Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 342

The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.

Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study

Open access
Hillus, David, Schwarz, Tatjana, Tober-Lau, Pinkus, Vanshylla, Kanika, Hastor, Hana, Thibeault, Charlotte, Jentzsch, Stefanie, Helbig, Elisa T, Lippert, Lena J, Tscheak, Patricia, Schmidt, Marie Luisa, Riege, Johanna, Solarek, André, von Kalle, Christof, Dang-Heine, Chantip, Gruell, Henning, Kopankiewicz, Piotr, Suttorp, Norbert, Drosten, Christian, Bias, Harald, Seybold, Joachim, Al-Rim, Ben, Bardtke, Lara, Beheim-Schwarzbach, Jörn Ilmo, Behn, Kerstin, Bergfeld, Leon, Bethke, Norma, Bleicker, Tobias, Briesemeister, Dana, Brumhard, Sophia, Conrad, Claudia, Dieckmann, Sebastian, Frey, Doris, Gabelich, Julie-Anne, Georg, Philipp, Gläser, Ute, Hasler, Lisbeth, Hetey, Andreas, Hiller, Anna Luisa, Horn, Alexandra, Hülso, Claudia, Kegel, Luisa, Koch, Willi, Krannich, Alexander, Kroneberg, Paolo, Lisy, Michelle, Mackeldanz, Petra, Maeß, Birgit, Münn, Friederike, Olk, Nadine, Peiser, Christian, Pohl, Kai, Hermel, Annelie, Rönnefarth, Maria, Rubisch, Carolin, Sanchez Rezza, Angela, Schellenberger, Isabelle, Schenkel, Viktoria, Schlesinger, Jenny, Schmidt, Sein, Schwanitz, Georg, Sinnigen, Anne-Sophie, Stubbemann, Paula, Tesch, Julia, Treue, Denise, Wendisch, Daniel, Zvorc, Saskia, Klein, Florian, Kurth, Florian, Corman, Victor Max, Sander, Leif Erik·2021·The Lancet Respiratory Medicine
DOI 10.1016/s2213-2600(21)00357-x

Published version of a preprint

Open this paper in CoChat — free account

Abstract

Background Heterologous vaccine regimens have been widely discussed as a way to mitigate intermittent supply shortages and to improve immunogenicity and safety of COVID-19 vaccines. We aimed to assess the reactogenicity and immunogenicity of heterologous immunisations with ChAdOx1 nCov-19 (AstraZeneca, Cambridge, UK) and BNT162b2 (Pfizer-BioNtech, Mainz, Germany) compared with homologous BNT162b2 and ChAdOx1 nCov-19 immunisation. Methods This is an interim analysis of a prospective observational cohort study enrolling health-care workers in Berlin (Germany) who received either homologous ChAdOx1 nCov-19 or heterologous ChAdOx1 nCov-19–BNT162b2 vaccination with a 10–12-week vaccine interval or homologous BNT162b2 vaccination with a 3-week vaccine interval. We assessed reactogenicity after the first and second vaccination by use of electronic questionnaires on days 1, 3, 5, and 7. Immunogenicity was measured by the presence of SARS-CoV-2-specific antibodies (full spike-IgG, S1-IgG, and RBD-IgG), by an RBD–ACE2 binding inhibition assay (surrogate SARS-CoV-2 virus neutralisation test), a pseudovirus neutralisation assay against two variants of concerns (alpha [B.1.1.7] and beta [B.1.351]), and anti-S1-IgG avidity. T-cell reactivity was measured by IFN-γ release assay. Findings Between Dec 27, 2020, and June 14, 2021, 380 participants were enrolled in the study, with 174 receiving homologous BNT162b2 vaccination, 38 receiving homologous ChAdOx1 nCov-19 vaccination, and 104 receiving ChAdOx1 nCov-19–BNT162b2 vaccination. Systemic symptoms were reported by 103 (65%, 95% CI 57·1–71·8) of 159 recipients of homologous BNT162b2, 14 (39%, 24·8–55·1) of 36 recipients of homologous ChAdOx1 nCov-19, and 51 (49%, 39·6–58·5) of 104 recipients of ChAdOx1 nCov-19–BNT162b2 after the booster immunisation. Median anti-RBD IgG levels 3 weeks after boost immunisation were 5·4 signal to cutoff ratio (S/co; IQR 4·8–5·9) in recipients of homologous BNT162b2, 4·9 S/co (4·3–5·6) in recipients of homologous ChAdOx1 nCov-19, and 5·6 S/co (5·1–6·1) in recipients of ChAdOx1 nCov-19– BNT162b2. Geometric mean of 50% inhibitory dose against alpha and beta variants were highest in recipients of ChAdOx1 nCov-19–BNT162b2 (956·6, 95% CI 835·6–1095, against alpha and 417·1, 349·3–498·2, against beta) compared with those in recipients of homologous ChAdOx1 nCov-19 (212·5, 131·2–344·4, against alpha and 48·5, 28·4–82·8, against beta; both p<0·0001) or homologous BNT162b2 (369·2, 310·7–438·6, against alpha and 72·4, 60·5–86·5, against beta; both p<0·0001). SARS-CoV-2 S1 T-cell reactivity 3 weeks after boost immunisation was highest in recipients of ChAdOx1 nCov-19–BNT162b2 (median IFN-γ concentration 4762 mIU/mL, IQR 2723–8403) compared with that in recipients of homologous ChAdOx1 nCov-19 (1061 mIU/mL, 599–2274, p<0·0001) and homologous BNT162b2 (2026 mIU/mL, 1459–4621, p=0·0008) vaccination. Interpretation The heterologous ChAdOx1 nCov-19–BNT162b2 immunisation with 10–12-week interval, recommended in Germany, is well tolerated and improves immunogenicity compared with homologous ChAdOx1 nCov-19 vaccination with 10–12-week interval and BNT162b2 vaccination with 3-week interval. Heterologous prime-boost immunisation strategies for COVID-19 might be generally applicable. Funding Forschungsnetzwerk der Universitätsmedizin zu COVID-19, the German Ministry of Education and Research, Zalando SE.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/s2213-2600(21)00357-x

