Vaccination In Transplant Recipients Research Articles

IMMUNE RECONSTITUTION AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA PATIENTS AS A BASIS FOR EARLY VACCINATION WITH T-CELL DEPENDENT VACCINES

Minsk Study Group for Infections in Hematology, Transplantation and Cancer (MSTH). Introduction: Currently, the vaccination of transplant recipients is of particular practical importance, since in this population the incidence of vaccine-preventable infections is much higher, while the level of vaccine coverage remains low, especially in adults. Immune response to the conjugated vaccines is based on T-dependent (CD4+) activation of B-cells, which should be taken into account when estimating the recovery time of the immune system after transplantation in candidates for vaccination [1]. Timing of vaccination with T-cell dependent vaccines should be carried out with regard to reconstitution of the following B-cell levels: NvB (naive B-cells), MnSw-cells (memory non-switched B-cells), MSw-cells (memory switched B-cells), levels of dendritic cells (DC1 and DC2) and their ratio. Therefore, in this study we aimed to assess the immune reconstitution dynamics in autologous hematopoietic stem cells (auto-HSCs) transplantation patients as a basis for early vaccination with T-cell dependent vaccines. Materials and Methods: The procedure of HSCs transplantation and pre-transplant conditioning were performed according to current EBMT guidelines. The immunophenotype of peripheral blood cells was determined by the method of eight-color flow cytofluorimetry using a FACSCanto ΙΙ flow cytofluorimeter (Becton Dickinson, USA). Immunophenotyping was performed for all adult patients with multiple myeloma included in the research phase: baseline (before auto-HSCT), day +30, day +60, day +90, day +180. For statistical analysis the Kruskal-Wallis test (ANOVA) was used. Post-hoc analysis was performed by Conover test. The analysis was a part of a registered clinical study (ClinicalTrials.gov Identifier: NCT03619252). Results and Discussion: There were totally 37 adult HSCs transplant recipients included in the study, with baseline characteristics given in Table 1, all of them had multiple myeloma as a primary disease and an indication for auto-HSCT.In the studied sample, starting from the 30th day, the level of CD4+ was above 200 cells/μl in all patients (Fig. 2), which indicates the effectiveness of early vaccination with T-dependent vaccines in patients after auto-HSCT [2]. Levels of naive B-cells returns to the initial value by the 60th day after transplantation (Kruskal-Wallis test 41.97; 4 d.f.; p<0.001), Fig. 2. Dendritic cells recover as early as the 30th day from autologous transplantation, both DC1 and DC2 (Kruskal-Wallis test 25.78; 4 d.f.; p<0.001 for DC-1 cells and Kruskal-Wallis test 11.17; 4 d.f.; p<0.025, respectively), Fig. 3-4.Conclusion: Observed immunological reconstitution rates in patients after autologous HSCT may serve as a basis for early vaccination start (at 60 days after HSCT) with T-cell dependent vaccines, including, but not limited to conjugate vaccines.

Awareness of Inadvertent Use of Yellow Fever Vaccine Among Recipients of Renal Transplant

Yellow fever (YF) is a vaccine-preventable disease, but live attenuated YF vaccine (YFV) is contraindicated in immunosuppressed patients due to the risk of life-threatening YFV-associated side effects.This study aimed to evaluate 1. the knowledge of renal transplant recipients (RTRs) about the contraindication and risks of YFV; 2. the prevalence of inadvertent vaccination of RTRs against YF; and 3. the outcome of these patients. A cross-sectional telephone contact study was conducted with 200 RTRs selected from the outpatient clinic of our transplantation unit.There were 116 successful telephone contacts (58%). A total of 11 vaccinated patients were identified: 5 received YFV in the pretransplant period and 6 in the post-transplant period. All patients received the full dose of the vaccine. Among those vaccinated after transplant, only 1 reported a mild adverse event (nausea) after receiving the vaccine. All vaccinated patients who were post-transplant did not know about vaccine contraindications as a result of their clinical condition. Among the unvaccinated patients, this rate was 12.4%.YFV is the main tool for disease prevention and control as there is no specific antiviral treatment for YF. Our results confirm the evidence that transplant recipients tolerate YFV well. However, data are not strong enough to recommend this vaccine in transplant recipients. Counseling RTRs on the contraindications of YFV is important to prevent inadvertent use of this vaccine in this population.

Sex-Specific Differences in HLA Antibodies after Pneumococcal Vaccination in Kidney Transplant Recipients.

