Cited by 425SARS-CoV-2 and COVID-19 ResearchImmune responses and vaccinationsVaccine Coverage and Hesitancy

Immune responses against SARS-CoV-2 variants after heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination

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Barros-Martins, Joana, Hammerschmidt, Swantje I., Cossmann, Anne, Odak, Ivan, Stankov, Metodi V., Morillas Ramos, Gema, Dopfer-Jablonka, Alexandra, Heidemann, Annika +17 more·2021·Nature Medicine

Published version of a preprint

Abstract

Currently approved viral vector-based and mRNA-based vaccine approaches against coronavirus disease 2019 (COVID-19) consider only homologous prime-boost vaccination. After reports of thromboembolic events, several European governments recommended using AstraZeneca’s ChAdOx1-nCov-19 (ChAd) only in individuals older than 60 years, leaving millions of already ChAd-primed individuals with the decision to receive either a second shot of ChAd or a heterologous boost with mRNA-based vaccines. However, such combinations have not been tested so far. We used Hannover Medical School’s COVID-19 Contact Study cohort of healthcare professionals to monitor ChAd-primed immune responses before and 3 weeks after booster with ChAd ( n = 32) or BioNTech/Pfizer’s BNT162b2 ( n = 55). Although both vaccines boosted prime-induced immunity, BNT162b2 induced significantly higher frequencies of spike-specific CD4 + and CD8 + T cells and, in particular, high titers of neutralizing antibodies against the B.1.1.7, B.1.351 and P.1 variants of concern of severe acute respiratory syndrome coronavirus 2.

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Research works printed but not linked: 4

  1. Wise, J. Covid-19: European countries suspend use of Oxford-AstraZeneca vaccine after reports of blood clots. BMJ 372, n699 (2021).
  2. Pottegård, A. et al. Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study. BMJ 373, n1114 (2021).
  3. Jablonka, A. et al. Protocol for longitudinal assessment of SARS-CoV- 2-specific immune responses in healthcare professionals in Hannover, Germany: the prospective, longitudinal, observational COVID-19 Contact (CoCo) study. Preprint at https://www.medrxiv.org/content/10.1101/2020.12.0 · DOI
  4. 20242479v1.full (2020). Extended Data Fig. 6 | Neutralizing antibodies interfere with binding of SARS-CoV-2-S-RBD variants to human ACe2. a, Inhibition of interaction of indicated SARS-CoV-2-S-RBD variants with ACE2 by the addition of plasma of a representative vaccinee before (open circles) and after (closed circles) homologous ChAd/ChAd (blue symbols) and heterologous ChAd/BNT (red symbols) booster immunization. Assays were performed in duplicates and are shown as mean percentages of neutralization. Shaded areas represent mean +2 SD of values from pre-COVID-19 plasma. b, Reciprocal titers of neutralizing antibodies against the Wuhan-Spike, B.1.1.7-Spike (Alpha), P.1-Spike (B.1.1.28.1; Gamma), and B.1.351-Spike (Beta) SARS-CoV-2 variants in plasma of each vaccinee before and after the boost immunization. Statistics: Chi-square test for trend. Data are from n = 31 biologically independent sample pairs from the ChAd/ChAd group and n = 54 biologically independent sample pairs from the ChAd/BNT group. For better visualization of identical titer values, data were randomly and proportionally adjusted closely around the precise titer results. · DOI

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Authors
Barros-Martins, J., Hammerschmidt, S. I., Cossmann, A., Odak, I., Stankov, M. V., Morillas Ramos, G., Dopfer-Jablonka, A., Heidemann, A., Ritter, C., Friedrichsen, M., Schultze-Florey, C., Ravens, I., Willenzon, S., Bubke, A., Ristenpart, J., Janssen, A., Ssebyatika, G., Bernhardt, G., Münch, J., Hoffmann, M., Pöhlmann, S., Krey, T., Bošnjak, B., Förster, R., & Behrens, G. M. N.
Affiliations
  • Medizinische Hochschule Hannover (DE)
  • University of Lübeck (DE)
  • Universität Ulm (DE)
  • German Primate Center (DE)
  • German Center for Infection Research (DE)
Corresponding author
  • Bošnjak, Berislav
  • Förster, Reinhold
  • Behrens, Georg M. N.
Venue
Nature Medicine
Published
2021-07-14
Volume
27
Issue
9
Pages
1525-1529
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W3177819637
Cited by
425
References
9
Citations by year
2026: 13 · 2025: 32 · 2024: 28 · 2023: 81 · 2022: 184 · 2021: 87
FWCI
30.06
Type
journal article
Language
en
Open access
Locations
  • Nature Medicine (publishedVersion, cc-by)
  • medRxiv (acceptedVersion)
  • Research Square (acceptedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
  • HZI (Helmholtz Centre for Infection Research) (submittedVersion, cc-by)
Funders
  • Deutsches Zentrum für Infektionsforschung (80018019238, TTU 01.938)
  • Deutsche Forschungsgemeinschaft (ID39087428, 158989968)
  • Niedersächsische Ministerium für Wissenschaft und Kultur (14-76103-184)
  • Bundesministerium für Bildung und Forschung (01KX2021)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
  • Social Sciences › Health › Vaccine Coverage and Hesitancy
Keywords
SARS-CoV-2 variants, heterologous prime-boost, ChAdOx1 nCoV-19 vaccine, BNT162b2, COVID-19 vaccination, booster vaccination, immune response, spike-specific T cells, neutralizing antibodies, Alpha variant, Beta variant, P.1 variant, vaccine safety, thromboembolic events
MeSH terms
Immunogenicity, Vaccine, COVID-19, SARS-CoV-2, COVID-19 Vaccines, BNT162 Vaccine, ChAdOx1 nCoV-19, Antibodies, Viral, Humans, Immunization, Secondary, Vaccination, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, CD4 Lymphocyte Count, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus

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