BA.1/BA.5 immunogenicity, reactogenicity, and disease activity after covid-19 vaccination in patients with anca-associated vasculitis: a prospective observational cohort study

Emerging omicron subtypes with immune escape lead to inadequate vaccine response with breakthrough infections in immunocompromised individuals such as Anti-neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis (AAV) patients. As AAV is considered an orphan disease, there are still limited dat...

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Main Authors: Speer, Claudius (Author) , Töllner, Maximilian (Author) , Benning, Louise (Author) , Bartenschlager, Marie (Author) , Kim, Heeyoung (Author) , Nußhag, Christian (Author) , Kälble, Florian (Author) , Reineke, Marvin (Author) , Reichel, Paula (Author) , Schnitzler, Paul (Author) , Zeier, Martin (Author) , Morath, Christian (Author) , Schmitt, Wilhelm (Author) , Bergner, Raoul (Author) , Bartenschlager, Ralf (Author) , Lorenz, Hanns-Martin (Author) , Schaier, Matthias (Author)
Format: Article (Journal)
Language:English
Published: 21 August 2023
In: Viruses
Year: 2023, Volume: 15, Issue: 8
ISSN:1999-4915
DOI:10.3390/v15081778
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/v15081778
Verlag, kostenfrei, Volltext: https://www.mdpi.com/1999-4915/15/8/1778
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Author Notes:Claudius Speer, Maximilian Töllner, Louise Benning, Marie Bartenschlager, Heeyoung Kim, Christian Nusshag, Florian Kälble, Marvin Reineke, Paula Reichel, Paul Schnitzler, Martin Zeier, Christian Morath, Wilhelm Schmitt, Raoul Bergner, Ralf Bartenschlager, Hanns-Martin Lorenz, Matthias Schaier

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520 |a Emerging omicron subtypes with immune escape lead to inadequate vaccine response with breakthrough infections in immunocompromised individuals such as Anti-neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis (AAV) patients. As AAV is considered an orphan disease, there are still limited data on SARS-CoV-2 vaccination and prospective studies that have focused exclusively on AAV patients are lacking. In addition, there are safety concerns regarding the use of highly immunogenic mRNA vaccines in autoimmune diseases, and further studies investigating reactogenicity are urgently needed. In this prospective observational cohort study, we performed a detailed characterization of neutralizing antibody responses against omicron subtypes and provided a longitudinal assessment of vaccine reactogenicity and AAV disease activity. Different vaccine doses were generally well tolerated and no AAV relapses occurred during follow-up. AAV patients had significantly lower anti-S1 IgG and surrogate-neutralizing antibodies after first, second, and third vaccine doses as compared to healthy controls, respectively. Live-virus neutralization assays against omicron subtypes BA.1 and BA.5 revealed that previous SARS-CoV-2 vaccines result in an inadequate neutralizing immune response in immunocompromised AAV patients. These data demonstrate that new vaccination strategies including adapted mRNA vaccines against epitopes of emerging variants are needed to help protect highly vulnerable individuals such as AAV patients. 
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