Elsevier

eBioMedicine

Volume 85, November 2022, 104294
eBioMedicine

Articles
Dynamics of humoral and cellular immune responses after homologous and heterologous SARS-CoV-2 vaccination with ChAdOx1 nCoV-19 and BNT162b2

https://doi.org/10.1016/j.ebiom.2022.104294Get rights and content
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Summary

Background

Vaccines are an important means to overcome the SARS-CoV-2 pandemic. They induce specific antibody 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 cellular reactivity, we used an IFN-γ Elispot, IFN-γ/IL Flurospot, and intracellular cytokine staining.

Findings

Antibody responses significantly waned after vaccination, irrespective of the regimen. The capacity to neutralize 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 homologous 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.

Funding

The study was funded by the German Centre for Infection Research (DZIF), the European Union's “Horizon 2020 Research and Innovation Programme" under grant agreement No. 101037867 (VACCELERATE), the “Bayerisches Staatsministerium für Wissenschaft und Kunst” for the CoVaKo-2021 and the For-COVID projects and the Helmholtz Association via the collaborative research program “CoViPa”. Further support was obtained from the Federal Ministry of Education and Science (BMBF) through the “Netzwerk Universitätsmedizin”, project “B-Fast” and “Cov-Immune”. KS is supported by the German Federal Ministry of Education and Research (BMBF, 01KI2013) and the Else Kröner-Stiftung (2020_EKEA.127).

Keywords

Heterologous vaccination
COVID-19
vaccine
BNT162b2
ChAdOx1-nCoV-19
SARS-CoV-2
long-term
maintenance
T cell immunity
antibody avidity

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These authors contributed equally.