Neutralizing antibody response against the B.1.617.2 (delta) and the B.1.1.529 (omicron) variants after a third mRNA SARS-CoV-2 vaccine dose in kidney transplant recipients

Benning, Louise; Morath, Christian; Bartenschlager, Marie; Kim, Heeyoung; Reineke, Marvin; Beimler, Jörg; Buylaert, Mirabel; Nußhag, Christian; Kälble, Florian; Reichel, Paula; Töllner, Maximilian; Schaier, Matthias; Klein, Katrin; Beneš, Vladimı́r; Rausch, Tobias; Rieger, Susanne; Stich, Maximilian; Tönshoff, Burkhard; Weidner, Niklas; Schnitzler, Paul; Zeier, Martin; Süsal, Caner; Tran, Thuong Hien; Bartenschlager, Ralf; Speer, Claudius

doi:10.1111/ajt.17054

Cited by 44 publications

(63 citation statements)

References 83 publications

(224 reference statements)

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“…It is not surprising, but alarming, that only 4 at of a total of 47 COVID-naïve SOTRs cohort produced levels of omicron-neutralizing antibodies comparable to those from HCs. Our finding appears to be in an agreement with a recent study by Benning et al 17 , who demonstrated that vaccine-induced cross-neutralization against omicron was detectable in 43% (15/35) anti-S1 IgG-seropositive kidney transplant patients. Omicron variants have been shown to be well-equipped to escape from neutralization by many therapeutic monoclonal antibodies, yet retain a high affinity for the ACE2 receptor 18,19 .…”

Section: Discussionsupporting

confidence: 94%

Previous SARS-CoV-2 infection or a third dose of vaccine elicited cross-variant neutralizing antibodies in vaccinated solid organ transplant recipients

Chang

Vlad

Vasilescu

et al. 2022

Preprint

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The SARS-CoV-2 pandemic poses a great threat to global health, particularly in solid organ transplant recipients (SOTRs). Although a 3-dose mRNA vaccination protocol has been implemented for the majority of SOTRs, its effectiveness was still largely unknown. We analyzed 113 vaccinated SOTRs, and 30 healthy controls (HCs), some of whom had recovered from COVID, for their immune responses against the original vaccine strain and variants of concern (VOC), including the highly mutated-omicron variant. Here, we report that 3 doses of the mRNA vaccine had only a modest effect in eliciting anti-viral responses against all viral strains in the fully vaccinated SOTRs who did not contract the virus. Only 34.0% (16/47) of this group of patients demonstrated both detectable anti-RBD IgG and neutralization activities against alpha, beta, and delta variants, and only 8.5% (4/47) of them showed additional omicron-neutralizing capacities. In contrast, 79.5% (35/44) of the vaccinated recovered-SOTRs demonstrated both higher anti-RBD IgG levels and neutralizing activities against all VOC, including omicron. These findings illustrate a significant impact of previous infection on the development of anti-COVID immune responses in vaccinated SOTRs and highlight the need for alternative strategies to protect a subset of a lesser-vaccine responsive population.

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Section: Discussionsupporting

confidence: 94%

Previous SARS-CoV-2 infection or a third dose of vaccine elicited cross-variant neutralizing antibodies in vaccinated solid organ transplant recipients

Chang

Vlad

Vasilescu

et al. 2022

Preprint

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“…Higher humoral immune responses as determined by antispike-antibody determinations and sVNT tests have been reported for boostered vaccinees by several studies (15)(16)(17)(18)(19)(20). Additionally, a higher immune response in boostered vaccinees compared to individuals, who only have been vaccinated twice, against the Omicron variant, which nevertheless is weaker than against the wild type virus, has been reported as well (21,22).…”

