Antibody Binding and Angiotensin-Converting Enzyme 2 Binding Inhibition Is Significantly Reduced for Both the BA.1 and BA.2 Omicron Variants

Junker, Daniel; Becker, Matthias; Wagner, Teresa R.; Kaiser, Philipp; Maier, Sandra; Grimm, Tanja M; Griesbaum, Johanna; Marsall, Patrick; Gruber, Jens; Traenkle, Bjoern; Heinzel, Constanze; Pinilla, Yudi T.; Held, Jana; Fendel, Rolf; Kreidenweiss, Andrea; Nelde, Annika; Maringer, Yacine; Schroeder, Sarah; Walz, Juliane S.; Althaus, Karina; Uzun, Günalp; Mikus, Marco; Bakchoul, Tamam; Schenke‐Layland, Katja; Bunk, Stefanie; Haeberle, Helene A.; Göpel, Siri; Bitzer, Michael; Renk, Hanna; Remppis, Jonathan; Engel, Corinna; Franz, Axel; Harries, Manuela; Kessel, Barbora; Lange, Berit; Strengert, Monika; Krause, Gérard; Zeck, Anne; Rothbauer, Ulrich; Dulovic, Alex; Schneiderhan‐Marra, Nicole

doi:10.1093/cid/ciac498

Cited by 14 publications

(12 citation statements)

References 27 publications

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“…To characterise the vaccination response after the third BN162b2 vaccination in 50 patients on maintenance haemodialysis, we had followed immunoglobulin levels longitudinally after the second dose of BNT162b2 using MULTICOV-AB, a multiplex immunoassay containing antigens from the Spike protein of SARS-CoV-2 and selected variants of concern ( 9 ). As a novel control group, 33 samples from healthcare workers with triple BNT162b2 vaccination were used for comparison.…”

Section: Resultsmentioning

confidence: 99%

“…IgG binding and levels were analysed using MULTICOV-AB, a multiplex coronavirus immunoassay which contains the trimeric Spike B.1, its subdomains (S1, S2, RBD), nucleocapsid B.1 and RBDs of Delta and Omicron BA.1 antigens as previously described ( 9 , 19 ). Briefly, antigens were immobilised on spectrally distinct populations of MagPlex beads (Cat #MC10XXX-01, Luminex Corporation) either by EDC/s-NHS coupling ( 21 ) or by Anteo coupling (Cat #A-LMPAKMM-10, Anteo Tech Reagents) following the manufacturer’s instruction ( 19 ).…”

Section: Methodsmentioning

confidence: 99%

“…Starting in mid-2021 and more widely since the beginning of 2022, several countries recommended a fourth dose of SARS-CoV-2 mRNA vaccines for immunosuppressed populations at-risk for severe COVID-19 disease and older individuals to maintain levels of immune protection ( 5 – 8 ). This was driven by weaker peak vaccine responses and waning immunity in those individuals as well as continued evolution of SARS-CoV-2 variants with increasing levels of immune evasion potential as demonstrated for Omicron VoC subspecies BA.1, BA.4, BA.5, and BA.2.12.1 ( 9 – 12 ).…”

Section: Introductionmentioning

confidence: 99%

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Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients

Becker

Cossmann²,

Lürken³

et al. 2022

Front. Immunol.

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Haemodialysis patients respond poorly to vaccination and continue to be at-risk for severe COVID-19. Therefore, dialysis patients were among the first for which a fourth COVID-19 vaccination was recommended. However, targeted information on how to best maintain immune protection after SARS-CoV-2 vaccinations in at-risk groups for severe COVID-19 remains limited. We provide, to the best of our knowledge, for the first time longitudinal vaccination response data in dialysis patients and controls after a triple BNT162b2 vaccination and in the latter after a subsequent fourth full-dose of mRNA-1273. We analysed systemic and mucosal humoral IgG responses against the receptor-binding domain (RBD) and ACE2-binding inhibition towards variants of concern including Omicron and Delta with multiplex-based immunoassays. In addition, we assessed Spike S1-specific T-cell responses by interferon γ release assay. After triple BNT162b2 vaccination, anti-RBD B.1 IgG and ACE2 binding inhibition reached peak levels in dialysis patients, but remained inferior compared to controls. Whilst we detected B.1-specific ACE2 binding inhibition in 84% of dialysis patients after three BNT162b2 doses, binding inhibition towards the Omicron variant was only detectable in 38% of samples and declining to 16% before the fourth vaccination. By using mRNA-1273 as fourth dose, humoral immunity against all SARS-CoV-2 variants tested was strongly augmented with 80% of dialysis patients having Omicron-specific ACE2 binding inhibition. Modest declines in T-cell responses in dialysis patients and controls after the second vaccination were restored by the third BNT162b2 dose and significantly increased by the fourth vaccination. Our data support current advice for a four-dose COVID-19 immunisation scheme for at-risk individuals such as haemodialysis patients. We conclude that administration of a fourth full-dose of mRNA-1273 as part of a mixed mRNA vaccination scheme to boost immunity and to prevent severe COVID-19 could also be beneficial in other immune impaired individuals. Additionally, strategic application of such mixed vaccine regimens may be an immediate response against SARS-CoV-2 variants with increased immune evasion potential.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients

Becker

Cossmann²,

Lürken³

et al. 2022

Front. Immunol.

