The type of the first prime/boost vaccine against SARS-CoV-2 exerts long-term effects on the humoral immune response

The outbreak of COVID-19 spurred the development of different vaccines against SARS-CoV-2 however, recommendations on how to maintain long-term protection from COVID-19 remain elusive. We here report on a cohort of 192 health care workers receiving their primary vaccination with either AZD1222 or BNT162b2. Over the course of three years, six blood samples were taken and analyzed for antibody dynamics against the receptor binding domain of the Spike protein and for function via surrogate virus neutralization. Our results showed that higher anti SARS-CoV-2 S titers correlated with increased neutralizing capacity and ameliorated COVID-19 disease. The type of the first prime/boost vaccine exerted long term effects with a homologous BNT162b2 regimen outperforming AZD1222 in terms of antibody titers and neutralizing capacity. This deficit for AZD1222 was not compensated for by subsequent boosting with RNA vaccines, was still evident after three years, and is discussed in the context of immune imprinting.