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

• Published in: Vaccines (Basel) Vol. 12; no. 5; p. 518
• Main Authors: Wagner, Angelika, Garner-Spitzer, Erika, Auer, Claudia, Gattinger, Pia, Zwazl, Ines, Platzer, René, Orola-Taus, Maria, Pichler, Peter, Amman, Fabian, Bergthaler, Andreas, Huppa, Johannes B., Stockinger, Hannes, Zielinski, Christoph C., Valenta, Rudolf, Kundi, Michael, Wiedermann, Ursula
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.05.2024
• Subjects: Antibodies; Antigens; Austria; B cells; Blood; breakthrough infection; Carfilzomib; CD38 antigen; COVID-19; COVID-19 vaccines; Cross-protection; Cytokines; Development and progression; Drug dosages; Ethylenediaminetetraacetic acid; Health aspects; immune cell depletion; immune response; Immunological memory; Immunology; immunosuppression; Immunotherapy; Infection; Infections; Inflammatory bowel disease; Lymphocytes; Memory (Computers); Memory cells; Monoclonal antibodies; Monoclonal gammopathy; Morbidity; Mortality; mRNA; Multiple myeloma; Peptides; Proteins; RNA; SARS-CoV-2 vaccination; Severe acute respiratory syndrome coronavirus 2; Software; Stem cell transplantation; Stem cells; Transplantation; Vaccination; Vaccines; Viral diseases; Austria; United States > US; Germany; SARS-CoV-2 vaccination; multiple myeloma; B memory cells; immune response; breakthrough infection; immune cell depletion; immunosuppression
• DOI: 10.3390/vaccines12050518
• ISSN: 2076-393X

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.