Heterologous prime–boost vaccination with ChAdOx1 nCoV-19 and BNT162b2

Tenbusch, Matthias; Schumacher, Sofie; Vogel, Emanuel; Priller, Alina; Held, Jürgen; Steininger, Philipp; Beileke, Stephanie; Irrgang, Pascal; Brockhoff, Ronja; Salmanton‐García, Jon; Tinnefeld, Kathrin; Mijočević, Hrvoje; Schober, Kilian; Bogdan, Christian; Yazici, Sarah; Knolle, Percy; Cornely, Oliver A.; Überla, Klaus; Protzer, Ulrike; Roggendorf, Hedwig; Zelger, Otto; Christa, Catharina; Jeske, Samuel; Heringer, Sarah; Alsalameh, Rayya J.; Esse, Jan; Mattner, Jochen; Wytopil, Monika

doi:10.1016/s1473-3099(21)00420-5

Cited by 119 publications

(127 citation statements)

References 5 publications

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“…Yhlo-NAb is based on the competition of the patient's serum antibodies with recombinant angiotensin-converting-enzyme 2 for binding to the SARS-CoV-2 spike protein receptor-binding domain. The results of DiaSorin-IgG and Yhlo-NAb correlate closely with the conventional wild-type SARS-CoV-2 neutralization assays [20]. All assays were performed according to the manufacturers' recommendations on automated platforms (Euroimmun Analyzer I, Vircell ThunderBolt, LIAISON XL and iFlash 1800 CLIA).…”

Section: Methodsmentioning

confidence: 65%

Reactogenicity Correlates Only Weakly with Humoral Immunogenicity after COVID-19 Vaccination with BNT162b2 mRNA (Comirnaty®)

et al. 2021

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mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), such as BNT162b2 (Comirnaty®), have proven to be highly immunogenic and efficient but also show marked reactogenicity, leading to adverse effects (AEs). Here, we analyzed whether the severity of AEs predicts the antibody response against the SARS-CoV-2 spike protein. Healthcare workers without prior SARS-CoV-2 infection, who received a prime-boost vaccination with BNT162b2, completed a standardized electronic questionnaire on the duration and severity of AEs. Serum specimens were collected two to four weeks after the boost vaccination and tested with the COVID-19 ELISA IgG (Vircell-IgG), the LIAISON® SARS-CoV-2 S1/S2 IgG CLIA (DiaSorin-IgG) and the iFlash-2019-nCoV NAb surrogate neutralization assay (Yhlo-NAb). A penalized linear regression model fitted by machine learning was used to correlate AEs with antibody levels. Eighty subjects were enrolled in the study. Systemic, but not local, AEs occurred more frequently after the boost vaccination. Elevated SARS-CoV-2 IgG antibody levels were measured in 92.5% of subjects with Vircell-IgG and in all subjects with DiaSorin-IgG and Yhlo-NAb. Gender, age and BMI showed no association with the antibody levels or with the AEs. The linear regression model identified headache, malaise and nausea as AEs with the greatest variable importance for higher antibody levels (Vircell-IgG and DiaSorin-IgG). However, the model performance for predicting antibody levels from AEs was very low for Vircell-IgG (squared correlation coefficient r2 = 0.04) and DiaSorin-IgG (r2 = 0.06). AEs did not predict the surrogate neutralization (Yhlo-NAb) results. In conclusion, AEs correlate only weakly with the SARS-CoV-2 spike protein antibody levels after COVID-19 vaccination with BNT162b2 mRNA.

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Section: Methodsmentioning

confidence: 65%

Reactogenicity Correlates Only Weakly with Humoral Immunogenicity after COVID-19 Vaccination with BNT162b2 mRNA (Comirnaty®)

et al. 2021

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“…Currently approved vector and mRNA vaccination strategies against SARS-CoV-2 consider only homologous vaccination. However, recent studies indicate a better humoral and cellular immune response after heterologous prime-boost vaccination in healthy individuals 16,[18][19][20][21] . In our study, no significant advantage for either the homologous or heterologous vaccination strategy was found: the primary outcome showed a 10% higher seroconversion rate for mRNA (homologous) versus vector (heterologous) vaccination.…”

Section: Discussionmentioning

confidence: 99%

Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomized controlled trial

Bonelli

Mrak

Tobudic

et al. 2021

Preprint

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Severe acute respiratory syndrome coronavirus–2 (SARS–CoV–2)–induced coronavirus disease 2019 (COVID–19) has led to exponentially rising mortality, particularly in immunosuppressed patients, who inadequately respond to conventional COVID–19 vaccination. In this blinded randomized clinical trial (EudraCT 2021–002348–57) we compare the efficacy and safety of an additional booster vaccination with a vector versus mRNA vaccine in non–seroconverted patients. We assigned 60 patients under rituximab treatment, who did not seroconvert after their primary mRNA vaccination with either BNT162b2 (Pfizer–BioNTech) or mRNA–1273 (Moderna), to receive a third dose, either using the same mRNA or the vector vaccine ChAdOx1 nCoV–19 (Oxford–AstraZeneca). Patients were stratified according to the presence of peripheral B–cells. The primary efficacy endpoint was the difference in the SARS–CoV–2 antibody seroconversion rate between vector (heterologous) and mRNA (homologous) vaccinated patients by week four. Key secondary endpoints included the overall seroconversion and cellular immune response; safety was assessed at weeks one and four. Seroconversion rates at week four were comparable between vector (6/27 patients, 22%) and mRNA (9/28, 32%) vaccine (p=0.6). Overall, 27% of patients seroconverted; specific T–cell responses were observed in 20/20 (100%) vector versus 13/16 (81%) mRNA vaccinated patients. Newly induced humoral and/or cellular responses occurred in 9/11 (82%) patients. No serious adverse events, related to immunization, were observed. This enhanced humoral and/or cellular immune response supports an additional booster vaccination in non–seroconverted patients irrespective of a heterologous or homologous vaccination regimen.

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“…Recent studies suggest that individuals given ChAdOx1 nCoV-19 as the first dose followed by either the BNT162b2 or mRNA-1273 as the second dose, experience a robust cellular and immune response [ 19 , 20 , 21 , 22 ], which appears to be of at least similar or even greater magnitude compared with individuals given a homologous ChAdOx1 nCoV-19 / ChAdOx1 nCoV-19 schedule [ 20 , 22 , 23 , 24 ]. Yet, there is to our knowledge no data regarding effectiveness of heterologous ChAdOx1 nCoV-19 / mRNA prime-boost vaccination against symptomatic Covid-19 infection.…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of heterologous ChAdOx1 nCoV-19 and mRNA prime-boost vaccination against symptomatic Covid-19 infection in Sweden: A nationwide cohort study

Nordström

Ballin

Nordström

2021

The Lancet Regional Health - Europe

136

118

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Heterologous prime–boost vaccination with ChAdOx1 nCoV-19 and BNT162b2

Cited by 119 publications

References 5 publications

Reactogenicity Correlates Only Weakly with Humoral Immunogenicity after COVID-19 Vaccination with BNT162b2 mRNA (Comirnaty®)

Reactogenicity Correlates Only Weakly with Humoral Immunogenicity after COVID-19 Vaccination with BNT162b2 mRNA (Comirnaty®)

Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomized controlled trial

Effectiveness of heterologous ChAdOx1 nCoV-19 and mRNA prime-boost vaccination against symptomatic Covid-19 infection in Sweden: A nationwide cohort study

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