Humoral Response After SARS-CoV-2 Vaccination in Kidney Transplant Recipients: Role of Immunosuppression Therapy

BackgroundMessenger RNA vaccination against COVID-19 has been shown to produce an immune response with sufficient efficacy to prevent natural infection in immunocompetent recipients. However, the response in kidney transplant recipients is low. We aimed to evaluate the specific humoral response to SARS-CoV-2 after vaccination in a population of kidney transplant recipients and assess the main factors associated with a lack of response.MethodsWe undertook a prospective study of 105 kidney transplant recipients and 11 recipients of a combined kidney-pancreas transplant. We analyzed immunoglobulin G and immunoglobulin M antibodies after the patients received their second and third doses of the messenger RNA 1273 (Moderna) or BNT162b1 (BionTECH-Pfizer) vaccinations between February and November 2021.ResultsMean (SD) age of the 116 patients was 50 (16) years, and 65% were men. They had their transplants for 40 months (IQR, 15-123 months), with 14% undergoing retransplant and 11% sensitized. The maintenance immunosuppression regimen was steroids + tacrolimus + mycophenolate (MMF) in 68% of the patients and any combination with mammalian target of rapamycin inhibitor (mTORi) in 28%. A humoral response developed in 40% of the patients 6 weeks (IQR, 4-10 weeks) after receiving the second dose of the vaccine. Of the 67 patients with no response to the second dose, 51 had an analysis of the humoral response after the third dose, which was positive in 16 (31%). A total of 80% received the Moderna vaccine and 20% the BionTECH-Pfizer. No patient experienced major adverse effects after the vaccination.Factors associated with a lack of humoral response to the vaccine were recipient age (odds ratio [OR], 1.02; 95% CI, 1.001-1.05; P = .04), diabetes (OR, 2.8; 95% CI, 1.2-6.9; P = .02), and treatment with MMF (OR, 2.6; 95% CI, 1.08-6.8; P = .03). Treatment with mTORi was associated with a better response to vaccination (OR, 0.3; 95% CI, 0.1-0.9; P = .04).ConclusionsThe humoral response to the COVID-19 vaccine in kidney transplant recipients is poor. Factors related with this lack of immunity are recipient age and diabetes, plus MMF therapy, whereas mTORi therapy was associated with a better response to vaccination.     

The Trajectory of the COVID-19 Vaccine Antibody Titers Over Time and the Association of Mycophenolate Mofetil in Solid Organ Transplant Recipients

The COVID-19 vaccine will be safe and effective in solid organ transplant recipients (SOTs). However, the blunted antibody responses were also of concern. Few studies have reported prolonged serologic follow-up after 2 doses of BNT162b2 vaccine in SOTs. We performed a single-center, prospective observational study of 78 SOTs who received 2 doses of BNT162b2 vaccine. We identified the trajectory of antibody titers after vaccination among SOTs with or without mycophenolate mofetil (MMF) or withdrawn from MMF. We found low seroconversion rates (29/42: 69%) and low antibody titers in SOTs treated with MMF. An inverse linear relationship between neutralizing antibody titers and MMF concentration was confirmed in restricted cubic spline plots (P for effect < .01, P for nonlinearity = .08). For the trajectory of antibody responses, seroconversion and improved antibody titers were observed after withdrawal from MMF in SOTs who showed seronegative or low antibody titers at the first visit after 2 doses of vaccine (P for effect < .01, P for nonlinearity < .05, and P for interaction < .01). We identified increased B-cell counts after withdrawal from MMF (P < .01). The recovery of antibody responses was seen in SOTs withdrawn from MMF. The trajectories of antibody responses were modified by MMF administration.     

Dialysis modality,humoral response to vaccine,and SARS-CoV-2 infection risk: Comparative prospective evaluation

Background

COVID-19 vaccinations have a central role in decreasing severe SARS-CoV-2 disease complications. This study investigated the long-term humoral immune response to BNT162b2 vaccine among hemodialysis (HD) versus peritoneal dialysis (PD) patients, and their relative risk for COVID-19 infection.

