent of SCT patients demonstrated protective antibody levels to influenza A H1/N1 serotype. CONCLUSIONS: Seasonal vaccination against influenza boosts the cellular immune response both in SCT patients and healthy controls. The protective effect is lower in the patients in general and especially on those, vaccinated early after SCT.     

Safety and efficacy of two types of influenza vaccination in heart transplant recipients: a prospective randomised controlled study.

BACKGROUND: Influenza may cause severe disease in immunosuppressed patients. Different vaccines have been proved to be efficacious to prevent influenza in tranplant recipients. Since the last five years the addition of adjuvants to improve the immune response to vaccine preparations has been proposed and evaluated. In this study, two antigenically identical vaccines, but different for the presence of adjuvants were randomised among a cohort of heart transplant recipients to evaluate their safety and immunogenicity. METHODS: 58 patients, receiving an heart transplant more than 6 months before, were randomised to receive one shoot vaccination with Fluad (containing the MF59 adjuvant) or Agrippal (no adjuvant added) or to enter the control, not-vaccinated, group. The immune response to influenza was evaluated separately for type A and type B viruses and for the IgG and the IgM antibodies. Patients were clinically evaluated at least monthly up to 6 months. RESULTS: Influenza symptoms were reported by 33% of patients receiving Fluad, 29% of the Agrippal and 63% of the control group. 4 episodes of acute myocardial rejection >/=3A were identified without difference between the three groups. CONCLUSIONS: The superior efficacy of vaccines containing adjuvants was not found and the data clearly confirmed that vaccination against influenza is safe and effective in heart transplant recipients. The use of vaccine containing adjuvant substances do not ameliorate the clinical performance of the immunisation suggesting that less expensive influenza vaccine preparation without adjuvant substances could be equally useful to protect heart transplant recipients.     

Humoral response to natural influenza infection in solid organ transplant recipients

The humoral immune response of transplant recipients to influenza vaccination has been studied in detail. In contrast, the hemagglutinin inhibiting (HI) antibody response evoked by natural influenza infection and its impact on viral kinetics is unknown. In this prospective, multicenter, cohort study of natural influenza infection in transplant recipients, we measured HI antibody titers at presentation and 4 weeks later. Serial nasopharyngeal viral loads were determined using a quantitative influenza A polymerase chain reaction (PCR). We analyzed 196 transplant recipients with influenza infection. In the cohort of organ transplant patients with influenza A (n = 116), seropositivity rates for strain‐specific antibodies were 44.0% (95% confidence interval [CI] 31.5‐53.2%) at diagnosis and 64.7% (95% CI 55.4‐72.9%) 4 weeks postinfection. Seroconversion was observed in 32.8% (95% CI 24.7‐41.9%) of the cases. Lung transplant recipients were more likely to seroconvert (P = .002) and vaccine recipients were less likely to seroconvert (P = .024). A subset of patients (n = 30) who were unresponsive to prior vaccination were also unresponsive to natural infection. There was no correlation between viral kinetics and antibody response. This study provides novel data on the seroresponse to influenza infection in transplant patients and its relationship to a number of parameters including a prior vaccination status, virologic measures, and clinical variables.     

Influenza vaccine antibody responses in lung transplant recipients

CONTEXT: Lung transplant recipients are at high risk of morbidity and mortality from influenza infection because of altered lung physiology and immunosuppression. Annual influenza immunization is recommended, but the ability to mount an antibody response may be limited by immunosuppressant medications. OBJECTIVE: To compare the antibody response rate to influenza vaccine in lung transplant recipients to healthy controls. DESIGN: Open label study. SETTING: Lung transplant clinic and General Clinical Research Center at a university hospital. SUBJECTS: Sixty-eight single and bilateral lung transplant recipients and 35 healthy controls were enrolled in October and November 2002. METHODS: Each individual underwent blood sampling before receiving the 2002-2003 influenza vaccine and 4 weeks later. Influenza antibody concentrations were measured by hemagglutination inhibition assay. Vaccine response rates (antibody concentration >40 hemagglutination units and at least 4-fold increase in antibody concentration) were compared using chi2. The influence of specific immunosuppressants on vaccine response was compared. RESULTS: The influenza vaccine response rate for lung transplant recipients was 29/68 (43%) and 22/35 (63%) for the healthy individuals (P < .05; chi2). Among the recipients, mycophenolate mofetil was associated with poorer influenza vaccine antibody response (> 40 hemagglutination units) (62% vs 91%; P = .01), whereas sirolimus (91% vs 63%; P = .02) was associated with better influenza antibody response compared to those not taking mycophenolate mofetil or sirolimus, respectively. CONCLUSION: Lung transplant recipients had lower influenza vaccine response rates than healthy individuals. Influenza vaccine antibody response is influenced by concomitant administration of mycophenolate mofetil or sirolimus. Future studies should measure protection from influenza infection conferred by immunization and alternative vaccination strategies.     

