Abstract
SummaryBackgroundHeterologous COVID-19 vaccination regimens combining vector- and mRNA-based vaccines are already administered, but data on solicited adverse reactions, immunological responses and elicited protection are limited.MethodsTo evaluate the reactogenicity and humoral as well as cellular immune responses towards most prevalent SARS-CoV-2 variants after a heterologous ChAdOx1 nCoV-19 BNT162b2 prime-boost vaccination, we analysed a cohort of 26 clinic employees aged 25-46 (median 30.5) years who received a ChAdOx1 nCoV-19 prime followed by a BNT162b2 boost after an 8-week interval. Serological data were compared to a cohort which received homologous BNT162b2 vaccination with a 3-week interval (14 individuals aged 25-65, median 42).FindingsSelf-reported solicited symptoms after ChAdOx1 nCoV-19 prime were in line with previous reports and more severe than after the BNT162b2 boost. Antibody titres increased significantly over time resulting in strong neutralization titres two weeks after the BNT162b2 boost and subsequently slightly decreased over the course of 17 weeks. At the latest time point measured, all analysed sera retained neutralizing activity against the currently dominant Delta (B.1.617.2) variant. Two weeks post boost, neutralizing activity against the Alpha (B.1.1.7) and immune-evading Beta (B.1.351) variant was ∼4-fold higher than in individuals receiving homologous BNT162b2 vaccination. No difference was observed in neutralization of Kappa (B.1.617.1). In addition, heterologous vaccination induced CD4+ and CD8+ T cells reactive to SARS-CoV-2 spike peptides of all analysed variants; Wuhan-Hu-1, Alpha, Beta, Gamma (P.1), and Delta.InterpretationIn conclusion, heterologous ChAdOx1 nCoV-19 / BNT162b2 prime-boost vaccination is not associated with serious adverse events and induces potent humoral and cellular immune responses. The Alpha, Beta, Delta, and Kappa variants of spike are potently neutralized by sera from all participants and reactive T cells recognize spike peptides of all tested variants. These results suggest that this heterologous vaccination regimen is at least as immunogenic and protective as homologous vaccinations and also offers protection against current variants of concern.FundingThis project has received funding from the European Union's Horizon 2020 research and innovation programme, the German Research Foundation, the BMBF, the Robert Koch Institute (RKI), the Baden-Württemberg Stiftung, the county of Lower Saxony, the Ministry for Science, Research and the Arts of Baden-Württemberg, Germany, and the National Institutes of Health.
Highlights
The first cases of the coronavirus disease 2019 (COVID19) were reported to the World Health Organization on December 31st 2019,1 and within 93 days the causative severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) had infected over 1 million people worldwide.[2]Only 250 days later, the first person received a COVID-19 vaccine outside a clinical trial
While robust immune responses are elicited by heterologous vaccination regimens with a 8-12 week interval,17À19,21 there is limited knowledge about humoral and cellular protection against the variants of concern (VOCs), especially the most prevalent Delta (B.1.617.2) variant.19,21À23 Further, published studies have not investigated how immunity develops several months after vaccination
Study Design A cohort of 26 individuals aged 25-46 years who received a ChAdOx1 nCoV-19 prime followed by a BNT162b2 boost after an 8-week interval were analysed for reactogenicity, antibody responses and T cell reactivity
Summary
The first cases of the coronavirus disease 2019 (COVID19) were reported to the World Health Organization on December 31st 2019,1 and within 93 days the causative severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) had infected over 1 million people worldwide.[2]Only 250 days later, the first person received a COVID-19 vaccine outside a clinical trial. ChAdOx1 nCoV-19 vaccinations, especially in individuals younger than 60 years, associated with the generation of auto-platelet factor 4 antibodies, halted vaccination of this group with ChAdOx1 nCoV-19 in some countries.13À15 As a consequence, several public health agencies recommended boost vaccinations of individuals already primed with ChAdOx1 nCoV-19 to be carried out in a heterologous regimen with an mRNA vaccine.[16] In some countries, such a regimen is still not applied due to limited data on safety and immunogenicity. While robust immune responses are elicited by heterologous vaccination regimens with a 8-12 week interval,17À19,21 there is limited knowledge about humoral and cellular protection against the variants of concern (VOCs), especially the most prevalent Delta (B.1.617.2) variant.19,21À23 Further, published studies have not investigated how immunity develops several months after vaccination
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