Matthias Proffen (Ulm/ DE), Carolin Ludwig (Ulm/ DE), Judith Scholz (Ulm/ DE), Janina Hägele (Ulm/ DE), Christine Vieweg (Ulm/ DE), Prof. Dr. Ramin Lotfi (Ulm/ DE), Dr. Sixten Körper (Ulm/ DE), Prof. Dr. Hubert Schrezenmeier (Ulm/ DE), PD Dr. Dorit Fabricius (Ulm/ DE), Prof. Dr. Bernd Jahrsdörfer (Ulm/ DE)
Background
Recently, we demonstrated that heterologous vaccination regimes against COVID-19, which consisted of a combination of the vector vaccine ChAdOx1 from AstraZeneca and either the mRNA vaccine BNT162b2 from BioNTech or Spikevax from Moderna, resulted in significantly enhanced serological and cellular immune responses against SARS-CoV-2 after second vaccination.
Methods
In the present follow-up study, we continued to analyze anti-SARS-CoV-2 antibody titers, neutralization capacities against the wildtype virus and the variant of concern (VOC) Omicron BA.1, as well as IFN-g responses against the spike protein up to 6 months after booster vaccination. In addition, applying FACS analysis and cell culture studies using SARS-CoV-2-specific peptides (Novavax), we investigated the potential role of two important antigen-presenting cell types, which circulate in the peripheral blood (plasmacytoid dendritic cells (pDC) and B cells), for the immune response after vaccination.
Results
One month after booster vaccination, up to 91% of all donors from vaccination regimes containing two or three mRNA doses exhibited detectable Omicron neutralization capacity (Figure 1). Furthermore, we found a stable frequency and expression of antigen-presenting and co-stimulatory molecules on CD19+ B cells up to 3 months after booster vaccination, regardless of the vaccination regime. In pDCs in contrast, we observed a trend for increasing expression of MHC class II and CD40L even after booster vaccination, suggesting an ongoing role in antigen presentation. Performing functional pulsing studies with pDCs and SARS-CoV-2 peptide (Novavax), we demonstrated that pDCs are involved in the presentation of these peptides to T cells (Figure 2).
Conclusion
In summary, our follow-up study demonstrates that effective neutralizing and cellular immunity against SARS-CoV-2 is associated with the activation of both B cells and pDCs, and that pDCs are functionally involved in antigen presentation after vaccination. Furthermore, our follow-up data up to 6 months after booster vaccination suggests no significant differences in serological and cellular response parameters between vaccination groups, as long as two or three mRNA doses are included.
Offenlegung Interessenkonflikt:
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