Impairment of the immune response to influenza vaccination in renal transplant recipients by cyclosporine, but not azathioprine

Influenza vaccination has been strongly recommended for immunosuppressed renal transplant recipients. However, immunosuppression may lead to impaired antibody responses. We studied the antibody response to an inactivated trivalent influenza vaccine in 59 renal transplant recipients with life-sustaining kidney function: 21 were on cyclosporine and prednisone, 38 on azathioprine and prednisone. Healthy volunteers (n = 29) and patients on hemodialysis (n = 28) served as controls. Despite comparable renal allograft function, cyclosporine-treated patients had a significantly lower immune response against influenza A viruses than azathioprine-treated patients, whether mean antibody levels, fourfold titer rise, or seroconversion to protective titers was analyzed. No significant differences in antibody responses were found between healthy controls and patients on azathioprine. The patients on hemodialysis showed an impaired response to vaccination. However, in contrast to the cyclosporine-treated patients, booster immunization proved valuable in this group.     

Alternative strategies of posttransplant influenza vaccination in adult solid organ transplant recipients

Solid organ transplant (SOT) recipients are at increased risk of influenza disease and associated complications. The mainstay of prevention is the annual standard-dose influenza vaccine, as studies showed decreased influenza-related morbidity and mortality in vaccinated SOT recipients compared to those unvaccinated. Nonetheless, the immune response in this high-risk population is suboptimal compared to healthy individuals. Over the past two decades, several vaccination strategies have been investigated to overcome this inadequate immune response in SOT recipients. Howbeit, the best vaccination strategy and optimal timing of influenza vaccination remain unclear. This review will provide a detailed summary of studies of various influenza vaccination strategies in adult SOT recipients, discussing immunogenicity results, and addressing their limitations and knowledge gaps.     

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.     

Influenza Virus Infection in Adult Solid Organ Transplant Recipients

BACKGROUND: Solid organ transplant (SOT) recipients have been reported to be more susceptible to influenza virus. However, little is known about the clinical epidemiology and the implications of influenza viral infection among SOT recipients. METHODS: Cohort study of influenza viral infection in SOT recipients at the University of Pittsburgh Medical Center. RESULTS: Between November 1990 and April 2000, 30 cases of influenza were diagnosed in SOT recipients at our center, including influenza A (n = 22) and influenza B (n = 8). These included recipients of lung (n = 19), liver (n = 5) and kidney (n = 6) transplants. The incidence of influenza viral infection was 41.8 cases/1,000 person years (PYs), 2.8 cases/1000 PYs and 4.3 cases/ 1,000 PYs among lung, liver and renal transplant patients, respectively (p <0.0001). Symptoms were reported in all patients and included malaise, myalgia/ arthralgia, fever, cough, and shortness of breath. Secondary bacterial pneumonia occurred in five patients (17%). Other complications were seen in three SOT recipients (2 liver and 1 kidney) and included: myocarditis, myositis, and bronchiolitis obliterans. Biopsy of the transplanted organ was performed in 21 SOT recipients (18 lung, 1 liver and 2 kidney) at the time of influenza viral infection. Overall, 62% (13/21) showed variable degrees of acute allograft rejection, and included 61% (11/18) of lung, and 100% (2/2) of kidney transplant recipients. CONCLUSIONS: Influenza infection is associated with significant morbidity in different groups of SOT recipients. Studies are needed to determine if yearly chemoprophylaxis with antiviral drugs might benefit this patient population.     

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.     

