SARS-CoV-2-mRNA Booster Vaccination Reverses Non-Responsiveness and Early Antibody Waning in Immunocompromised Patients – A Phase Four Study Comparing Immune Responses in Patients With Solid Cancers, Multiple Myeloma and Inflammatory Bowel Disease
BackgroundIndividuals with secondary immunodeficiencies belong to the most vulnerable groups to succumb to COVID-19 and thus are prioritized for SARS-CoV-2 vaccination. However, knowledge about the persistence and anamnestic responses following SARS-CoV-2-mRNA vaccinations is limited in these patien...
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.889138/full |
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| author | Angelika Wagner Erika Garner-Spitzer Anna-Margarita Schötta Maria Orola Andrea Wessely Ines Zwazl Anna Ohradanova-Repic Lukas Weseslindtner Gabor Tajti Laura Gebetsberger Bernhard Kratzer Elena Tomosel Maximilian Kutschera Selma Tobudic Winfried F. Pickl Michael Kundi Hannes Stockinger Gottfried Novacek Walter Reinisch Christoph Zielinski Christoph Zielinski Ursula Wiedermann |
| author_facet | Angelika Wagner Erika Garner-Spitzer Anna-Margarita Schötta Maria Orola Andrea Wessely Ines Zwazl Anna Ohradanova-Repic Lukas Weseslindtner Gabor Tajti Laura Gebetsberger Bernhard Kratzer Elena Tomosel Maximilian Kutschera Selma Tobudic Winfried F. Pickl Michael Kundi Hannes Stockinger Gottfried Novacek Walter Reinisch Christoph Zielinski Christoph Zielinski Ursula Wiedermann |
| author_sort | Angelika Wagner |
| collection | DOAJ |
| description | BackgroundIndividuals with secondary immunodeficiencies belong to the most vulnerable groups to succumb to COVID-19 and thus are prioritized for SARS-CoV-2 vaccination. However, knowledge about the persistence and anamnestic responses following SARS-CoV-2-mRNA vaccinations is limited in these patients.MethodsIn a prospective, open-label, phase four trial we analyzed S1-specific IgG, neutralizing antibodies and cytokine responses in previously non-infected patients with cancer or autoimmune disease during primary mRNA vaccination and up to one month after booster.Results263 patients with solid tumors (SOT, n=63), multiple myeloma (MM, n=70), inflammatory bowel diseases (IBD, n=130) and 66 controls were analyzed. One month after the two-dose primary vaccination the highest non-responder rate was associated with lower CD19+ B-cell counts and was found in MM patients (17%). S1-specific IgG levels correlated with IL-2 and IFN-γ responses in controls and IBD patients, but not in cancer patients. Six months after the second dose, 18% of patients with MM, 10% with SOT and 4% with IBD became seronegative; no one from the control group became negative. However, in IBD patients treated with TNF-α inhibitors, antibody levels declined more rapidly than in controls. Overall, vaccination with mRNA-1273 led to higher antibody levels than with BNT162b2. Importantly, booster vaccination increased antibody levels >8-fold in seroresponders and induced anamnestic responses even in those with undetectable pre-booster antibody levels. Nevertheless, in IBD patients with TNF-α inhibitors even after booster vaccination, antibody levels were lower than in untreated IBD patients and controls.ConclusionImmunomonitoring of vaccine-specific antibody and cellular responses seems advisable to identify vaccination failures and consequently establishing personalized vaccination schedules, including shorter booster intervals, and helps to improve vaccine effectiveness in all patients with secondary immunodeficiencies.Trial registrationEudraCT Number: 2021-000291-11 |
| first_indexed | 2024-04-14T00:36:44Z |
| format | Article |
| id | doaj.art-46a9474201d04a2d8417d87fcf0f565a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-14T00:36:44Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-46a9474201d04a2d8417d87fcf0f565a2022-12-22T02:22:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-05-011310.3389/fimmu.2022.889138889138SARS-CoV-2-mRNA Booster Vaccination Reverses Non-Responsiveness and Early Antibody Waning in Immunocompromised Patients – A Phase Four Study Comparing Immune Responses in Patients With Solid Cancers, Multiple Myeloma and Inflammatory Bowel DiseaseAngelika Wagner0Erika Garner-Spitzer1Anna-Margarita Schötta2Maria Orola3Andrea Wessely4Ines Zwazl5Anna Ohradanova-Repic6Lukas Weseslindtner7Gabor Tajti8Laura Gebetsberger9Bernhard Kratzer10Elena Tomosel11Maximilian Kutschera12Selma Tobudic13Winfried F. Pickl14Michael Kundi15Hannes Stockinger16Gottfried Novacek17Walter Reinisch18Christoph Zielinski19Christoph Zielinski20Ursula Wiedermann21Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, AustriaInstitute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, AustriaInstitute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, AustriaInstitute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, AustriaInstitute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, AustriaInstitute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, AustriaInstitute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, AustriaCenter for Virology, Medical University of Vienna, Vienna, AustriaInstitute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, AustriaInstitute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, AustriaInstitute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, AustriaInstitute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, AustriaDepartment of Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Vienna, AustriaDepartment of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, AustriaInstitute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, AustriaCenter