Dynamics of Humoral and Cellular Immune Responses after Homologous and Heterologous SARS-CoV-2 Vaccination with ChAdOx1 Ncov-19 and BNT162b2

Background Vaccines are an important means to overcome the SARS-CoV-2 pandemic. They induce specific anti-body and T-cell responses but it remains open how well vaccine-induced immunity is preserved over time following homologous and heterologous immunization regimens. Here, we compared the dynamics of humoral and cellular immune responses up to 180 days after homologous or heterologous vaccination with either ChAdOx1-nCoV-19 (ChAd) or BNT162b2 (BNT) or both.Methods Various tests were used to determine the humoral and cellular immune response. To quantify the antibody levels, we used the surrogate neutralization (sVNT) assay from YHLO, which we augmented with pseudo-and real virus neutralization tests (pVNT and rVNT). Antibody avidity was measured by a modified ELISA. To determine cel-lular reactivity, we used an IFN-g Elispot, IFN-g/IL Flurospot, and intracellular cytokine staining.Findings Antibody responses significantly waned after vaccination, irrespective of the regimen. The capacity to neu-tralize SARS-CoV-2 -including variants of concern such as Delta or Omicron -was superior after heterologous compared to homologous BNT vaccination, both of which resulted in longer-lasting humoral immunity than homol-ogous ChAd immunization. All vaccination regimens induced stable, polyfunctional T-cell responses. Interpretation These findings demonstrate that heterologous vaccination with ChAd and BNT is a potent alternative to induce humoral and cellular immune protection in comparison to the homologous vaccination regimens.Copyright (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)