Panel Reactive Antibody Responses Against Influenza Vaccination in Kidney Transplant Recipients

IntroductionSeasonal influenza is an important cause of morbidity and mortality in the post-transplant period; therefore, the influenza vaccination has been recommended for all kidney transplant recipients before the influenza season. However, at least theoretically, the introduction of antigens via vaccines may trigger rejection attacks by causing an antibody response. In this study, we examined the development of de novo panel reactive antibody (PRA) development against the influenza vaccine in kidney transplant recipients.Materials and MethodsOverall, 41 kidney transplant recipients who received the influenza vaccination and 50 kidney transplant recipients (study group) who refused to receive the influenza vaccination (control group) were enrolled in the study. Following basal biochemistry examination, the inactivated trivalent influenza vaccine was administered intramuscularly. Panel reactive antibodies were screened in all patients before and after vaccination on days 30 and 180. The primary outcome variable was development of de novo panel reactive antibodies.ResultsOne patient in the study group developed de novo class I and II PRA at 6 months after vaccination (P > .05), while no antibody development was noted in the control group. Graft dysfunction or biopsy-confirmed rejection was not observed during the follow-up period in both groups.ConclusionThe influenza vaccination is generally effective and safe in solid organ transplant recipients. The vaccination procedure has the potential to trigger antibody development and occurrence of rejection. Therefore, vaccinated kidney transplant recipients should be monitored more carefully with regard to PRA; if the graft deteriorates, a rapid transplant biopsy should be performed.     

Influenza and parainfluenza respiratory viral infection requiring admission in adult lung transplant recipients

BACKGROUND: Although influenza and parainfluenza viruses commonly cause respiratory tract infections in the community, their incidence and clinical implications in adult lung transplant recipients have received little attention. METHODS: We performed a retrospective cohort study of influenza and parainfluenza viral infections in adult lung transplant recipients at the University of Pittsburgh Medical Center. RESULTS: Between January 1989 and March 1999, 39 cases (single-lung 25, double-lung 14) of influenza or parainfluenza respiratory viral infection were identified at a mean of 1.7 years (SD+/-1.4) after transplantation. The mean length of admission was 7 days. The cases included 15 patients with influenza (A, 11; B, 4) and 24 with parainfluenza (para1, 7; para2, 2; para3, 15). The median age at diagnosis was 48 years; there were 19 females and 20 males. Symptoms were reported in 30 patients and lasted for a median of 7 days before admission. These included cough (64%), shortness of breath (56%), and temperature elevation (33%). Chest infiltrates were seen in 14 (36%) patients, and 5 (13%) of them required intubation and mechanical ventilation. Viral pneumonia was diagnosed in 10 (5 influenza and 5 parainfluenza) patients, and concurrent bacterial pneumonia occurred in 4 patients. Transbronchial biopsy was performed in 36 patients, of whom 23 (64%) showed some degree of acute allograft rejection. CONCLUSION: Influenza and parainfluenza respiratory viral infections are associated with significant morbidity in adult lung transplant recipients. Active vaccination programs and the development of new antiviral agents active against these viruses are important for prevention.     

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.     

Significance of monocytic cytokines at single cell level for the immune responsiveness in renal transplant recipients

Cytokine dysregulation is an important factor underlying the immune unresponsiveness to hepatitis B vaccination (HBV) in renal transplant recipients. This study investigated the relationship between monocyte-derived interleukin-6 (IL-6) and interleukin-10 (IL-10) production and the immune responsiveness using flow cytometry (cytoflow) after whole blood culture. According to their previous response to hepatitis B vaccination, 40 renal transplant recipients were divided into two groups of 20 patients. The percentage of CD 14+ monocytes stained positive for intracellular IL-6 or IL-10 was measured using flow cytometry after 4 and 20 h of whole blood culture with lipopolysaccharide stimulation. The percentage of CD 14+/IL-6+ cells after incubation in vitro for 4 h was lower in the responders compared to the non-responders and controls (27.15+/-8.93 vs 35.47+/-9.95, P=NS; and 37.06+/-10.89, P<0.05 respectively). The staining intensity of IL-6 at 4 h for responders was also significantly reduced. At 20 h, there were a significantly higher percentage of CD 14+/IL-10+ positive cells in the responders compared to the non-responders (41.87+/-18.39 vs 27.55+/-17.25, P<0.05). These results indicate that alteration of intracellular cytokine profile in activated monocytes distinguishes the HBV vaccination responders from the non-responders among renal transplant recipients. The capacity to upregulate monocyte IL-10 production in this subset of patients may modulate the immune responsiveness and effectively assists in mounting a positive response to HBV vaccination.     

