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Although all individuals had no known history of SARS-CoV-2 infection, three tested positive for SARS-CoV-2 nucleocapsid (N)-specific IgG and were excluded from further analyses. Blood samples were drawn at a median of 14 (interquartile range (IQR) = 2) days after vaccination. As per guidelines, the time between primary and secondary vaccination was shorter for mRNA-primed (4.3 ± 1.1 weeks) than for vector-primed individuals, with no difference between vector-based heterologous (11.2 ± 1.3 weeks) and homologous regimens (10.8 ± 1.4 weeks). Ninety-seven study participants received heterologous vaccination with the ChAdOx1 vector and mRNA booster (vector/mRNA), whereas 55 and 64 received homologous regimens with vector or mRNA vaccine, respectively (vector/vector and mRNA/mRNA Extended Data Fig. Adverse events within the first week after the priming and booster doses were self-reported based on a standardized questionnaire.Ī total of 216 immunocompetent individuals, primarily comprising employees, were prospectively enrolled at Saarland University Medical Center before secondary vaccination with the authorized vaccines ChAdOx1 nCoV-19, BNT162b2 or mRNA-1273 ( Methods). In addition, spike-specific CD4 and CD8 T cells were characterized using flow cytometry. A detailed analysis of spike-specific IgG levels and neutralizing antibody activity was performed. We therefore prospectively enrolled three groups of individuals to study the immunogenicity and reactogenicity of a heterologous vector/mRNA prime–booster regimen in comparison to the standard homologous regimens. We hypothesized that differences among the vaccine types after priming may influence cellular and humoral immunity following secondary vaccination. We have found that priming with the ChAdOx1 vaccine showed a stronger induction of spike-specific T cell responses as compared to mRNA priming, while antibody responses were more pronounced after mRNA priming 7. Comparative analyses of immunogenicity between the authorized vaccine regimens are scarce, and knowledge on immunity and reactogenicity after heterologous vaccination is currently limited. Individuals above the age of 60 years are recommended to complete vaccination with the vector vaccine, whereas heterologous boosting with an mRNA vaccine is recommended in those <60 years, with the option to voluntarily remain on a homologous vector regimen 6. This resulted in revised recommendations for secondary vaccination of all individuals who had received the first dose of the vaccine 6. In March 2021, administration of the ChAdOx1 vaccine was temporarily suspended in Germany due to the occurrence of life-threatening cerebral venous thrombosis and thrombocytopenia, primarily in younger women 4, 5. Both vaccine types are immunogenic and have shown remarkable efficacy in preventing COVID-19 disease 1, 2, 3.
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Taken together, heterologous vector/mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profiles.Īmong the currently authorized COVID-19 vaccines, the ChAdOx1 nCoV-19 adenovirus-based vector vaccine (ChAdOx1) and the two mRNA vaccines (BNT162b2 and mRNA-1273) have been the most widely used. Recipients of both the homologous vector regimen and the heterologous vector/mRNA combination reported greater reactogenicity following the priming vector vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA boosting. Spike-specific T cells were predominantly polyfunctional with largely overlapping cytokine-producing phenotypes in all three regimens. Moreover, spike-specific CD8 T cell levels after heterologous vaccination were significantly higher than after both homologous regimens. In this observational study we show that, in healthy adult individuals ( n = 96), the heterologous vaccine regimen induced spike-specific IgG, neutralizing antibodies and spike-specific CD4 T cells, the levels of which which were significantly higher than after homologous vector vaccine boost ( n = 55) and higher or comparable in magnitude to homologous mRNA vaccine regimens ( n = 62). Heterologous priming with the ChAdOx1 nCoV-19 vector vaccine followed by boosting with a messenger RNA vaccine (BNT162b2 or mRNA-1273) is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available.