In transplant recipients vaccination against Streptococcus pneumoniae is recommended to reduce mortality from invasive pneumococcal disease. It is still debated if vaccination in transplant recipients triggers alloresponses. Therefore, it was our aim to define if vaccination with Prevenar 13®, a 13-valent, conjugated pneumococcal vaccine (Pfizer, New York, NY, USA) that acts T cell dependently, induces human leukocyte antigen (HLA) antibodies in clinically stable kidney transplant recipients. Forty-seven patients were vaccinated once with Prevenar 13® and HLA antibodies were determined prior to vaccination and at month 1 and 12 thereafter. In parallel, pneumococcal IgG antibodies were measured. Using Luminex™ Mixed Beads technology (One Lambda/Thermo Fisher, Canoga Park, CA, USA) we observed overall no change in HLA antibodies after vaccination. Pneumococcal antibodies increased significantly at month 1 (p < 0.0001) and remained elevated at month 12 (p < 0.005). A more detailed analysis of HLA antibodies showed that in 18 females HLA class I and II antibodies increased significantly at month 1 and 12 (p < 0.05); whereas in 29 males HLA class I and II antibodies tended to decrease. Using Luminex™ Single Antigen Beads assay, no de novo donor-specific HLA antibodies were detected after vaccination. In conclusion, the current data indicate that females may be more susceptible to the induction of (non-specific) HLA antibodies after vaccination.

Is there evidence for efficacy of human papillomavirus vaccination in solid organ transplant recipients?

Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections worldwide and is associated with precancerous lesions and cancers of the cervix, vulva, vagina, penis, anus, tonsils and base of the tongue. Several studies show an increased risk of HPV-associated cancers in solid organ transplant recipients (SOTR). The aims of this review are to investigate the evidence of efficacy for the HPV vaccination in transplant recipients and to discuss the known national guidelines. A systematic literature search has been conducted to identify studies where SOTR received the HPV vaccination to evaluate the efficacy of the HPV vaccine on this population. The primary outcome was antibody response against the HPV genotypes included in the vaccines and the secondary outcome was national guidelines recommending HPV vaccination of SOTR. Three cohort studies evaluated immunogenicity. Two studies found suboptimal effect of the HPV vaccine, while an early terminated study detected 100% seropositivity. We have identified four national guidelines in the following countries; United States of America, Canada, Australia and Ireland, along with a recommendation from the World Health Organization (WHO).The results from the three studies were inconclusive due to the small sample sizes and the diverging results. Recommendations of HPV vaccination of SOTR is based on the knowledge about safety and efficiency in the general population and the safety of other inactivated (not live) vaccines in SOTR. Theoretically, the nonavalent vaccine should be recommended as the first choice in SOTR without age- or sex restrictions.

Immunogenicity and safety of double versus standard dose of the seasonal influenza vaccine in solid-organ transplant recipients: A randomized controlled trial

BackgroundThe use of vaccines with higher doses of antigen is an attractive strategy to improve the immunogenicity of influenza vaccination in transplant recipients. However, the effect of vaccination with a double-dose (DD) containing 30 µg of antigen in this population remains unknown. MethodsWe performed a randomized controlled trial to compare the immunogenicity and safety of DD (30 µg) vs. standard dose (SD, 15 µg) of a trivalent inactivated influenza vaccine in kidney and liver transplant recipients. Immunogenicity was assessed by hemagglutination-inhibition assay. Vaccine response was defined as seroconversion to at least one viral strain 2 weeks after vaccination and seroprotection as a titer ≥40. ResultsSixty-three kidney and 16 liver transplant recipients were enrolled. Forty patients received the DD and 39 the SD vaccine. Overall, 40% of patients in the DD compared to 26% in the SD group (P = 0.174) responded to vaccine. In the DD arm, more patients were seroprotected to all viral strains after vaccination (88% vs 69%, P = 0.048). Post vaccination geometric mean titers of antibodies were 131.9 vs. 89.7 (P = 0.187) for H1N1, 185.4 vs. 138.7 (P = 0.182) for H3N2, and 96.6 vs. 68.8 (P = 0.081) for influenza B with the DD vs. SD. In both groups, most of the adverse events were mild and no vaccine-related severe adverse events were observed. ConclusionDouble-dose influenza vaccine is safe and may increase antibody response in transplant recipients. In this population, DD vaccination could be an alternative when high-dose vaccine is not available. NCT02746783.

Influenza vaccine strategies for solid organ transplant recipients.

