Diminished neutralization responses towards SARS-CoV-2 Omicron VoC after mRNA or vector-based COVID-19 vaccinations

  1. Henning Jacobsen
  2. Monika Strengert
  3. Henrike Maaß
  4. Mario Alberto Ynga Durand
  5. Maeva Katzmarzyk
  6. Barbora Kessel
  7. Manuela Harries
  8. Ulfert Rand
  9. Leila Abassi
  10. Yeonsu Kim
  11. Tatjana Lüddecke
  12. Kristin Metzdorf
  13. Pilar Hernandez
  14. Julia Ortmann
  15. Jana-Kristin Heise
  16. Stefanie Castell
  17. Daniela Gornyk
  18. Stephan Glöckner
  19. Vanessa Melhorn
  20. Yvonne Kemmling
  21. Berit Lange
  22. Alex Dulovic
  23. Patrick Marsall
  24. Julia Häring
  25. Daniel Junker
  26. Nicole Schneiderhan-Marra
  27. Markus Hoffmann
  28. Stefan Pöhlmann
  29. Gérard Krause
  30. Luka Cicin-Sain

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Abstract

SARS-CoV-2 variants accumulating immune escape mutations provide a significant risk to vaccine-induced protection against infection. The novel variant of concern (VoC) Omicron BA.1 and its sub-lineages have the largest number of amino acid alterations in its Spike protein to date. Thus, they may efficiently escape recognition by neutralizing antibodies, allowing breakthrough infections in convalescent and vaccinated individuals in particular in those who have only received a primary immunization scheme. We analyzed neutralization activity of sera from individuals after vaccination with all mRNA-, vector- or heterologous immunization schemes currently available in Europe by in vitro neutralization assay at peak response towards SARS-CoV-2 B.1, Omicron sub-lineages BA.1, BA.2, BA.2.12.1, BA.3, BA.4/5, Beta and Delta pseudotypes and also provide longitudinal follow-up data from BNT162b2 vaccinees. All vaccines apart from Ad26.CoV2.S showed high levels of responder rates (96–100%) towards the SARS-CoV-2 B.1 isolate, and minor to moderate reductions in neutralizing Beta and Delta VoC pseudotypes. The novel Omicron variant and its sub-lineages had the biggest impact, both in terms of response rates and neutralization titers. Only mRNA-1273 showed a 100% response rate to Omicron BA.1 and induced the highest level of neutralizing antibody titers, followed by heterologous prime-boost approaches. Homologous BNT162b2 vaccination, vector-based AZD1222 and Ad26.CoV2.S performed less well with peak responder rates of 48%, 56% and 9%, respectively. However, Omicron responder rates in BNT162b2 recipients were maintained in our six month longitudinal follow-up indicating that individuals with cross-protection against Omicron maintain it over time. Overall, our data strongly argue for booster doses in individuals who were previously vaccinated with BNT162b2, or a vector-based primary immunization scheme.

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  1. Version published to 10.1038/s41598-022-22552-y
  2. Version published to 10.1101/2021.12.21.21267898v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.12.21.21267898: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: The study was approved by the Ethics Committee of the Hannover Medical School (9086_BO_S_2020) and was in line with the Declaration of Helsinki.
    Sex as a biological variablenot detected.
    RandomizationRecruitment of eligible participants (>18 years) was based on age- and sex-stratified random sampling with information provided by the respective local residents’ registration offices
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line AuthenticationContamination: All cell lines used within this study were below a passage of 50 and were regularly checked for mycoplasma contamination.

    Table 2: Resources

    Antibodies
    SentencesResources
    Cells were washed once with PBS and medium containing anti-VSV-G antibody (culture supernatant from L1-hybridoma cells) was added to neutralize residual input virus.
    anti-VSV-G
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Transfection of 293T cells was performed using calcium-phosphate.
    293T
    suggested: KCB Cat# KCB 200744YJ, RRID:CVCL_0063)
    After incubation, the sample-virus mixture was transferred to VeroE6 cells at 100% confluence which were seeded the day before.
    VeroE6
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Recombinant DNA
    SentencesResources
    In brief, 293T cells were transfected with pCG1 plasmids expressing different SARS-CoV-2 Spike proteins, using calcium-phosphate. 24 h post transfection, cells were infected with a replication-deficient reporter VSV-G (VSV*ΔG-Fluc) at an MOI of 3 for 1 h at 37 °C [20].
    pCG1
    suggested: None
    Software and Algorithms
    SentencesResources
    Automated segmentation and fluorescent foci counting was performed using the IncuCyte GUI software (versions 2019B Rev1 and 2021B) Raw data were plotted in GraphPad prism (v8) and FRNT50 was calculated with a variable slope, four parameter regression analysis.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Data analysis and statistics: Initial results collation and matching to metadata was done in Excel 2016 and R 4.1.0.
    Excel
    suggested: None
    Graphs and statistical calculations were performed using GraphPad Prism version 9.0.2 for Windows (GraphPad Software).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2021.12.21.21267898v1 on medRxiv