Humoral and cellular immune responses and their kinetics vary in dependence of diagnosis and treatment in immunocompromised patients upon COVID-19 mRNA vaccination

  1. A. Wagner
  2. E. Garner-Spitzer
  3. A. Schötta
  4. M. Orola
  5. A. Wessely
  6. I. Zwazl
  7. A. Ohradanova-Repic
  8. G. Tajti
  9. L. Gebetsberger
  10. B. Kratzer
  11. E. Tomosel
  12. M. Kutschera
  13. S. Tobudic
  14. W. F. Pickl
  15. M. Kundi
  16. H. Stockinger
  17. G. Novacek
  18. W. Reinisch
  19. C Zielinski
  20. U. Wiedermann
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Abstract

Background

Knowledge about humoral and cellular immunogenicity and their kinetics following SARS-CoV-2 mRNA vaccinations in immunosuppressed patients is limited.

Methods

Antibody and cytokine responses were assessed in 263 patients with either solid tumors (SOT, n=63), multiple myeloma (MM, n=70) or inflammatory bowel diseases (IBD, n=130) undergoing various immunosuppressive regimens and from 66 healthy controls before the first and the second, as well as four weeks and 5-6 months after the second mRNA vaccine dose with either BNT162b2 or mRNA-1273.

Findings

Four weeks after the second dose, seroconversion was lower in cancer than in IBD patients and controls, with the highest non-responder rate in MM patients (17.1%). S1-specific IgG levels correlated with neutralizing antibody titers. While antibody responses correlated with cellular responses in controls and IBD patients, IFN-γ and antibody responses did not in SOT and MM patients. At six months, 19.6% of patients with MM and 7.3% with SOT had become seronegative, while IBD patients and controls remained seropositive in 96.3% and 100%, respectively. Vaccinees receiving mRNA-1273 presented higher antibody levels than those vaccinated with BNT162b2.

Interpretation

Cancer patients may launch an inadequate seroresponse in the immediate time range following vaccination and up to six months, correlating with vaccine-specific cellular responses. These findings propose antibody testing in immunosuppressed - along with cellular testing - provides guidance for administration of additional vaccine doses, or may indicate the necessity for antibody treatment. IBD patients respond well to the vaccine, but treatment such as with TNF-α inhibitors may reduce persistence of immune responses.

Funding

The study was sponsored and financed by the Medical University of Vienna – third party funding by the Institute of Specific Prophylaxis and Tropical Medicine. AOR. and HS acknowledge funding by the Austrian Science Fund (FWF, P 34253-B).

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