Methods

This prospective, observational study included maintenance HD and PD patients who had received at least two BNT162b2 vaccine doses. Levels of antibodies targeting SARS-CoV-2 spike protein were measured 6 and 12 months after the first vaccine dose, and 2–3 weeks after the third and fourth vaccine doses. Patients were divided according to dialysis modality (HD or PD). Humoral response was evaluated at different time points among different vaccine regimens (two vs. three vs. four doses of vaccine). An adjusted multivariate model was used to assess cumulative risk for SARS-CoV-2 infection.

Results

Eighty-seven HD and 36 PD patients were included. Among them, 106 (86%) received at least three vaccine doses. Both HD and PD patients demonstrated marked increases in humoral response 2–3 weeks after the third dose (mean anti-S antibody increased from 452 ± 501 AU/mL to 19,556 ± 14,949 AU/mL, p < 0.001). By 6 months after the third dose, antibody titers had declined significantly (mean anti-S antibody 9841 ± 10,493 AU/mL, p < 0.001). HD patients had higher risk for SARS-CoV-2 infection than PD patients (OR 4.4 [95% CI 1.4–13.6], p = 0.006). In multivariate analysis, the most important predictor for SARS-CoV-2 infection was dialysis modality.

Conclusion

This study found a high antibody response rate after the third and fourth doses of BNT162b2 vaccine among dialysis patients. Hemodialysis as dialysis modality is an important predictor of COVID-19 infection, despite similar humoral responses to vaccine in peritoneal dialysis.     

Serologic response to a third dose of an mRNA-based SARS-CoV-2 vaccine in lung transplant recipients

Lung transplant recipients have an increased risk for severe coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A third dose of a SARS-CoV-2 vaccine has been recommended for all solid organ transplant recipients, but data from lung transplant recipients specifically are scarce. In this study, the serologic response to a third dose of an mRNA-based SARS-CoV-2 vaccine was measured in 78 lung transplant recipients. Sixty-two percent (n = 48) had a serological response to vaccination, which was significantly higher than after the second vaccine dose (27 patients (35%); p = 0.0013). A positive serologic response was associated with having had COVID-19 (p = 0.01), and higher serum IgG level and complement mannose binding lectin pathway activity prior to vaccination (p = 0.04 and p = 0.03, respectively). Serologic response was not associated with the dose of mycophenolate mofetil or prednisone or other immune status parameters. Eleven patients (14%) developed COVID-19 after the second or third vaccine dose, but this did not associate with serologic response after the second vaccine dose (9% in patients who developed COVID-19 versus 39% in patients who did not develop COVID-19 (p = 0.09)), or with serologic response above cut-off values associated with clinical protection in previous studies. In conclusion, the response to mRNA-based SARS-CoV-2 vaccines in lung transplant recipients improves significantly after a third vaccine dose. Factors associated with a positive serologic response are having had COVID-19 prior to vaccination, and serum IgG and complement mannose binding lectin pathway activity prior to vaccination. Serologic response did not associate with clinical protection against COVID-19 in this study.     

Efficacy and safety of a fourth dose of the COVID-19 vaccine in kidney transplant recipients: A systematic review and meta-analysis

BackgroundKidney transplant recipients (KTRs) who become infected with SARS-CoV-2 are at greater risk of serious illness and death than the general population. To date, the efficacy and safety of the fourth dose of the COVID-19 vaccine in KTRs have not been systematically discussed.MethodsThis systematic review and meta-analysis included articles from PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, and Wanfang Med Online published before May 15, 2022. Studies evaluating the efficacy and safety of a fourth dose of the COVID-19 vaccine in kidney transplant recipients were selected.ResultsNine studies were included in the meta-analysis, with a total of 727 KTRs. The overall pooled seropositivity rate after the fourth COVID-19 vaccine was 60% (95% CI, 49%–71%, I² = 87.83%, p > 0.01). The pooled proportion of KTRs seronegative after the third dose that transitioned to seropositivity after the fourth dose was 30% (95% CI, 15%–48%, I² = 94.98%, p < 0.01).ConclusionsThe fourth dose of the COVID-19 vaccine was well tolerated in KTRs with no serious adverse effects. Some KTRs showed a reduced response even after receiving the fourth vaccine dose. Overall, the fourth vaccine dose effectively improved seropositivity in KTRs, as recommended by the World Health Organization for the general population.     

