Temporary antimetabolite treatment hold boosts SARS-CoV-2 vaccination–specific humoral and cellular immunity in kidney transplant recipients

JCI Insight, Год журнала: 2022, Номер 7(9)

Опубликована: Март 29, 2022

Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from patients with autoimmune disorders suggest that temporary MPA hold might greatly improve booster vaccination outcomes. We applied a fourth dose of vaccine to 29 kidney transplant during (5 weeks) MPA/azathioprine hold, who had not mounted humoral immune response previous vaccinations. Seroconversion until day 32 was observed in 76% patients, associated acquisition virus-neutralizing capacity. Interestingly, 21/25 (84%) calcineurin inhibitor-treated responded, but only 1/4 belatacept-treated responded. In line responses, counts and relative frequencies spike receptor binding domain-specific (RBD-specific) B cells were markedly increased on 7 increase RBD-specific CD27++CD38+ plasmablasts. Whereas overall proportions spike-reactive CD4+ T remained unaltered the dose, positively correlated specific IgG levels. Importantly, antigen-specific proliferating Ki67+ vivo-activated programmed cell death 1-positive significantly revaccination whereas cytokine production memory differentiation unaffected. summary, antimetabolite augmented all arms vaccination. These further studies recipients.

Язык: Английский

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Serological Response to Three, Four and Five Doses of SARS-CoV-2 Vaccine in Kidney Transplant Recipients

Journal of Clinical Medicine, Год журнала: 2022, Номер 11(9), С. 2565 - 2565

Опубликована: Май 4, 2022

Mortality from COVID-19 among kidney transplant recipients (KTR) is high, and their response to three vaccinations against SARS-CoV-2 strongly impaired. We retrospectively analyzed the serological of up five doses vaccine in KTR 27 December 2020 until 31 2021. Particularly, influence different dose adjustment regimens for mycophenolic acid (MPA) on fourth vaccination was analyzed. In total, 4277 1478 patients were Serological 19.5% after 1203 basic immunizations, increased 29.4%, 55.6%, 57.5% 603 third, 250 fourth, 40 fifth vaccinations, resulting a cumulative rate 88.7%. with calcineurin inhibitor MPA maintenance immunosuppression, pausing adding 5 mg prednisolone equivalent before 75% comparison no (52%) or reduction (46%). Belatacept-treated had 8.7% (4/46) 12.5% (3/25) four vaccinations. Except belatacept-treated patients, repeated times effectively induces recipients. It can be enhanced by at time vaccination.

Язык: Английский

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COVID-19 vaccination and breakthrough infections in patients with cancer

Annals of Oncology, Год журнала: 2021, Номер 33(3), С. 340 - 346

Опубликована: Дек. 24, 2021

Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination possible risk breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history cancer those on active immunosuppression (including chemotherapy), limited evidence available inform the efficacy across spectrum cancer. We describe features who developed compare weighted outcomes contemporary unvaccinated patients, after adjustment for confounders, using data from multi-institutional Cancer Consortium (CCC19). Patients develop have substantial comorbidities present even lethal harboring hematologic malignancies are over-represented among vaccinated remains essential strategy protecting vulnerable populations, including infection despite full vaccination, however, remain at outcomes. A multilayered public mitigation approach that includes close contacts, boosters, social distancing, mask-wearing should be continued foreseeable future.

Язык: Английский

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A Fourth Dose of COVID-19 Vaccine Does Not Induce Neutralization of the Omicron Variant Among Solid Organ Transplant Recipients With Suboptimal Vaccine Response

Transplantation, Год журнала: 2022, Номер 106(7), С. 1440 - 1444

Опубликована: Апрель 4, 2022

Background. Humoral responses to coronavirus disease 2019 (COVID-19) vaccines are attenuated in solid organ transplant recipients (SOTRs), necessitating additional booster vaccinations. The Omicron variant demonstrates substantial immune evasion, and it is unknown whether vaccine doses increase neutralizing capacity versus this of concern (VOC) among SOTRs. Methods. Within an observational cohort, 25 SOTRs with low seroresponse underwent anti–severe acute respiratory syndrome 2 spike receptor-binding domain immunoglobulin (Ig)G testing using a commercially available multiplex ELISA before after fourth COVID-19 dose (D4). Surrogate neutralization (percent angiotensin-converting enzyme inhibition [%ACE2i], range 0%–100% >20% correlating live virus neutralization) was measured against full-length proteins the strain 5 VOCs including Delta Omicron. Changes IgG level %ACE2i were compared paired Wilcoxon signed-rank test. Results. Anti–receptor-binding anti-spike seropositivity increased post-D4 from 56% 84% 68% 88%, respectively. Median (interquartile range) antibody significantly 42.3 (4.9–134.2) 228.9 (1115.4–655.8) World Health Organization binding units. (median [interquartile range]) also (5.8% [0%–16.8%] 20.6% [5.8%–45.9%]) (9.1% [4.9%–12.8%] 17.1% [10.3%–31.7%]), yet poor, did not (4.1% [0%–6.9%] 0.5% [0%–5.7%]), lower than boosted healthy controls. Conclusions. Although increases many VOCs, some may remain at high risk for infection despite boosting. Thus, protective interventions or alternative vaccination strategies should be urgently explored.

