Among the COVID-19-vaccines, the NVX-CoV2373-vaccine was the first protein-based vaccine that was licensed as a homologous dual dose regimen in the European Union and in the United States [1], [2], [3]. NVX-CoV2373 is a prefusion-stabilized recombinant spike protein subunit vaccine with a saponin-based matrix M adjuvant that conferred a 89.7-90.4% protection towards parental SARS-CoV-2 infection, with a good safety profile and high efficacy against the B.1.1.7 variant [4, 5]. The efficacy exceeded those of the vector-based vaccines and was in a similar range as the two mRNA-based vaccines BNT162b2 and mRNA-1273, which were shown to be 95.0% and 94.1% efficacious, respectively, at preventing severe COVID-19 illness from the parental viral strains [6, 7].

The immunogenicity of the two mRNA-vaccines has been extensively characterized in real world settings, and both vaccines induce strong antibody and T-cell responses [8, 9]. Likewise, the phase 1-2 trial of the NVX-CoV2373-vaccine or a recent phase III trial has shown induction of high antibody titers [10, 11], and first data on neutralizing activity towards SARS-CoV-2 variants of concern (VOCs) from participants of the pivotal trial 3-4 months after the second dose became available recently [12], [13], [14]. However, real world data on the immunogenicity of the NVX-CoV2373-vaccine during the induction phase, especially regarding its ability to induce CD4 and CD8 T-cells and in comparison to other licensed vaccines are currently lacking. Given the fact that the vaccine was licensed during the surge of the Delta and the Omicron wave with its subvariants that are known to escape neutralizing antibody activity, knowledge of cellular immunity and its reactivity towards VOCs is of particular importance to inform on the ability to confer protection from severe disease.

We therefore carried out an observational study on the immunogenicity and reactogenicity of the NVX-CoV2373-vaccine in immunocompetent individuals who were vaccinated when the vaccine became approved and recommended in Germany [2]. Apart from vaccine-related adverse events, we characterized the induction of spike-specific IgG as well as CD4 and CD8 T-cells including humoral and cellular reactivity towards the parental SARS-CoV-2 and variants of concern. Moreover, immune-responses after two doses of the vaccine were compared with respective data from matched cohorts of mRNA-vaccinated individuals.