ABSTRACT
Vaccines are the most 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 5 months after homologous or heterologous vaccination with either ChAdOx1-nCoV-19 (ChAd) or BNT162b2 (BNT) or both. 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. T-cell responses showed less waning irrespective of the vaccination regimen. These findings demonstrate that heterologous vaccination with ChAd and BNT is a potent approach to induce long-term humoral and cellular immune protection.