Artikel
Pre-exposure prophylaxis using SARS-CoV-2 neutralizing antibodies suppresses the specific cellular immune response to mRNA vaccination in rheumatic patients
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Veröffentlicht: | 31. August 2022 |
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Introduction: Active and passive immunizations against SARS-CoV-2 are used to protect against the development of severe COVID-19. However, the effect of passive immunization on the success of a subsequent active vaccination is unknown. Here, we investigate the cellular immune response to mRNA vaccination against SARS-CoV-2 in patients receiving preventive treatment with a SARS-CoV-2 neutralizing antibody cocktail, Ronapreve (Casirivimab/Imdevimab).
Methods: After poorly responding to multiple mRNA vaccinations against SARS-CoV-2, four patients with different autoimmune diseases treated with immunosuppressants including rituximab received 600 mg Ronapreve i.v. and were re-vaccinated 14-25 days later. Eleven clinically comparable patients served as controls. All participants were re-immunized with the mRNA-based Spikevax vaccine. Antigen-specific T- and B-cell responses were assessed by flow cytometry, after short-term stimulation with spike peptides and tetramer staining for spike-specific B cells before, 1 week, and 4 weeks after vaccination.
Results: As expected, most control patients showed a specific CD4 T- and B-cell response in the blood after vaccination, including induction of antigen-specific plasmablasts at week 1 and a significant increase of antigen-specific CD4 T cells producing IFNγ, IL-4, or IL-10 at week 4. In patients receiving Ronapreve, the induction of plasmablasts in the blood was effectively suppressed but not completely eliminated. In contrast to control patients, there was no consistent increase in SARS-CoV-2-specific CD4 T cells in Ronapreve-treated patients. Our data indicate that passive immunization effectively inhibits the cellular immune response to active vaccination.
Conclusion: The timing of active and passive immunizations to homologous antigen in the same patient requires consideration. The benefit of pre- or post-exposure prophylaxis by neutralizing antibodies must be weighed against the risk of ineffective vaccination.
Disclosures: All authors indicate that they have no conflict of interest.