Weak antibody response to three doses of mRNA vaccine in kidney transplant recipients treated with belatacept

Poor responses to mRNA COVID-19 vaccine have been reported after 2 vaccine injections in kidney transplant recipients (KTRs) treated with belatacept. We analyzed the humoral response in belatacept-treated KTRs without a history of SARS-CoV-2 infection who received three injections of BNT162b2-mRNA COVID-19 vaccine. We also investigated vaccine immunogenicity in belatacept-treated KTRs with prior COVID-19 and characterized symptomatic COVID-19 infections after the vaccine in belatacept-treated KTRs. Among the 62 belatacept-treated KTRs (36 [58%] males), the median age (63.5 years IQR [51–72]), without COVID-19 history, only four patients (6.4%) developed anti-SARS-CoV-2 IgG with low antibody titers (median 209, IQR [20–409] AU/ml). 71% were treated with mycophenolic acid and 100% with steroids in association with belatacept. In contrast, in all the 5 KTRs with prior COVID-19 history, mRNA vaccine induced a strong antibody response with high antibody titers (median 10 769 AU/ml, IQR [6410–20 069]) after two injections. Seroprevalence after three-vaccine doses in 35 non-belatacept-treated KTRs was 37.1%. Twelve KTRs developed symptomatic COVID-19 after vaccination, including severe forms (50% of mortality). Breakthrough COVID-19 occurred in 5% of fully vaccinated patients. Administration of a third dose of BNT162b2 mRNA COVID-19 vaccine did not improve immunogenicity in KTRs treated with belatacept without prior COVID-19. Other strategies aiming to improve patient protection are needed.     

Serologic response to COVID-19 infection or vaccination in pediatric kidney transplant recipients compared to healthy children

BackgroundDifferences in serologic response to COVID-19 infection or vaccination were reported in adult kidney transplant recipients (KTR) compared to non-immunocompromised patients. This study aims to compare the serologic response of naturally infected or vaccinated pediatric KTR to that of controls.MethodsThirty-eight KTR and 42 healthy children were included; aged ≤18 years, with a previously confirmed COVID-19 infection or post COVID-19 vaccination. Serological response was measured by anti-spike protein IgG antibody titers. Response post third vaccine was additionally assessed in KTR.ResultsFourteen children in each group had previously confirmed infection. KTR were significantly older and developed a 2-fold higher antibody titer post-infection compared to controls [median (interquartile range [IQR]) age: 14.9 (7.8, 17.5) vs. 6.3 (4.5, 11.5) years, p = 0.02; median (IQR) titer: 1695 (982, 3520) vs. 716 (368, 976) AU/mL, p = 0.03]. Twenty-four KTR and 28 controls were vaccinated. Antibody titer was lower in KTR than in controls [median (IQR): 803 (206, 1744) vs. 8023 (3032, 30,052) AU/mL, p < 0.001]. Fourteen KTR received third vaccine. Antibody titer post booster in KTR reached similar levels to those of controls post two doses [median (IQR) 5923 (2295, 12,278) vs. 8023 (3034, 30,052) AU/mL, p = 0.37] and to KTR post natural infection [5282 AU/mL (2583, 13,257) p = 0.8].ConclusionSerologic response to COVID-19 infection was significantly higher in KTR than in controls. Antibody level in KTR was higher in response to infection vs. vaccination, contrary to reports in the general population. Response to vaccination in KTR reached levels comparable to controls only after third vaccine.     

Evaluation of the Correlation Between Responders and Non-Responders to the Second Coronavirus Disease Vaccination In Kidney Transplant Recipients: A Retrospective Single-Center Cohort Study

BackgroundThe immune response to COVID-19 vaccination in kidney transplant (KTx) recipients is significantly lower than that in healthy controls. We evaluated immune responses after the COVID-19 vaccine and their possible relationship with other cofactors in KTx recipients.MethodsThis retrospective single-center cohort study included 29 KTx recipients 2-8 weeks after receiving 2 doses of the Pfizer-BioNTech SARS-CoV-2 messenger RNA vaccine. Anti-SARS-CoV-2 spike (S) immunoglobulin (Ig)-G levels were evaluated to define cofactors influencing the immune response between the responder (anti-SARS-CoV-2 IgG level ≥0.8 U/mL) (n = 16) and nonresponder groups (anti-SARS-CoV-2 IgG level <0.8 U/mL) (n = 13). The kinetics of antibodies between 2 and 6 months after the second vaccination was also compared between the groups.ResultsKTx recipients with IgG levels ≥0.8 U/mL were younger (54 [interquartile range {IQR}, 46.5-61] years vs 65 [IQR, 55-71.5] years; P = .01), had been transplanted for a longer median time (1588 [IQR, 1382-4751] days vs 1034 [IQR, 548.5-1833] days; P = .02), and were more often treated with a lower mycophenolate mofetil dosage (765.6 ± 119.6 vs 1077 ± 76.9 mg; P = .04) than KTx recipients with IgG levels <0.8 U/mL. There was no significant difference in antibody titers between time periods after the second dose in the responder group. At the 6-month follow-up, a serologic response against the SARS-CoV-2 S was observed in 44.4% of KTx recipients in the nonresponder group.ConclusionsMore than 50% of KTx recipients developed a higher antibody response after the second dose of COVID-19 vaccination.     