for Public Health, Medical University Vienna, Vienna, AustriaInstitute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, AustriaDepartment of Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Vienna, AustriaDepartment of Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Vienna, AustriaCentral European Cancer Center, Wiener Privatklinik, Vienna, AustriaThe Central European Cancer Center, Central European Cooperative Oncology Group, Headquater (HQ), Vienna, AustriaInstitute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, AustriaBackgroundIndividuals with secondary immunodeficiencies belong to the most vulnerable groups to succumb to COVID-19 and thus are prioritized for SARS-CoV-2 vaccination. However, knowledge about the persistence and anamnestic responses following SARS-CoV-2-mRNA vaccinations is limited in these patients.MethodsIn a prospective, open-label, phase four trial we analyzed S1-specific IgG, neutralizing antibodies and cytokine responses in previously non-infected patients with cancer or autoimmune disease during primary mRNA vaccination and up to one month after booster.Results263 patients with solid tumors (SOT, n=63), multiple myeloma (MM, n=70), inflammatory bowel diseases (IBD, n=130) and 66 controls were analyzed. One month after the two-dose primary vaccination the highest non-responder rate was associated with lower CD19+ B-cell counts and was found in MM patients (17%). S1-specific IgG levels correlated with IL-2 and IFN-γ responses in controls and IBD patients, but not in cancer patients. Six months after the second dose, 18% of patients with MM, 10% with SOT and 4% with IBD became seronegative; no one from the control group became negative. However, in IBD patients treated with TNF-α inhibitors, antibody levels declined more rapidly than in controls. Overall, vaccination with mRNA-1273 led to higher antibody levels than with BNT162b2. Importantly, booster vaccination increased antibody levels >8-fold in seroresponders and induced anamnestic responses even in those with undetectable pre-booster antibody levels. Nevertheless, in IBD patients with TNF-α inhibitors even after booster vaccination, antibody levels were lower than in untreated IBD patients and controls.ConclusionImmunomonitoring of vaccine-specific antibody and cellular responses seems advisable to identify vaccination failures and consequently establishing personalized vaccination schedules, including shorter booster intervals, and helps to improve vaccine effectiveness in all patients with secondary immunodeficiencies.Trial registrationEudraCT Number: 2021-000291-11https://www.frontiersin.org/articles/10.3389/fimmu.2022.889138/fullpatients under immunosuppression/immunomodulationSARS-CoV-2 mRNA vaccinationbooster vaccinationhumoral and cellular vaccine-specific responsesantibody testingwaning of immune responses |
| spellingShingle | Angelika Wagner Erika Garner-Spitzer Anna-Margarita Schötta Maria Orola Andrea Wessely Ines Zwazl Anna Ohradanova-Repic Lukas Weseslindtner Gabor Tajti Laura Gebetsberger Bernhard Kratzer Elena Tomosel Maximilian Kutschera Selma Tobudic Winfried F. Pickl Michael Kundi Hannes Stockinger Gottfried Novacek Walter Reinisch Christoph Zielinski Christoph Zielinski Ursula Wiedermann SARS-CoV-2-mRNA Booster Vaccination Reverses Non-Responsiveness and Early Antibody Waning in Immunocompromised Patients – A Phase Four Study Comparing Immune Responses in Patients With Solid Cancers, Multiple Myeloma and Inflammatory Bowel Disease Frontiers in Immunology patients under immunosuppression/immunomodulation SARS-CoV-2 mRNA vaccination booster vaccination humoral and cellular vaccine-specific responses antibody testing waning of immune responses |
| title | SARS-CoV-2-mRNA Booster Vaccination Reverses Non-Responsiveness and Early Antibody Waning in Immunocompromised Patients – A Phase Four Study Comparing Immune Responses in Patients With Solid Cancers, Multiple Myeloma and Inflammatory Bowel Disease |
| title_full | SARS-CoV-2-mRNA Booster Vaccination Reverses Non-Responsiveness and Early Antibody Waning in Immunocompromised Patients – A Phase Four Study Comparing Immune Responses in Patients With Solid Cancers, Multiple Myeloma and Inflammatory Bowel Disease |
| title_fullStr | SARS-CoV-2-mRNA Booster Vaccination Reverses Non-Responsiveness and Early Antibody Waning in Immunocompromised Patients – A Phase Four Study Comparing Immune Responses in Patients With Solid Cancers, Multiple Myeloma and Inflammatory Bowel Disease |
| title_full_unstemmed | SARS-CoV-2-mRNA Booster Vaccination Reverses Non-Responsiveness and Early Antibody Waning in Immunocompromised Patients – A Phase Four Study Comparing Immune Responses in Patients With Solid Cancers, Multiple Myeloma and Inflammatory Bowel Disease |
| title_short | SARS-CoV-2-mRNA Booster Vaccination Reverses Non-Responsiveness and Early Antibody Waning in Immunocompromised Patients – A Phase Four Study Comparing Immune Responses in Patients With Solid Cancers, Multiple Myeloma and Inflammatory Bowel Disease |
| title_sort | sars cov 2 mrna booster vaccination reverses non responsiveness and early antibody waning in immunocompromised patients a phase four study comparing immune responses in patients with solid cancers multiple myeloma and inflammatory bowel disease |
| topic | patients under immunosuppression/immunomodulation SARS-CoV-2 mRNA vaccination booster vaccination humoral and cellular vaccine-specific responses antibody testing waning of immune responses |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.889138/full |
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