The aim of this study was to highlight recent evidence on important aspects of influenza vaccination in solid organ transplant recipients. Influenza vaccine is the most evaluated vaccine in transplant recipients. The immunogenicity of the vaccine is suboptimal after transplantation. Newer formulations such as inactivated unadjuvanted high-dose influenza vaccine and the administration of a booster dose within the same season have shown to increase response rates. Intradermal vaccination and adjuvanted vaccines did not show clear benefit over standard influenza vaccines. Recent studies in transplant recipients do not suggest a higher risk for allograft rejection, neither after vaccination with a standard influenza vaccine nor after the administration of nonstandard formulation (high-dose, adjuvanted vaccines), routes (intradermally) or a booster dose. Nevertheless, influenza vaccine coverage in transplant recipients is still unsatisfactory low, potentially due to misinterpretation of risks and benefits. Annual influenza vaccination is well tolerated and is an important part of long-term care of solid organ transplant recipients.

Discrepant serological assays forPneumococcusin renal transplant recipients - a prospective study

Vaccine immunoprotection for Streptococcus pneumoniae is mediated by opsonizing antibodies targeting serotype-specific capsular polysaccharides. Quantitative antibody levels enzyme-linked immunosorbent assay (ELISA) and antibody-mediated opsonophagocytic assays (OPA) measure vaccine-induced protection; correlation of these assays in transplantation requires investigation. This study examines the laboratory assessment of antibody titers in vaccinated renal recipients. Streptococcus pneumoniae 19A is common in immunocompromised hosts and is represented in protein-conjugate vaccines (PCV) and polysaccharide vaccines (PSV). Antibodies to 19A in serial sera from 30 vaccinated renal transplant recipients were compared using ELISA and OPA assays. Subject titers were classified as protected or not by ELISA (>0.35 μg/ml) and OPA titer (>1:8). Antibody titers analyzed using McNemar's test indicate that protection measured by the two assays are not the same (P = 0.0078); simple linear regression of within-subject geometric means of 19A enzyme-linked immunosorbent assay (ELISA) antibody levels versus 19A opsonophagocytic assays (OPA) titers demonstrates significant correlation between the two assays (P < 0.001). Vaccination is increasingly important given increasing antimicrobial resistance worldwide. OPA and ELISA antibody assays do not correlate well using current values for protective immunity against the Pneumococcus in immunosuppressed transplant recipients. Future studies of vaccination in transplant recipients should evaluate protective antibody levels using both functional antibody assays and standard ELISA antibody titers. (ClinicalTrials.gov: NCT00307125).

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.

Donor-Specific Alloantibody Upregulation After Influenza Vaccination in Transplant Recipients

Donor-Specific Alloantibody Upregulation After Influenza Vaccination in Transplant Recipients

Influenza Vaccination in the Organ Transplant Recipient: Review and Summary Recommendations

Influenza virus causes a spectrum of illness in transplant recipients with a high rate of lower respiratory disease. Seasonal influenza vaccination is an important public health measure recommended for transplant recipients and their close contacts. Vaccine has been shown to be safe and generally well tolerated in both adult and pediatric transplant recipients. However, responses to vaccine are variable and are dependent on various factors including time from transplantation and specific immunosuppressive medication. Seasonal influenza vaccine has demonstrated safety and no conclusive evidence exists for a link between vaccination and allograft dysfunction. Annually updated trivalent inactivated influenza vaccines have been available and routinely used for several decades, although newer influenza vaccination formulations including high-dose vaccine, adjuvanted vaccine, quadrivalent inactivated vaccine and vaccine by intradermal delivery system are now available or will be available in the near future. Safety and immunogenicity data of these new formulations in transplant recipients requires investigation. In this document, we review the current state of knowledge on influenza vaccines in transplant recipients and make recommendations on the use of vaccine in both adult and pediatric organ transplant recipients.

