Vaccination with B.1.1.7, B.1.351 and P.1 variants protects mice from challenge with wild type SARS-CoV-2

  1. Fatima Amanat
  2. Shirin Strohmeier
  3. Philip Meade
  4. Nicholas Dambrauskas
  5. Barbara Mühlemann
  6. Derek J. Smith
  7. Vladimir Vigdorovich
  8. D. Noah Sather
  9. Lynda Coughlan
  10. Florian Krammer

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Abstract

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been highly efficient in protecting against coronavirus disease 2019 (COVID-19). However, the emergence of viral variants that are more transmissible and, in some cases, escape from neutralizing antibody responses has raised concerns. Here, we evaluated recombinant protein spike antigens derived from wild type SARS-CoV-2 and from variants B.1.1.7, B.1.351 and P.1 for their immunogenicity and protective effect in vivo against challenge with wild type SARS-CoV-2 in the mouse model. All proteins induced high neutralizing antibodies against the respective viruses but also induced high cross-neutralizing antibody responses. The decline in neutralizing titers between variants was moderate, with B.1.1.7 vaccinated animals having a maximum fold reduction of 4.8 against B.1.351 virus. P.1 induced the most cross-reactive antibody responses but was also the least immunogenic in terms of homologous neutralization titers. However, all antigens protected from challenge with wild type SARS-CoV-2 in a mouse model.

Author Summary

The emergence of variants of SARS-CoV-2 has led to an urgency to study whether vaccines will lead to cross-protection against these variants. Here, we demonstrate that vaccination with spike proteins of various variants leads to cross-neutralizing responses, as well as protection in a mouse model against wild type SARS-CoV-2.

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  1. ScreenIT

    SciScore for 10.1101/2021.08.05.455212: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: In vivo mouse studies: All animal procedures were performed by adhering to the Institutional Animal Care and Use Committee (IACUC) guidelines.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The next day, cells were stained using a rabbit anti-N antibody (Invitrogen; PA5-81794) as primary and a goat anti-rabbit secondary conjugated to horseradish peroxidase (Invitrogen; 31460).
    anti-N
    suggested: None
    anti-rabbit
    suggested: (Thermo Fisher Scientific Cat# 31460, RRID:AB_228341)
    Experimental Models: Cell Lines
    SentencesResources
    The spike trimer was expressed by transient transfection in 293F cells and purified by affinity chromatography as previously described (PMID: 33842901).
    293F
    suggested: None
    Neutralization assay: Twenty-thousand Vero.E6 cells were seeded per well in a 96-well cell culture plate (Corning; 3340) 1 day prior to performing the assay.
    Vero.E6
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Experimental Models: Organisms/Strains
    SentencesResources
    Six to eight weeks old female, BALB/c mice were vaccinated via the intramuscular route with 3 μg of each respective protein with 1:1 mixture of Addavax (Invivogen) in a total volume of 50 μL.
    BALB/c
    suggested: None
    Recombinant DNA
    SentencesResources
    The spike gene of each respective variant (EPI_ISL_703454, EPI_ISL_745160) was cloned into the pCAGGS vector and used to transfect cells.
    pCAGGS
    suggested: RRID:Addgene_18926)
    EPI_ISL_792680 was cloned into pcDNA3.4 for transient transfection.
    pcDNA3.4
    suggested: RRID:Addgene_131198)
    Software and Algorithms
    SentencesResources
    Data were analyzed in GraphPad Prism 7.
    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: We detected the following sentences addressing limitations in the study:
    Another caveat of our study is that we were not able to include B.1.617.2, B.1.617.1 and C.37 in our analysis even though these are currently important variants. In summary, we found that neutralizing titers are always highest against the homologous virus but that antigenic relationships are not necessarily symmetric and that some variant spike proteins induced more balanced responses (e.g. P.1) than others (B.1.351, B.1.1.7). In addition, the drop in binding antibody is much lower than the drop in neutralizing activity. Non-neutralizing binding antibodies have been shown to play an important role in protection for other diseases caused by virus infections including Ebola virus disease and influenza A and B virus [30–33]. The maintenance of binding antibody and T cell responses against variants could partially explain the maintenance of vaccine efficacy, despite the occasional steep drops in neutralizing antibody titers.

    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

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  2. Version published to 10.1101/2021.08.05.455212v1 on bioRxiv