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“…Due to declining antibody titers, booster vaccination was recommended to prolong protection against COVID-19. Furthermore, it has been shown that the antibodies that are developed after vaccines using the spike protein of a wild-type virus have a limited neutralization ability against new variants of the virus [ 33 ]. A third vaccination improves the antibody binding to the omicron variant [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Vaccine Side Effects in Health Care Workers after Vaccination against SARS-CoV-2: Data from TüSeRe:exact Study

Bareiß¹,

Uzun²,

Mikus³

et al. 2022

Viruses

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As the Corona Disease 2019 (COVID-19) caused by SARS-CoV-2 persists, vaccination is one of the key measures to contain the spread. Side effects (SE) from vaccination are one of the reasons for reluctance to vaccinate. We systematically investigated self-reported SE after the first, second, and booster vaccinations. The data were collected during the TüSeRe: exact study (Tübinger Monitoring Studie zur exakten Analyse der Immunantwort nach Vakzinierung). Employees of health and research institutions were invited to participate. Study participants were asked to fill out an online questionnaire and report their SE after each dose of SARS-CoV-2 vaccination. A total of 1046 participants (mean age: 44 ± 12.9 years; female, n = 815 (78%); male, n = 231 (22%)) were included in the analysis. Local and systemic SE were more frequent after receiving the vector-based vaccine ChAdOx1 nCoV-19 in the first vaccination. However, local and systemic SE were more common after receiving mRNA vaccines (BNT162b2, mRNA-1273) in the second vaccination. Compared to the BNT162b2 vaccine, more SE have been observed after receiving the mRNA-1273 vaccine in the booster vaccination. In multivariate analysis, local and systemic side effects were associated with vaccine type, age and gender. Local and systemic SE are common after SARS-CoV-2 vaccines. The frequency of self-reported local and systemic SE differ significantly between mRNA and vector-based vaccines.

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“…Plates were read on a FLEXMAP3D instrument (Luminex, United States) using the following settings: 80 µL (no timeout), 50 events, Gate 7500-15000, Standard PMT. Each plate included 3 wells with 150 ng/mL ACE2, 2 blank wells and 3 wells with a quality control (QC) sample as controls [25]. For each variant, ACE2 inhibition was calculated as a percentage, with 100% indicating maximum ACE2 inhibition and 0% indicating no ACE2 inhibition.…”

Section: Ace2 Binding Inhibition Assay Methodologymentioning

confidence: 99%

Assessment of Immunogenicity and Efficacy of CV0501 mRNA-based Omicron COVID-19 Vaccination in Small Animal Models

Roth

Gergen

Kovacikova

et al. 2023

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron and its subvariants (BA.2, BA.4, BA.5) represent the most commonly circulating variants of concern (VOC) in the coronavirus disease 2019 (COVID-19) pandemic in 2022. Despite high vaccination rates with approved SARS-CoV-2 vaccines encoding the ancestral spike (S) protein, these Omicron subvariants have collectively resulted in increased viral transmission and disease incidence. This necessitates the development and characterization of vaccines incorporating later emerging S proteins to enhance protection against VOC. In this context, bivalent vaccine formulations may induce broad protection against VOC and potential future SARS CoV 2 variants. Here, we report preclinical data for a lipid nanoparticle (LNP) formulated RNActive N1-methylpseudouridine (N1mΨ) modified mRNA vaccine (CV0501) based on our second-generation SARS-CoV-2 vaccine CV2CoV, encoding the S protein of Omicron BA.1. The immunogenicity of CV0501, alone or in combination with a corresponding vaccine encoding the ancestral S protein (ancestral N1mΨ), was first measured in dose-response and booster immunization studies performed in Wistar rats. Both monovalent CV0501 and bivalent CV0501/ancestral N1mΨ immunization induced robust neutralizing antibody titers against the BA.1, BA.2 and BA.5 Omicron subvariants, in addition to other SARS-CoV-2 variants in a booster immunization study. The protective efficacy of monovalent CV0501 against live SARS-CoV-2 BA.2 infection was then assessed in hamsters. Monovalent CV0501 significantly reduced SARS CoV 2 BA.2 viral loads in the airways, demonstrating protection induced by CV0501 vaccination. CV0501 has now advanced into human Phase 1 clinical trials (ClinicalTrials.gov Identifier:NCT05477186).

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Antibody Binding and Angiotensin-Converting Enzyme 2 Binding Inhibition Is Significantly Reduced for Both the BA.1 and BA.2 Omicron Variants

Cited by 14 publications

References 27 publications

Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients

Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients

Vaccine Side Effects in Health Care Workers after Vaccination against SARS-CoV-2: Data from TüSeRe:exact Study

Assessment of Immunogenicity and Efficacy of CV0501 mRNA-based Omicron COVID-19 Vaccination in Small Animal Models

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