Humoral response after SARS-CoV-2 mRNA vaccination in patients with prostate cancer using steroids

ObjectivesThe effect of concomitant steroid use on the antibody response to a SARS-CoV-2 vaccine in patients with prostate cancer (PC) remains unknown. We aimed to evaluate the rates of antispike immunoglobulin G (IgG) antibody response to the BNT162b2 mRNA vaccine in patients with PC using steroids.MethodsThis cross-sectional study conducted from June 21, 2021 to January 5, 2022 included 215 patients with PC who received the second dose of the BNT162b2 mRNA vaccine at least 7 days before the measurement of titers of IgG antibodies against the receptor-binding domain of SARS-CoV-2 spike (S) protein. We compared the rate of anti-SARS-CoV-2 S IgG ≥15 U/mL between patients with or without concomitant steroid use.ResultsOf 215, we identified 33 patients who had concomitant steroid use. Of these, 12 and 21 patients were metastatic castration-sensitive PC and castration-resistant PC (CRPC), respectively. Patients with concomitant steroid use had a significantly lower rate of antibody titer ≥15 U/mL than those without steroid use (82% vs. 95%, P = 0.021). Patients with CRPC with concomitant steroid use (n =21) also had a lower rate of antibody titer ≥15 U/mL (71%) than those without steroid use (93%, P = 0.051), although this was not statistically different. Increased number of systemic treatments administered after diagnosis of CRPC (3 lines or more) were significantly associated with antibody titers <15 U/mL (97% vs. 77%, P <0.001).ConclusionThe humoral response to the BNT162b2 mRNA vaccine was significantly lower in patients with concomitant steroid use. Anti-SARS-CoV-2 S antibody titers were affected by CRPC status, the accumulation of post-CRPC treatments, and steroid use.     

Analysis of Risk Factors for a Low Immune Response to Messenger RNA COVID-19 Vaccine in Kidney Transplant Recipients and Differences Between Second and Third Dose

BackgroundThe efficacy of the response to SARS-CoV-2 vaccination in kidney transplant recipients is low. The aim of our study was to evaluate the risk factors correlated with the low antibody response and whether there was an improvement between the second and the third dose.MethodsA prospective study was conducted on 176 kidney transplant recipients who received the second and the third dose of the anti-SARS-CoV-2 mRNA Comirnaty vaccine. We evaluated the seroconversion process after administration of the second and the third dose and assessed a possible correlation with age, time between transplant and vaccination, and type of immunosuppressive therapy.ResultsA total of 98 of the 176 patients (55.7%) responded positively after the inoculation of the second dose and according to the multivariable logistic regression analysis the lack of seroconversion was independently associated with patient age ≥60 (P = .025; odds ratio [OR], 2.094), time since transplant of 1 to 3 months (P = .032; OR, 2.118), and triple therapy (P = .044; OR, 2.327). After the vaccine third dose, the seroconversion increased to 62.5%, and it was negatively influenced by calcineurin inhibitor use (12/21, 57.1% vs 71/78, 91.0%, P = .0006) and triple therapy (13/21, 61.9% vs 72/78, 92.3%, P = .0014). The median of antispike antibody response significantly increased from 18.5 IU/mL after the second dose to 316.9 IU after the third dose (P < .0001).ConclusionsWe demonstrated a correlation between older age and shorter distance from the transplant and triple immunosuppressive therapy with the lack of seroconversion. We noticed a significant improvement in antibody response by a third dose of messenger RNA vaccine.     