Язык: Английский

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Reduced Immune Response to Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in a Cohort of Immunocompromised Patients in Chile

Clinical Infectious Diseases, Год журнала: 2022, Номер 75(1), С. e594 - e602

Опубликована: Март 7, 2022

Abstract Background Inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been widely implemented in low- and middle-income countries. However, immunogenicity immunocompromised patients has not established. Herein, we aimed to evaluate immune response CoronaVac vaccine these patients. Methods This prospective cohort study included 193 participants with 5 different immunocompromising conditions 67 controls, receiving doses of 8–12 weeks before enrollment. The was conducted between May August 2021, at Red de Salud UC-CHRISTUS, Santiago, Chile. Neutralizing antibody (NAb) positivity, total anti–SARS-CoV-2 immunoglobulin G (TAb) concentrations, T-cell responses were determined. Results NAb positivity median neutralizing activity 83.1% 51.2% for the control group versus 20.6% 5.7% (both P < .001) solid organ transplant group, 41.5% 19.2% .0001) autoimmune rheumatic diseases 43.3% (P 21.4% (P<.01 or = cancer tumors 45.5% 28.7% human immunodeficiency virus (HIV) infection 64.3% 56.6% differences significant) hematopoietic stem cell respectively. TAb seropositivity also lower (20.6%; .0001), (61%; .001), HIV groups (70.9%; .003), compared (92.3%). On other hand, number interferon γ spot-forming T cells specific SARS-CoV-2 tended be all but did differ significantly groups. Conclusions Diverse markedly reduce humoral vaccine. These findings suggest that a boosting vaccination strategy should considered vulnerable Clinical Trials Registration NCT04888793.

Язык: Английский

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The risk and consequences of breakthrough SARS-CoV-2 infection in solid organ transplant recipients relative to non-immunosuppressed controls

American Journal of Transplantation, Год журнала: 2022, Номер 22(10), С. 2418 - 2432

Опубликована: Июнь 8, 2022

Язык: Английский

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Humoral and cellular response of COVID‐19 vaccine among solid organ transplant recipients: A systematic review and meta‐analysis

Transplant Infectious Disease, Год журнала: 2022, Номер 24(6)

Опубликована: Авг. 4, 2022

We aimed to analyze the humoral and cellular response standard booster (additional doses) COVID-19 vaccination in solid organ transplantation (SOT) risk factors involved for an impaired response.We did a systematic review meta-analysis of studies published up until January 11, 2022, that reported immunogenicity vaccine among SOT. The study is registered with PROSPERO, number CRD42022300547.Of 1527 studies, 112 which 15391 SOT 2844 healthy controls, were included. showed low (effect size [ES]: 0.44 [0.40-0.48]) overall control (log-Odds-ratio [OR]: -4.46 [-8.10 -2.35]). was highest liver (ES: 0.67 [0.61-0.74]) followed by heart 0.45 [0.32-0.59]), kidney 0.40 [0.36-0.45]), kidney-pancreas 0.33 [0.13-0.53]), lung (0.27 [0.17-0.37]). dose 0.43 [0.39-0.47] vs. 0.51 [0.43-0.54]) marginal increase 18% efficacy. prior infection had higher 0.94 [0.92-0.96] ES: [0.39-0.41]; p-value < .01). seroresponse mRNA-12723 mRNA 0.52 (0.40-0.64). Mycophenolic acid (OR: 1.42 [1.21-1.63]) Belatacept 1.89 [1.3-2.49]) nonresponse. parallelly decreased 0.42 [0.32-0.52]) -3.12 [-0.4.12 -2.13]).Overall, develops suboptimal compared general population. Immunosuppression including mycophenolic acid, belatacept, tacrolimus associated response. Booster doses immune response, but further upgradation strategy required.