Vaccination of SCT recipients

Last year several scientific organizations collaborated in drafting the guidelines for prevention of infections after hematopoietic SCT (HSCT).1, 2 One set of guidelines dealt with vaccination of transplant recipients and in these guidelines the conjugated heptavalent pneumococcal vaccine (PCV7; Prevnar; Pfizer Inc.) was recommended based on several studies showing both immunogenicity and safety of this vaccine in HSCT recipients. Earlier this year, a 13-valent vaccine (Prevnar13; Pfizer Inc., New York, NY, USA), which is produced in a similar way to the 7-valent vaccine, was licensed in both the USA and Europe after the completion of large clinical trials in healthy children. This vaccine contains the same seven pneumococcal serotype antigens contained in the PCV7 together with antigens from additional six serotypes. After licensure, it was decided that the heptavalent vaccine will be withdrawn from the market and therefore the published recommendations cannot be followed. Presently, a clinical trial is ongoing with this 13-valent vaccine in allogeneic HSCT recipients. In addition, a 10-valent pneumococcal vaccine (Synflorix; GlaxoSmithKline, London, UK) conjugated to another carrier protein has also been licensed in Europe for which no data yet exist in immunocompromised patients. The alternative to these conjugated vaccines is polysaccharide vaccines that have shown decreased immunogenicity compared with conjugate vaccines in allogeneic HSCT recipients. Despite the lack of data, we recommend that the 13-valent vaccine be used as replacement for the heptavalent vaccine when this is no longer available, until additional studies are performed.

Efficacy and safety of measles, mumps, rubella and varicella live viral vaccines in transplant recipients receiving immunosuppressive drugs

This review was designed to summarize published data on the efficacy and safety of live viral vaccines for measles, mumps, rubella, or varicella in post-transplant patients currently on immunosuppression. Medline, EMBASE and Evidence Based Medicine Reviews were searched from 1966 to November 2007 for case reports or studies describing the efficacy and/or safety of live attenuated measles, mumps, rubella, or varicella vaccine in children on immunosuppression following solid organ, bone marrow or stem cell transplantation. The review identified 6 case series and 2 case reports describing 114 solid organ transplant recipients and one case series describing 27 bone marrow transplant recipients who had received a combined total of 206 doses of live varicella, measles, mumps, or rubella vaccine while on immunosuppression. Post-immunization titers were in the immune range in 109 of the 171 situations where they were measured following a single dose of vaccine (64%) and in 15 of 22 situations following 2 doses (68%). There were no major safety concerns in this small sample. There are insufficient published data to derive evidence-based guidelines for use of live viral vaccines in transplant recipients on immunosuppression but preliminary data on efficacy and safety suggest that the use of these live viral vaccines in transplant recipients still on immunosuppression could be a reasonable strategy.

Augmentation of post transplant immunity: antigen encounter at the time of hematopoietic stem cell transplantation enhances antigen-specific donor T-cell responses in the post transplant repertoire

After transplant, the immune system is reconstituted by cells derived from both hematopoietic stem cells and peripheral expansion from differentiated donor T cells. After transplant, immune function is poor despite transplantation of mature lymphocytes from immune-competent donors. We tested the hypothesis that early antigen encounter at the time of cell transplant would improve the desired donor T-cell responses. Two independent models of peptide-specific T-cell responses were studied. The model for CD4 cells employed T cells from transgenic (Tg) DO11.11 mice that constitutively express the T-cell receptor for the class II-restricted ovalbumin peptide 323-339. The model for CD8 cells employed non-Tg H2-Db-restricted T-cell responses to the influenza nucleoprotein peptide 366-374. As measured both functionally and by direct imaging of T cells using clonotypic reagents, encounter with specific antigen at the time of T-cell transplantation led to clonal expansion of donor T cells and preservation of donor T-cell function in the post transplant immune environment. Antigen-specific donor T-cell function was poor if antigen encounter was delayed or omitted. Severe parent>F1 graft-versus-host reactions blocked the effect of early antigen exposure. Vaccination of transplant recipients against microbial or leukemia antigens may be worthy of study.

Efficacy and safety of vaccination of marrow transplant recipients with a live attenuated measles, mumps, and rubella vaccine.

Long-term immunity to measles, mumps, and rubella viruses was studied in 57 patients after allogeneic bone marrow transplantation. Among patients who were seropositive at the time of transplant, 51% had retained antibodies to measles, 42% had retained antibodies to mumps, and 76% had retained antibodies to rubella 2 y later. There was no difference in the ability to retain antibodies to these viruses between patients with and those without chronic graft-versus-host disease (GVHD). Twenty seronegative patients without active chronic GVHD or ongoing immunosuppressive treatment were vaccinated with a live attenuated trivalent vaccine against measles, mumps, and rubella. No early or late side effects were detected after the vaccinations. The percentages of patients who seroconverted after vaccination were 77%, 64%, and 75% for measles, mumps, and rubella, respectively. Vaccination of transplant recipients with a live attenuated vaccine against measles, mumps, and rubella is safe and usually effective 2 y after transplant if the patients do not have active chronic GVHD or ongoing immunosuppressive treatment at the time of vaccination.