EBioMedicine (Dec 2023)
Cellular mechanisms associated with sub-optimal immune responses to SARS-CoV-2 bivalent booster vaccination in patients with Multiple MyelomaResearch in context
- Adolfo Aleman,
- Morgan van Kesteren,
- Ariel Kogan Zajdman,
- Komal Srivastava,
- Christian Cognigni,
- Jacob Mischka,
- Lucia Y. Chen,
- Bhaskar Upadhyaya,
- Kseniya Serebryakova,
- Jessica R. Nardulli,
- Neko Lyttle,
- Katerina Kappes,
- Hayley Jackson,
- Charles R. Gleason,
- Annika Oostenink,
- Gianna Y. Cai,
- Oliver Van Oekelen,
- Harm van Bakel,
- Emilia Mia Sordillo,
- Carlos Cordon-Cardo,
- Miriam Merad,
- Sundar Jagannath,
- Ania Wajnberg,
- Viviana Simon,
- Samir Parekh,
- Hala Alshammary,
- Dalles Andre,
- Radhika Banu,
- Katherine Beach,
- María Carolina Bermúdez-González,
- Ajai Chari,
- Yuexing Chen,
- Hearn Cho,
- Adolfo Firpo,
- Ana Silvia Gonzalez-Reiche,
- Eun Hye Kim,
- Giulio Kleiner,
- Florian Krammer,
- Jacob Mauldin,
- Rao Mendu,
- Brian Monahan,
- Shambavi Richard,
- Joshua Richter,
- Cesar Rodriguez,
- Adrianna Rossi,
- Ashley Salimbangon,
- Laryssa Sanchez,
- Daniel Verina
Affiliations
- Adolfo Aleman
- Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Morgan van Kesteren
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Ariel Kogan Zajdman
- Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Komal Srivastava
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Christian Cognigni
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Jacob Mischka
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Lucia Y. Chen
- Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Bhaskar Upadhyaya
- Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Kseniya Serebryakova
- Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Jessica R. Nardulli
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Neko Lyttle
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Katerina Kappes
- Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Hayley Jackson
- Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Charles R. Gleason
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Annika Oostenink
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Gianna Y. Cai
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Oliver Van Oekelen
- Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Harm van Bakel
- Department of Pathology, Molecular and Cell-based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, NY, USA
- Emilia Mia Sordillo
- Department of Pathology, Molecular and Cell-based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Carlos Cordon-Cardo
- Department of Pathology, Molecular and Cell-based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, NY, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Miriam Merad
- Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Sundar Jagannath
- Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Ania Wajnberg
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, NY, USA
- Viviana Simon
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Molecular and Cell-based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Division of Infectious Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogen Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Corresponding author. Mount Sinai Hospital, Icahn School of Medicine, One Gustave L. Levy Place, Box 1185, New York, NY 10029, USA.
- Samir Parekh
- Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Corresponding author. Mount Sinai Hospital, Icahn School of Medicine, One Gustave L. Levy Place, Box 1185, New York, NY 10029, USA.
- Hala Alshammary
- Dalles Andre
- Radhika Banu
- Katherine Beach
- María Carolina Bermúdez-González
- Ajai Chari
- Yuexing Chen
- Hearn Cho
- Adolfo Firpo
- Ana Silvia Gonzalez-Reiche
- Eun Hye Kim
- Giulio Kleiner
- Florian Krammer
- Jacob Mauldin
- Rao Mendu
- Brian Monahan
- Shambavi Richard
- Joshua Richter
- Cesar Rodriguez
- Adrianna Rossi
- Ashley Salimbangon
- Laryssa Sanchez
- Daniel Verina
- Journal volume & issue
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Vol. 98
p. 104886
Abstract
Summary: Background: The real-world impact of bivalent vaccines for wild type (WA.1) and Omicron variant (BA.5) is largely unknown in immunocompromised patients with Multiple Myeloma (MM). We characterize the humoral and cellular immune responses in patients with MM before and after receiving the bivalent booster, including neutralizing assays to identify patterns associated with continuing vulnerability to current variants (XBB1.16, EG5) in the current post-pandemic era. Methods: We studied the humoral and cellular immune responses before and after bivalent booster immunization in 48 MM patients. Spike binding IgG antibody levels were measured by SARS-CoV-2 spike binding ELISA and neutralization capacity was assessed by a SARS-CoV-2 multi-cycle microneutralization assays to assess inhibition of live virus. We measured spike specific T-cell function using the QuantiFERON SARS-CoV-2 (Qiagen) assay as well as flow-cytometry based T-cell. In a subset of 38 patients, high-dimensional flow cytometry was performed to identify immune cell subsets associated with lack of humoral antibodies. Findings: We find that bivalent vaccination provides significant boost in protection to the omicron variant in our MM patients, in a treatment specific manner. MM patients remain vulnerable to newer variants with mutations in the spike portion. Anti-CD38 and anti-BCMA therapies affect the immune machinery needed to produce antibodies. Interpretation: Our study highlights varying immune responses observed in MM patients after receiving bivalent COVID-19 vaccination. Specifically, a subgroup of MM patients undergoing anti-CD38 and anti-BCMA therapy experience impairment in immune cells such DCs, B cells, NK cells and TFH cells, leading to an inability to generate adequate humoral and cellular responses to vaccination. Funding: National Cancer Institute (National Institutes of Health), National Institute of Allergy and Infectious Diseases (National Institutes of Health), NCI Serological Sciences Network for COVID-19 (SeroNet) and The Icahn School of Medicine at Mount Sinai.