Development of donor specific antibodies after SARS-CoV-2 vaccination in kidney and heart transplant recipients

This study examined the development of new or changes in donor specific antibodies (DSA) mean-fluorescence intensity (MFI) after SARS-CoV-2 vaccination in 100 kidney and 50 heart transplant recipients. The study was performed when the Center for Disease Control and Prevention (CDC) recommended two doses of Pfizer/BioNTech [BNT162b2] and Moderna [mRNA-1273 SARS-CoV-2] vaccine or 1 dose Johnson & Johnson/Janssen [Ad26.COV2·S] vaccines for full vaccination in transplant recipients. A novel assay bead-based platform for detecting antibodies against 4 domains of the SARS-CoV-2 spike protein to determine vaccine response (SA) and one nucleocapsid protein (NC) to determine prior SARS-CoV-2 infection was utilized. These assays were performed on the multiplex, bead-based platform utilized to assay DSA levels. 61/150 patients (40.7%) had successful vaccination. 18 patients had confirmed SARS-CoV-2 infection based on positive NC assay or previous Covid-19 oropharyngeal swab. 138 patients had no DSA prior to vaccination but 3 heart recipients developed new DSA's. Among 12 patients with known DSA prior to vaccination, 4 developed new DSA's or increased MFI. All 7 patients with new or increased DSA had stable graft function without rejection and had no changes in immunosuppression. All 8 patients with stable post vaccine DSA had stable graft function and immunosuppression was not changed. The presence of DSA before vaccination was associated with subsequent development of increased MFI or new DSA's (p = 0.001). There was no association between pre-vaccine DSA and positive vaccine response (NS). There was no association with successful vaccination or prior SARS-CoV-2 infection and DSA changes (NS).     

Safety and Tolerability of mRNA COVID-19 Vaccines in Kidney Transplant Recipients

BackgroundCOVID-19 mRNA vaccines have demonstrated excellent short-term safety in phase 3 trials. However, no kidney transplant recipients (KTR) were included. The aim of the study was to assess the safety and tolerability of COVID-19 mRNA vaccines in KTR.Materials and MethodsA longitudinal controlled study was conducted in 300 KTR and 143 control patients (CRL) without chronic kidney disease who had received 2-dose vaccinations with the mRNA vaccine. Solicited local and systemic reactogenicity and unsolicited adverse events were assessed with a standardized questionnaire. The toxicity grading scales were derived from the FDA guidelines.ResultsKTR (62.7% men) with a median (interquartile range) age of 53 (41-63) and transplant vintage of 7.25 (3-13) years did not differ with respect to age and sex distribution from CRL. One hundred percent CRL and 83.3% KTR were vaccinated with BNT162b2 (BionTech/Pfizer); 16.7% KTR received mRNA-1273 (Moderna) vaccine. Any local reactions were present in 84.7% (first dose) and 65.3% (second dose) KTR vs 67.1% and 60.1% CRL within 7 days after the vaccination. Any systemic reactions were reported by 26.7% (first dose) and 20.9% (second dose) KTR vs 24.7 and 35.7% CRL. The most common systemic reactions in KTR were fatigue, headache and myalgia. No serious adverse events were observed. Many systemic reactions were observed less frequently in KTR than CRL. Younger KTR (<54 years) reported any local and any systemic reactions significantly more frequently than older patients.ConclusionmRNA COVID-19 vaccines are safe and well-tolerated by KTR. The results may resolve patients' doubts and reduce their vaccine hesitancy.     

SARS-CoV-2 mRNA vaccination is not associated with the induction of anti-HLA or non-HLA antibodies

