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

Schrezenmeier, Eva; Rincón‐Arévalo, Héctor; Jens, Annika; Stefanski, Ana‐Luisa; Hammett, Charlotte; Osmanodja, Bilgin; Koch, Nadine; Zukunft, Bianca; Beck, Julia; Oellerich, Michael; Proß, Vanessa; Stahl, Carolin; Choi, Mira; Bachmann, Friederike; Liefeldt, Lutz; Glander, Petra; Schütz, Ekkehard; Bornemann-Kolatzki, Kirsten; Cuesta, Covadonga López del Moral; Schrezenmeier, Hubert; Ludwig, Carolin; Jahrsdörfer, Bernd; Eckardt, Kai‐Uwe; Lachmann, Nils; Kotsch, Katja; Dörner, Thomas; Halleck, Fabian; Sattler, Arne; Budde, Klemens

doi:10.1172/jci.insight.157836

Cited by 69 publications

(76 citation statements)

References 46 publications

(56 reference statements)

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“…Schrezenmeier et al reported that withholding MPA for 5 weeks around a 4th vaccination in KTR resulted in a much higher seroconversion rate of 76% after 4 weeks, and even 84% in patients on a CNI-based immunosuppressive regimen (19). There are several differences in the study population and intervention: MPA pause in our study was much shorter (2 vs. 5 weeks).…”

Section: Discussionmentioning

confidence: 54%

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

Regele

Heinzel

et al. 2022

Front. Med.

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

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Section: Discussionmentioning

confidence: 54%

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

Regele

Heinzel

et al. 2022

Front. Med.

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“…As described for a patient co-infected with HIV and SARS-CoV-2 ( 1 ), this may potentially allow for the temporary emergence and accumulation of additional viral mutations within the infected individual. The participants included in our study had no history of diseases or medications affecting systemic immunity, which may also have a negative impact on vaccination responses ( 29 – 34 ). However, it may be hypothesized that individuals with only mildly compromised immune status can still develop a delayed memory immune response against individually occurring viral mutations, thereby containing and eradicating the corresponding individual viral variants, before further spreading of the virus to persons outside the LTCFs can occur.…”

Section: Discussionmentioning

confidence: 99%

BNT162b2 Booster Vaccination Elicits Cross-Reactive Immunity Against SARS-CoV-2 Variants B.1.1.529 and B.1.617.2 in Convalescents of All Ages

et al. 2022

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In this prospective observational cohort study we analyzed cellular and serological immune response parameters against SARS-CoV-2 and current variants of concern (VOC) in 147 COVID-19-convalescent and 39 COVID-19-naïve individuals before and after BNT162b2 booster vaccination. No significant differences regarding immunological response parameters were observed between younger and older individuals. Booster vaccination induced full recovery of both cellular and serological response parameters including IFN-γ secretion and anti-spike antibody titers with strong neutralization capacities against wild type SARS-COV-2 and Delta. Surprisingly, even serological neutralization capacity against Omicron was detectable one month after second vaccination and four months before it had been first observed in South Africa. As a result, more than 90% of convalescent individuals exhibited detectable and 75% strong Omicron neutralization capacity after booster vaccination, compared with 72% and 46% of COVID-19-naïve individuals. Our results support the notion that broad and cross-reactive immune memory against SARS-CoV-2 including currently known VOCs can be established by booster vaccination with spike-based mRNA vaccines like BNT162b2, particularly in COVID-19-convalescent individuals of all ages. Nevertheless, especially in COVID-19-naïve individuals future variants escaping the memory immune response may require vaccine approaches such as inactivated whole virus vaccines, which include all antigenic components of the virus.

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“…To our knowledge, this is the first report to investigate the effects of mycophenolate mofetil dose on anti-SARS-CoV-2 IgG antibody response in patients with systemic sclerosis, with patients on high-dose mycophenolate mofetil the least likely to have detectable antibodies. Although a temporary peri-vaccination hold of mycophenolate mofetil augments humoral response in transplant recipients and in patients with rheumatic diseases, 8 , 9 this might not be appropriate for all patients; temporary use of low-dose mycophenolate mofetil might represent an alternative strategy to enhance SARS-CoV-2 vaccine response. Our findings highlight the need for ongoing studies to evaluate additional strategies, such as peri-vaccination modulation of immunosuppression, additional vaccine doses, and consideration of pre-exposure prophylaxis to protect this susceptible patient population.…”

mentioning

confidence: 99%

Effect of mycophenolate mofetil dose on antibody response following initial SARS-CoV-2 vaccination in patients with systemic sclerosis

Wallwork

Connolly

Shneyderman

et al. 2022

The Lancet Rheumatology

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

Cited by 69 publications

References 46 publications

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

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

BNT162b2 Booster Vaccination Elicits Cross-Reactive Immunity Against SARS-CoV-2 Variants B.1.1.529 and B.1.617.2 in Convalescents of All Ages

Effect of mycophenolate mofetil dose on antibody response following initial SARS-CoV-2 vaccination in patients with systemic sclerosis

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