Heterologous Immune Responses to Influenza Vaccine in Kidney Transplant Recipients

Influenza vaccine is known to have suboptimal immunogenicity in transplant recipients. Despite this, influenza vaccine may have the added benefit of inducing a cross‐reactive immune response to viral strains not found in the vaccine. This is termed “heterologous immunity” and has not been assessed previously in transplant patients. Pre‐ and postvaccination sera from kidney transplant recipients (n = 60) immunized with the 2012–2013 adjuvanted or nonadjuvanted influenza vaccine underwent testing by hemagglutination inhibition assay for strains not present in vaccine: A/New Caledonia/20/99 (H1N1), A/Texas/50/2012 (H3N2) and B/Brisbane/60/2008. The geometric mean titer of antibody to heterologous strains increased after vaccine (H1N1: 80.0 to 136.1, p < 0.001; H3N2: 23.3 to 77.3, p < 0.001; B: 13.3 to 19.5, p < 0.001). Seroconversion rates were 16.7%, 41.7%, and 13.3%, respectively. No differences in heterologous response were seen in the adjuvanted versus nonadjuvanted groups. Patients were more likely to seroconvert for a cross‐reactive antigen if they seroconverted for the specific vaccine antigen. Seroconversion to heterologous A/H3N2, for example, was 84.0% for homologous H3N2 seroconverters versus 11.4% for nonseroconverters (p < 0.001). This study provides novel evidence that transplant recipients are able to mount significant cross‐protective responses to influenza vaccine that may be an additional, previously unknown benefit of immunization.     

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.     

Immune status assessment in adult lung transplant candidates

BackgroundLung transplant recipients have an increased susceptibility to a variety of infections due to immunosuppressive therapy. Current guidelines recommend pneumococcal and other vaccinations, prior to lung transplantation to protect against post-transplant infections, but measurement of the antibody response to vaccination is not advised. Immune status investigation in lung transplant candidates, including the response to pneumococcal polysaccharide vaccination, has not been described.MethodsImmune status investigation, including measurement of immunoglobulins, complement and the response to 23-valent pneumococcal polysaccharide vaccination (23vPPV) was performed in 81 adult lung transplant candidates.ResultsEighteen patients had low IgG levels and 32 patients had low IgG1 and/or IgG2 levels. After vaccination with 23vPPV the median antibody concentration of all serotypes increased significantly. Fifty-two patients had protective IgG-post-vaccination antibody levels to at least 10 serotypes. Twenty-nine patients had an impaired response to 23vPPV.ConclusionsIn conclusion, a significant proportion of our cohort of lung transplant candidates had one or more abnormalities in the immune status. It is likely that these patients have an increased risk for infections after transplantation. Revaccination, including measurement of antibody response, and possibly antibody replacement therapy should be considered to minimize infection risk.     

Immunogenicity and Safety of an Intradermal Boosting Strategy for Vaccination Against Influenza in Lung Transplant Recipients

The immunogenicity of influenza vaccine is suboptimal in lung transplant recipients. Use of a booster dose and vaccine delivery by the intradermal rather than intramuscular route may improve response. We prospectively evaluated the immunogenicity and safety of a 2-dose boosting strategy of influenza vaccine. Sixty lung transplant recipients received a standard intramuscular injection of the 2006-2007 inactivated influenza vaccine, followed 4 weeks later by an intradermal booster of the same vaccine. Immunogenicity was assessed by measurement of geometric mean titer of antibodies after both the intramuscular injection and the intradermal booster. Vaccine response was defined as 4-fold or higher increase of antibody titers to at least one vaccine antigen. Thirty-eight out of 60 patients (63%) had a response after intramuscular vaccination. Geometric mean titers increased for all three vaccine antigens following the first dose (p < 0.001). However, no significant increases in titer were observed after the booster dose for all three antigens. Among nonresponders, 3/22 (13.6%) additional patients responded after the intradermal booster (p = 0.14). The use of basiliximab was associated with a positive response (p = 0.024). After a single standard dose of influenza vaccine, a booster dose given by intradermal injection did not significantly improve vaccine immunogenicity in lung transplant recipients.