BackgroundSARS-CoV-2 vaccination is strongly recommended in kidney transplant recipients (KTR) and dialysis patients. Whether these vaccinations may trigger alloantibodies, is still debated.MethodsIn the current study we evaluated the effect of SARS-CoV-2 mRNA vaccines on anti-Human Leukocyte Antigen (HLA) and 60 anti-non-HLA antibody profiles in clinically stable KTR and dialysis patients. In total, we included 28 KTR, 30 patients on haemodialysis, 25 patients on peritoneal dialysis and 31 controls with a positive seroresponse 16–21 days after the first dose of either the SARS-CoV-2 mRNA BNT162b2 or mRNA-1273 vaccine. Both anti-HLA and anti-non-HLA antibodies were determined prior to vaccination and 21 to 35 days after the second vaccine dose.ResultsOverall, the proportion of patients with detectable anti-HLA antibodies was similar before and after vaccination (class I 14% vs. 16%, p = 0.48; class II 25% before and after vaccination). After vaccination, there was no pattern in 1) additionally detected anti-HLA antibodies, or 2) the levels of pre-existing ones. Additional anti-non-HLA antibodies were detected in 30% of the patients, ranging from 1 to 5 new anti-non-HLA antibodies per patient. However, the clinical significance of anti-non-HLA antibodies is still a matter of debate. To date, only a significant association has been found for anti-non-HLA ARHGDIB antibodies and long-term kidney graft loss. No additionally developed anti-ARHGDIB antibodies or elevated level of existing anti-ARHGDIB antibodies was observed.ConclusionThe current data indicate that SARS-CoV-2 mRNA vaccination does not induce anti-HLA or anti-non-HLA antibodies, corroborating the importance of vaccinating KTR and dialysis patients.     

Comparison of Humoral Response in Kidney Transplant Recipients and Donors and Healthy Volunteers Following Second Dose of SARS-CoV-2 mRNA Vaccine

PurposeTo investigate the kinetics and durability of anti-spike glycoprotein (S) immunoglobulin G (IgG) after the second dose of mRNA-based SARS-CoV-2 vaccine in kidney transplant recipients (recipients) compared with those in kidney donors (donors) and healthy volunteers (HVs) and identify factors negatively associated with SARS-CoV-2 vaccine effectiveness in recipients.MethodsWe enrolled 378 recipients with no history of COVID-19 and no anti-S-IgG before the first vaccine and who received a second mRNA-based vaccine dose. Antibodies were detected using an immunoassay more than 4 weeks after the second vaccine dose. Anti-S-IgG <0.8, ≥0.8 to 15, and ≥15 U/mL were considered negative, weak positive, and strongly positive, respectively, whereas anti–nucleocapsid protein IgG was negative. Anti-S-IgG titer was determined in 990 HVs and 102 donors.ResultsAnti-S-IgG titers were 154, 2475, and 1181 U/mL in the recipient, HV, and donor groups, respectively, with values significantly lower in recipients. The anti-S-IgG-positivity rate of recipients gradually increased following the second vaccination, suggesting that recipients had a delayed response compared with the HV and donor groups, who had a 100% positivity rate at an earlier time point. Anti-S-IgG titers decreased in donors and HVs, whereas they remained stable in recipients, although at a significantly lower level. Independent negative factors associated with anti-S-IgG titers in recipients were age >60 years and lymphocytopenia (odds ratio: 2.35 and 2.44, respectively).ConclusionsKidney transplant recipients demonstrate delayed and attenuated responses, with lower SARS-CoV-2 antibody titers after the second dose of the mRNA-based COVID-19 vaccine.     

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.     

COVID-19 Vaccines in Pancreatic Transplant Recipients: A Single-Center Observative Study

The SARS-CoV-2 pandemic was a real test of doctors’ abilities to adapt and respond to patients’ needs. The course of infection varied from influenza-like symptoms to severe infections with multi-organ failure and death. Therefore, the possibility of vaccination against the COVID-19 virus brought great hope.Since 2004, 240 pancreas and pancreas with kidney (simultaneous pancreas and kidney transplantation, pancreas after kidney, pancreas transplants alone) transplants were performed in our center. Currently, 130 transplant patients are under the care of the transplant clinic. All patients were informed about the possibility of vaccination against SARS-CoV-2 with the mRNA vaccine.The aim of the study was to evaluate the development of antibodies to SARS-CoV-2 in patients who had previously undergone transplantation. Fifty-three patients were vaccinated with the full double dose and 37 patients received an additional third dose.The level of antibodies in the IgM and IgG classes was assessed in patients’ serum. The level of antibodies was assessed before administration of the vaccine and then after administration of the first and second doses.Most patients had no response to vaccination after 1 dose of the vaccine and 21 patients achieved therapeutic antibody levels after the full dose of vaccination. However, the highest titer of immunoglobulins was found in recipients who received the third dose.The use of vaccinations is safe and can protect the group of patients after pancreas transplantation from serious complications of SARS-CoV-2 infection despite the use of immunosuppressive drugs.     

