Low Spike Antibody Levels and Impaired BA.4/5 Neutralization in Patients with Multiple Myeloma or Waldenstrom’s Macroglobulinemia after BNT162b2 Booster Vaccination
Patients with symptomatic monoclonal gammopathies have impaired humoral responses to COVID-19 vaccination. Their ability to recognize SARS-CoV-2 Omicron variants is of concern. We compared the response to BNT162b2 mRNA vaccinations of patients with multiple myeloma (MM, n = 60) or Waldenstrom’s macr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/23/5816 |
| _version_ | 1797463533449904128 |
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| author | Margherita Rosati Evangelos Terpos Jenifer Bear Robert Burns Santhi Devasundaram Ioannis Ntanasis-Stathopoulos Maria Gavriatopoulou Efstathios Kastritis Meletios-Athanasios Dimopoulos George N. Pavlakis Barbara K. Felber |
| author_facet | Margherita Rosati Evangelos Terpos Jenifer Bear Robert Burns Santhi Devasundaram Ioannis Ntanasis-Stathopoulos Maria Gavriatopoulou Efstathios Kastritis Meletios-Athanasios Dimopoulos George N. Pavlakis Barbara K. Felber |
| author_sort | Margherita Rosati |
| collection | DOAJ |
| description | Patients with symptomatic monoclonal gammopathies have impaired humoral responses to COVID-19 vaccination. Their ability to recognize SARS-CoV-2 Omicron variants is of concern. We compared the response to BNT162b2 mRNA vaccinations of patients with multiple myeloma (MM, n = 60) or Waldenstrom’s macroglobulinemia (WM, n = 20) with healthy vaccine recipients (n = 37). Patient cohorts on active therapy affecting B cell development had impaired binding and neutralizing antibody (NAb) response rate and magnitude, including several patients lacking responses, even after a 3rd vaccine dose, whereas non-B cell depleting therapies had a lesser effect. In contrast, MM and WM cohorts off-therapy showed increased NAb with a broad response range. ELISA Spike-Receptor Binding Domain (RBD) Ab titers in healthy vaccine recipients and patient cohorts were good predictors of the ability to neutralize not only the original WA1 but also the most divergent Omicron variants BA.4/5. Compared to WA1, significantly lower NAb responses to BA.4/5 were found in all patient cohorts on-therapy. In contrast, the MM and WM cohorts off-therapy showed a higher probability to neutralize BA.4/5 after the 3rd vaccination. Overall, the boost in NAb after the 3rd dose suggests that repeat vaccination of MM and WM patients is beneficial even under active therapy. |
| first_indexed | 2024-03-09T17:52:05Z |
| format | Article |
| id | doaj.art-2e316c253ccd4d75b6a6ac9fa6c020af |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T17:52:05Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2e316c253ccd4d75b6a6ac9fa6c020af2023-11-24T10:39:07ZengMDPI AGCancers2072-66942022-11-011423581610.3390/cancers14235816Low Spike Antibody Levels and Impaired BA.4/5 Neutralization in Patients with Multiple Myeloma or Waldenstrom’s Macroglobulinemia after BNT162b2 Booster VaccinationMargherita Rosati0Evangelos Terpos1Jenifer Bear2Robert Burns3Santhi Devasundaram4Ioannis Ntanasis-Stathopoulos5Maria Gavriatopoulou6Efstathios Kastritis7Meletios-Athanasios Dimopoulos8George N. Pavlakis9Barbara K. Felber10Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USADepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 117 27 Athens, GreeceHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USAHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USAHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USADepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 117 27 Athens, GreeceDepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 117 27 Athens, GreeceDepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 117 27 Athens, GreeceDepartment of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 117 27 Athens, GreeceHuman Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USAHuman Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USAPatients with symptomatic monoclonal gammopathies have impaired humoral responses to COVID-19 vaccination. Their ability to recognize SARS-CoV-2 Omicron variants is of concern. We compared the response to BNT162b2 mRNA vaccinations of patients with multiple myeloma (MM, n = 60) or Waldenstrom’s macroglobulinemia (WM, n = 20) with healthy vaccine recipients (n = 37). Patient cohorts on active therapy affecting B cell development had impaired binding and neutralizing antibody (NAb) response rate and magnitude, including several patients lacking responses, even after a 3rd vaccine dose, whereas non-B cell depleting therapies had a lesser effect. In contrast, MM and WM cohorts off-therapy showed increased NAb with a broad response range. ELISA Spike-Receptor Binding Domain (RBD) Ab titers in healthy vaccine recipients and patient cohorts were good predictors of the ability to neutralize not only the original WA1 but also the most divergent Omicron variants BA.4/5. Compared to WA1, significantly lower NAb responses to BA.4/5 were found in all patient cohorts on-therapy. In contrast, the MM and WM cohorts off-therapy showed a higher probability to neutralize BA.4/5 after the 3rd vaccination. Overall, the boost in NAb after the 3rd dose suggests that repeat vaccination of MM and WM patients is beneficial even under active therapy.https://www.mdpi.com/2072-6694/14/23/5816COVID vaccinemultiple myelomaWaldenstrom’s macroglobulinemianeutralizationWA1BA.1 |
| spellingShingle | Margherita Rosati Evangelos Terpos Jenifer Bear Robert Burns Santhi Devasundaram Ioannis Ntanasis-Stathopoulos Maria Gavriatopoulou Efstathios Kastritis Meletios-Athanasios Dimopoulos George N. Pavlakis Barbara K. Felber Low Spike Antibody Levels and Impaired BA.4/5 Neutralization in Patients with Multiple Myeloma or Waldenstrom’s Macroglobulinemia after BNT162b2 Booster Vaccination Cancers COVID vaccine multiple myeloma Waldenstrom’s macroglobulinemia neutralization WA1 BA.1 |
| title | Low Spike Antibody Levels and Impaired BA.4/5 Neutralization in Patients with Multiple Myeloma or Waldenstrom’s Macroglobulinemia after BNT162b2 Booster Vaccination |
| title_full | Low Spike Antibody Levels and Impaired BA.4/5 Neutralization in Patients with Multiple Myeloma or Waldenstrom’s Macroglobulinemia after BNT162b2 Booster Vaccination |
| title_fullStr | Low Spike Antibody Levels and Impaired BA.4/5 Neutralization in Patients with Multiple Myeloma or Waldenstrom’s Macroglobulinemia after BNT162b2 Booster Vaccination |
| title_full_unstemmed | Low Spike Antibody Levels and Impaired BA.4/5 Neutralization in Patients with Multiple Myeloma or Waldenstrom’s Macroglobulinemia after BNT162b2 Booster Vaccination |
| title_short | Low Spike Antibody Levels and Impaired BA.4/5 Neutralization in Patients with Multiple Myeloma or Waldenstrom’s Macroglobulinemia after BNT162b2 Booster Vaccination |
| title_sort | low spike antibody levels and impaired ba 4 5 neutralization in patients with multiple myeloma or waldenstrom s macroglobulinemia after bnt162b2 booster vaccination |
| topic | COVID vaccine multiple myeloma Waldenstrom’s macroglobulinemia neutralization WA1 BA.1 |
| url | https://www.mdpi.com/2072-6694/14/23/5816 |
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