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

Front Immunol2022 May 12;13:889138.doi: 10.3389/fimmu.2022.889138.eCollection 2022.


Angelika Wagner 1Erika Garner-Spitzer 1Anna-Margarita Schötta 2Maria Orola 1Andrea Wessely 1Ines Zwazl 1Anna Ohradanova-Repic 2Lukas Weseslindtner 3Gabor Tajti 2Laura Gebetsberger 2Bernhard Kratzer 4Elena Tomosel 1Maximilian Kutschera 5Selma Tobudic 6Winfried F Pickl 4Michael Kundi 7Hannes Stockinger 2Gottfried Novacek 5Walter Reinisch 5Christoph Zielinski 8 9Ursula Wiedermann 1


Author information

1Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, Austria.

2Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, Austria.

3Center for Virology, Medical University of Vienna, Vienna, Austria.

4Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, Austria.

5Department of Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Vienna, Austria.

6Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.

7Center for Public Health, Medical University Vienna, Vienna, Austria.

8Central European Cancer Center, Wiener Privatklinik, Vienna, Austria.

9The Central European Cancer Center, Central European Cooperative Oncology Group, Headquater (HQ), Vienna, Austria.


Background: Individuals 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.

Methods: In 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.

Results: 263 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.

Conclusion: Immunomonitoring 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 registration: EudraCT Number: 2021-000291-11.


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