Section: Discussionmentioning

confidence: 75%

Individuals With Weaker Antibody Responses After Booster Immunization Are Prone to Omicron Breakthrough Infections

et al. 2022

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BackgroundDespite the high level of protection against severe COVID-19 provided by the currently available vaccines some breakthrough infections occur. Until now, there is no information whether a potential risk of a breakthrough infection can be inferred from the level of antibodies after booster vaccination.MethodsLevels of binding antibodies and neutralization capacity after the first, one and six month after the second, and one month after the third (booster) vaccination against COVID-19 were measured in serum samples from 1391 healthcare workers at the University Hospital Essen. Demographics, vaccination scheme, pre-infection antibody titers and neutralization capacity were compared between individuals with and without breakthrough infections.ResultsThe risk of developing an Omicron breakthrough infection was independent of vaccination scheme, sex, body mass index, smoking status or pre-existing conditions. In participants with low pre-infection anti-spike antibodies (≤ 2641.0 BAU/ml) and weaker neutralization capacity (≤ 65.9%) against Omicron one month after the booster vaccination the risk for developing an Omicron infection was 10-fold increased (P = 0.001; 95% confidence interval, 2.36 - 47.55).ConclusionRoutine testing of anti-SARS-CoV-2 IgG antibodies and surrogate virus neutralization can quantify vaccine-induced humoral immune response and may help to identify subjects who are at risk for a breakthrough infection. The establishment of thresholds for SARS-CoV-2 IgG antibody levels identifying “non”-, “low” and “high”-responders may be used as an indication for re-vaccination.

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“…Importantly, receipt of a third vaccine yielded a significant increase in the proportion of patients with neutralizing capacity against the WT, Beta, Delta and Omicron variants after one month; however, this response was inferior to that observed in healthy controls. Data on the development of an Omicron-specific neutralizing response among KTRs are limited, with rates of 12% (37) and 43% (38) reported at one month. We detected neutralizing antibody to Omicron in over 45% of our cohort at one month, with sustained response in 38.5% at three months following the third mRNA vaccine dose.…”

Section: Discussionmentioning

confidence: 99%

Humoral Responses in the Omicron Era following Three-Dose SARS-CoV-2 Vaccine Series in Kidney Transplant Recipients

McEvoy

Abe

et al. 2022

Preprint

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Background: Kidney transplant recipients (KTR) have a diminished response to SARS-CoV-2 vaccination in comparison to immunocompetent individuals. Deeper understanding of the antibody response in KTRs following third-dose vaccination would enable identification of those who remain unprotected against Omicron and require additional treatment strategies. Methods: We profiled antibody responses in KTRs pre- and at one and three months post-third-dose SARS-CoV2 mRNA-based vaccine. Anti-spike and anti-RBD IgG levels were determined by ELISA. Neutralization against wild-type, Beta, Delta and Omicron (BA.1) variants was determined using a SARS-CoV-2 spike pseudotyped lentivirus assay. Results: 44 KTRs were analysed at 1 and 3 months (n=26) post-third-dose. At one month, the proportion of participants with a robust antibody response had increased significantly from baseline, but Omicron-specific neutralizing antibodies were detected in just 45% of KTRs. Median binding antibody levels declined at 3 months, but the proportion of KTRs with a robust antibody response was unchanged. 38.5% KTRs maintained Omicron-specific neutralization at 3 months. No clinical variables were significantly associated with detectable Omicron neutralizing antibodies, but anti-RBD titres appeared to identify those with Omicron-specific neutralizing capacity. Conclusion: Over 50% of KTRs lack an Omicron-specific neutralization response 1 month following a third mRNA-vaccine dose. Among responders, binding and neutralizing antibody responses were well preserved at 3 months. Anti-RBD antibody titres may be a useful identifier of patients with detectable Omicron neutralizing antibody response. Trial registration: Clinical Trials Ontario: ID 3604

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Neutralizing antibody response against the B.1.617.2 (delta) and the B.1.1.529 (omicron) variants after a third mRNA SARS-CoV-2 vaccine dose in kidney transplant recipients

Cited by 44 publications

References 83 publications

Previous SARS-CoV-2 infection or a third dose of vaccine elicited cross-variant neutralizing antibodies in vaccinated solid organ transplant recipients

Previous SARS-CoV-2 infection or a third dose of vaccine elicited cross-variant neutralizing antibodies in vaccinated solid organ transplant recipients

Individuals With Weaker Antibody Responses After Booster Immunization Are Prone to Omicron Breakthrough Infections

Humoral Responses in the Omicron Era following Three-Dose SARS-CoV-2 Vaccine Series in Kidney Transplant Recipients

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