Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity against prevalent SARS-CoV-2 variants

Abstract

Background Heterologous 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. Methods To 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). Findings Self-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. Interpretation In 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. Funding This 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.

Immune response and safety of heterologous ChAdOx1-nCoV-19/mRNA-1273 vaccination compared with homologous ChAdOx1-nCoV-19 or homologous mRNA-1273 vaccination

“… 19 Similarly, a small German study that compared an 8-week interval of prime-boost ChAdOx1/BNT-162b2 with homologous BNT-162b2/BNT-162b2 vaccination found significantly higher neutralization titers against alpha variant and equivalent neutralizing activities against beta and delta variants. 20 Our study adds to the growing evidence that heterologous ChAdOx1/mRNA-1273 produces better neutralizing activities against both the alpha and delta variants than homologous ChAdOx1/ChAdOx1 vaccination when administered at 4-weeks or 8-weeks apart. Consistently, the analysis of spike-specific T cells and associated cytokines showed that the heterologous ChAdOx1/mRNA-1273 and the homologous mRNA-1273/mRNA-1273 vaccination stimulated more spike-specific cytokine-producing CD4 + T cells and more cytokine secretion than the homologous ChAdOx1/ChAdOx1 vaccination.…”

SARS-CoV-2 Spike and Neutralizing Antibody Kinetics 90 Days after Three Doses of BNT162b2 mRNA COVID-19 Vaccine in Singapore

“…Several studies have demonstrated a brisk antibody response to the booster vaccination [2][3][4][5], with some titers even higher than post-infection levels [3]. Booster vaccination has been shown to be effective against several different SARS-CoV-2 variants, including the new Omicron variant [6][7][8], and tolerated well with minimal side effects [9]. Indeed, booster vaccination regimens have been beneficial in controlling the spread of SARS-CoV-2, with real-world analysis [10] showing that it can reduce the rates of COVID-19 by a factor of 11.3, and severe illness by a factor of 19.5.…”

Duration of SARS-CoV-2 Immune Responses Up to Six Months Following Homologous or Heterologous Primary Immunization with ChAdOx1 nCoV-19 and BNT162b2 mRNA Vaccines

“…In the global struggle to achieve and maintain efficient COVID-19 vaccine programs, heterologous vaccine regimens attract great interest [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. With tolerable safety [ 1 , 8 , 9 ], and both immunogenicity [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 10 , 11 , 12 , 13 , 14 ] and effectiveness [ 15 , 16 , 17 , 18 , 19 , 20 ] exceeding that of homologous adenovector immunization, heterologous primary vaccination is as of 7 December 2021 recommended by European Medical Agency and European Centre for Disease prevention and Control [ 21 ]. However, more data on the duration of immune responses following heterologous primary vaccine protocols are needed [ 21 , 22 ].…”