Varicella‐Zoster Immunization in Pediatric Liver Transplant Recipients: Safe and Immunogenic

Varicella can have a severe course in immunosuppressed patients. Although prevention is fundamental, live‐attenuated varicella‐zoster (VZV) vaccine is not currently recommended in transplant recipients. Our aims were to (1) evaluate VZV immunity in pediatric liver transplant (LT) recipients; (2) immunize (two doses) seronegative patients post‐LT; (3) monitor vaccine safety, (4) assess B and T cell vaccine responses. All patients followed at the Swiss National Pediatric LT Center were approached and 77/79 (97.5%) were enrolled (median age 7.8 years). Vaccine safety was monitored by standardized diary cards and phone calls. VZV‐specific serology and CD4⁺ T cells were assessed before and after immunization. Thirty‐nine patients (51.1%) were seronegative including 14 children immunized pre‐LT. Thirty‐six of 39 seronegative patients were immunized post‐LT (median 3.0 years post LT). Local (54.8%) and systemic (64.5%) reactions were mild and transient. The frequency of VZV‐specific CD4⁺ T cells and antibody titers increased significantly (respectively from 0.085% to 0.16%, p = 0.04 and 21.0 to 1134.5 IU/L, p < 0.001). All children reached seroprotective titers and 31/32 (97%) patients assessed remained seroprotected at follow‐up (median 1.7 years). No breakthrough disease was reported during follow‐up (median 4.1 years). Thereby, VZV vaccine appears to be safe, immunogenic and provide protection against disease in pediatric LT patients.     

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.     

Occurrence of Severe SARS-CoV-2 Infection in Fully Vaccinated Solid Organ Transplant Recipients

The present study presents the clinical outcome of SARS-CoV-2 disease in relation to the humoral response in fully vaccinated solid organ transplant (SOT) recipients. Our patient cohort consists of 455 SOT recipients, vaccinated with one of the 2 approved mRNA vaccines. The antibody response was measured 1 month after the second dose, and previously infected patients have been excluded. Of the 449 remaining patients, 15 (3.34%) tested positive, using SARS-CoV-2 polymerase chain reaction. Their mean age was 43.7 ±14.4 years, and median time from transplantation was 7.8 years (1.2-30.2). Eleven patients (73.3%) had been vaccinated with BNT162b2 and 4 (26.7%) with the mRNA1273 vaccine. At the time of infection 9 (60%) patients had a negative (<50 AU/mL) antibody titer, and 6 (40%) had a positive one (>50 AU/mL). Median antibody titer, 27.4± 14.0 days after the second dose, measured at 13 AU/mL (0-7480 AU/mL). Renal function did not appear to be affected by the disease. Τhe mean estimated glomerular filtration rate at diagnosis was 48 ± 15 mL/min, and when in a 29-day (1-101) median follow-up was 53.9± 20.9 mL/min. Of the 15 patients, 7 had mild symptoms and were not hospitalized, and of the remaining 8 (53.3%) who needed hospitalization 7 had severe disease and 2 of them expired. The study confirms the variable and often severe course of coronavirus 2019 infection in SOT recipients, even after their full vaccination, highlighting the need to vaccinate their close relatives and to accelerate the implementation of the booster dose of vaccine.     

Varicella zoster virus serostatus before and after kidney transplantation, and vaccination of adult kidney transplant candidates

In recent years we observed 3 lethal primary varicella infections in adult kidney transplant recipients. Therefore, we wondered how many of our adult renal transplant patients were not protected against varicella zoster virus (VZV), and therefore were at risk for such a primary infection. We also studied the prevalence of VZV seronegativity in the adult patients on our waitlist for kidney transplantation. Finally, we vaccinated these seronegative patients with an attenuated live vaccine. Sera were obtained from 854 transplanted patients, and from 286 candidates on the waitlist for kidney transplantation. We observed that 2.1% of our renal transplant recipients and 3.2% of the patients on the waitlist were seronegative for VZV. We vaccinated 11 seronegative patients on the waitlist twice without side effects. In 7 of 11 patients this resulted in a positive serologic response. In conclusion, the prevalence of VZV seronegativity was low both in renal transplant recipients (2%) and in patients on the waitlist (3%). Vaccination of transplant candidates resulted in a moderate efficiency of 64%.