Breakthrough Infections in SARS-CoV-2-Vaccinated Multiple Myeloma Patients Improve Cross-Protection against Omicron Variants

Angelika Wagner, Erika Garner-Spitzer, Claudia Auer, Pia Gattinger, Ines Zwazl, René Platzer, Maria Orola-Taus, Peter Pichler, Fabian Amman, Andreas Bergthaler, Johannes B Huppa, Hannes Stockinger, Christoph C Zielinski, Rudolf Valenta, Michael Kundi, Ursula Wiedermann

Research output: Journal article (peer-reviewed)Journal article

Abstract

Patients with multiple myeloma (MM) are a heterogenous, immunocompromised group with increased risk for COVID-19 morbidity and mortality but impaired responses to primary mRNA SARS-CoV-2 vaccination. The effects of booster vaccinations and breakthrough infections (BTIs) on antibody (Ab) levels and cross-protection to variants of concern (VOCs) are, however, not sufficiently evaluated. Therefore, we analysed humoral and cellular vaccine responses in MM patients stratified according to disease stage/treatment into group (1) monoclonal gammopathy of undetermined significance, (2) after stem cell transplant (SCT) without immunotherapy (IT), (3) after SCT with IT, and (4) progressed MM, and in healthy subjects (prospective cohort study). In contrast to SARS-CoV-2 hu-1-specific Ab levels, Omicron-specific Abs and their cross-neutralisation capacity remained low even after three booster doses in a majority of MM patients. In particular, progressed MM patients receiving anti-CD38 mAb and those after SCT with IT were Ab low responders and showed delayed formation of spike-specific B memory cells. However, MM patients with hybrid immunity (i.e., vaccination and breakthrough infection) had improved cross-neutralisation capacity against VOCs, yet in the absence of severe COVID-19 disease. Our results indicate that MM patients require frequent variant-adapted booster vaccinations and/or changes to other vaccine formulations/platforms, which might have similar immunological effects as BTIs.

Original languageEnglish
Article number518
JournalVaccines
Volume12
Issue number5
DOIs
Publication statusPublished - 09 May 2024

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