Cites

11 of 11 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 11 references

Research works printed but not linked: 11

  1. Committee, 2021, Signal assessment report on embolic and thrombotic events (SMQ) with COVID-19 vaccine (ChAdOx1-S [recombinant])—COVID-19 vaccine AstraZeneca (other viral vaccines), EPITT, 24
  2. Schultz, 2021, Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination, N Engl J Med, 384, 2124, 10.1056/NEJMoa2104882 · DOI · Paper page
  3. Ledford, 2021, Could mixing COVID vaccines boost immune response?, Nature, 590, 375, 10.1038/d41586-021-00315-5 · doi:10.1038/d41586-021-00315-5
  4. Shaw, 2021, Heterologous prime-boost COVID-19 vaccination: initial reactogenicity data, Lancet, 397, 2043, 10.1016/S0140-6736(21)01115-6 · DOI · Paper page
  5. Mahase, 2021, COVID-19: one dose of vaccine cuts risk of passing on infection by as much as 50%, research shows, BMJ, 373
  6. Pollard, 2021, Safety and immunogenicity of a two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Europe (EBOVAC2): a randomised, observer-blind, participant-blind, placebo-controlled, phase 2 trial, Lancet Infect Dis, 21, 493, 10.1016/S1473-3099(20)30476-X · DOI
  7. Borobia, 2021, Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicentre, open-label, randomised, controlled, phase 2 trial, Lancet, 398, 121, 10.1016/S0140-6736(21)01420-3 · DOI · Paper page
  8. Schwarz, 2021, Delayed antibody and T-cell response to BNT162b2 vaccination in the elderly, Germany, Emerg Infect Dis, 27, 2174, 10.3201/eid2708.211145 · DOI
  9. Brown, 2001, Interval estimation for a binomial proportion, Stat Sci, 16, 101, 10.1214/ss/1009213286 · DOI · Paper page
  10. Walsh, 2020, Safety and immunogenicity of two RNA-based COVID-19 vaccine candidates, N Engl J Med, 383, 2439, 10.1056/NEJMoa2027906 · doi:10.1056/nejmoa2027906 · Paper page
  11. Folegatti, 2020, Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial, Lancet, 396, 467, 10.1016/S0140-6736(20)31604-4 · DOI · Paper page

Cited by

Metadata

Authors
Hillus, D., Schwarz, T., Tober-Lau, P., Vanshylla, K., Hastor, H., Thibeault, C., Jentzsch, S., Helbig, E. T., Lippert, L. J., Tscheak, P., Schmidt, M. L., Riege, J., Solarek, A., von Kalle, C., Dang-Heine, C., Gruell, H., Kopankiewicz, P., Suttorp, N., Drosten, C., Bias, H., Seybold, J., Al-Rim, B., Bardtke, L., Beheim-Schwarzbach, J. I., Behn, K., Bergfeld, L., Bethke, N., Bleicker, T., Briesemeister, D., Brumhard, S., Conrad, C., Dieckmann, S., Frey, D., Gabelich, J.-A., Georg, P., Gläser, U., Hasler, L., Hetey, A., Hiller, A. L., Horn, A., Hülso, C., Kegel, L., Koch, W., Krannich, A., Kroneberg, P., Lisy, M., Mackeldanz, P., Maeß, B., Münn, F., Olk, N., Peiser, C., Pohl, K., Hermel, A., Rönnefarth, M., Rubisch, C., Sanchez Rezza, A., Schellenberger, I., Schenkel, V., Schlesinger, J., Schmidt, S., Schwanitz, G., Sinnigen, A.-S., Stubbemann, P., Tesch, J., Treue, D., Wendisch, D., Zvorc, S., Klein, F., Kurth, F., Corman, V. M., & Sander, L. E.
Venue
The Lancet Respiratory Medicine
Publisher
Elsevier BV
Published
2021-11
Volume
9
Issue
11
Pages
1255-1265
ISSN
2213-2600 (ISSN-L)
DOI
10.1016/s2213-2600(21)00357-x
OpenAlex
W3192494915
Cited by
342
References
11
FWCI
23.25
Type
journal article
Language
en
Open access
bronze
Licence
Funders
Federal Ministry of Education and Research Berlin Office

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.