Язык: Английский

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Stopping of Mycophenolic Acid in Kidney Transplant Recipients for 2 Weeks Peri-Vaccination Does Not Increase Response to SARS-CoV-2 Vaccination—A Non-randomized, Controlled Pilot Study

Frontiers in Medicine, Год журнала: 2022, Номер 9

Опубликована: Июнь 10, 2022

Introduction Kidney transplant recipients (KTR) are at high risk of developing severe COVID-19. However, vaccine response in this population is severely impaired with humoral rates 36–54 and 55–69% after two or three doses SARS-COV-2 vaccines, respectively. Triple immunosuppression specifically the use anti-proliferative agents such as mycophenolic acid (MPA) azathioprine (AZA) have been identified factors for hypo-responsiveness. Methods We hypothesized that non-responders to least previous doses, pausing MPA AZA 1 week before an additional vaccination would improve rates. conducted open-label, non-randomized controlled pilot study including 40 KTR no detectable four doses. Primary endpoint was seroconversion following SARS-CoV-2 vaccination. paused 18 patients until dose while continued 22 patients. Results There difference rate between MPA/AZA pause group control (29 vs. 32%, p &gt; 0.99). Absolute antibody levels were also not statistically significantly different groups ( = 0.716).Renal function remained stable there detection new onset donor-specific antibodies increase donor-derived cell-free DNA serving a marker allograft damage throughout period. Conclusion Pausing 2 weeks peri-vaccination did kidney transplant. one without immune vaccinations developed supporting non-responders.

Язык: Английский

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Serological Response to Three, Four and Five Doses of SARS-CoV-2 Vaccine in Kidney Transplant Recipients

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Март 27, 2022

Abstract Mortality from COVID-19 among kidney transplant recipients (KTR) is high, and their response to three vaccinations against SARS-CoV-2 strongly impaired. We retrospectively analyzed serological of up five doses vaccine in KTR December 27, 2020, until 31, 2021. Particularly, the influence different dose adjustment regimens for mycophenolic acid (MPA) on fourth vaccination was analyzed. In total, 4.277 1.478 patients were Serological 19.5% after 1.203 basic immunizations, increased 29.4%, 55.6%, 57.5% 603 third, 250 40 fifth vaccinations, resulting a cumulative rate 88.7%. with calcineurin inhibitor MPA maintenance immunosuppression, pausing adding 5 mg prednisolone equivalent before 75% comparison no (52%) or reduction (46%). Belatacept-treated had 8.7% (4/46) 12.5% (3/25) four vaccinations. Except belatacept-treated patients, repeated times effectively induces recipients. It can be enhanced by at time vaccination.

Язык: Английский

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A Randomized Trial of Valganciclovir Prophylaxis Versus Preemptive Therapy in Kidney Transplant Recipients

Journal of the American Society of Nephrology, Год журнала: 2023, Номер 34(5), С. 920 - 934

Опубликована: Фев. 2, 2023

Significance Statement Although cytomegalovirus (CMV) infection is an important factor in the pathogenesis of kidney allograft rejection, previous studies have not determined optimal CMV prevention strategy to avoid indirect effects virus. In this randomized trial involving 140 transplant recipients, incidence acute rejection at 12 months was lower with valganciclovir prophylaxis (for least 3 months) compared preemptive therapy initiated after detection DNA whole blood. However, associated a risk subclinical months. both regimens were effective preventing disease, DNAemia (including episodes higher viral loads) significantly therapy. Further research long-term follow-up warranted better compare two approaches. Background The regimen for primarily reducing effects, has been defined. Methods This open-label, single-center, clinical versus included recipients recruited between June 2013 and May 2018. After excluding CMV-seronegative transplants from seronegative donors, we participants 1:1 receive (900 mg, daily or 6 who received CMV-seropositive donor) (valganciclovir, 900 twice daily) that blood (≥1000 IU/ml) stopped consecutive negative tests (preemptive patients weekly PCR 4 months). primary outcome biopsy-confirmed Key secondary outcomes disease DNAemia, neutropenia. Results than (13%, 9/70 23%, 16/70), but difference statistically significant. Subclinical group (13% 29%, P = 0.027). Both prevented (in 4% groups). Compared prophylaxis, resulted rates (44% 75%, < 0.001) proportion experiencing load (≥2000 IU/ml), exposure Conclusion Among use did result Clinical Trial Registry Name Registration Number Optimizing Valganciclovir Efficacy Renal Transplantation (OVERT Study), ACTRN12613000554763.

Язык: Английский

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