Updated vaccine protects from infection with SARS-CoV-2 variants, prevents transmission and is immunogenic against Omicron in hamsters

  1. Sapna Sharma
  2. Thomas Vercruysse
  3. Lorena Sanchez-Felipe
  4. Winnie Kerstens
  5. Madina Rasulova
  6. Rana Abdelnabi
  7. Caroline S Foo
  8. Viktor Lemmens
  9. Dominique Van Looveren
  10. Piet Maes
  11. Guy Baele
  12. Birgit Weynand
  13. Philippe Lemey
  14. Johan Neyts
  15. Hendrik Jan Thibaut
  16. Kai Dallmeier

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Abstract

Current first-generation COVID-19 vaccines are based on prototypic spike sequences from ancestral 2019 SARS-CoV-2 strains. However, the ongoing pandemic is fueled by variants of concern (VOC) that threaten to escape vaccine-mediated protection. Here we show in a stringent hamster model that immunization using prototypic spike expressed from a potent YF17D viral vector (1) provides vigorous protection against infection with ancestral virus (B lineage) and VOC Alpha (B.1.1.7), however, is insufficient to provide maximum protection against the Beta (B.1.351) variant. To improve vaccine efficacy, we created a revised vaccine candidate that carries an evolved spike antigen. Vaccination of hamsters with this updated vaccine candidate provides full protection against intranasal challenge with all four VOCs Alpha, Beta, Gamma (P.1) and Delta (B.1.617.2) resulting in complete elimination of infectious virus from the lungs and a marked improvement in lung pathology. Vaccinated hamsters did also no longer transmit the Delta variant to non-vaccinated sentinels. Hamsters immunized with our modified vaccine candidate also mounted marked neutralizing antibody responses against the recently emerged Omicron (B.1.1.529) variant, whereas the old vaccine employing prototypic spike failed to induce immunity to this antigenically distant virus. Overall, our data indicate that current first-generation COVID-19 vaccines need to be urgently updated to cover newly emerging VOCs to maintain vaccine efficacy and to impede virus spread at the community level.

Significance Statement

SARS-CoV-2 keeps mutating rapidly, and the ongoing COVID-19 pandemic is fueled by new variants escaping immunity induced by current first-generation vaccines. There is hence an urgent need for universal vaccines that cover variants of concern (VOC). In this paper we show that an adapted version of our vaccine candidate YF-S0* provides full protection from infection, virus transmission and disease by VOCs Alpha, Beta, Gamma and Delta, and also results in markedly increased levels of neutralizing antibodies against recently emerged Omicron VOC in a stringent hamster model. Our findings underline the necessity to update COVID-19 vaccines to curb the pandemic, providing experimental proof on how to maintain vaccine efficacy in view of an evolving SARS-CoV-2 diversity.

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  1. Version published to 10.1101/2021.11.12.468374v3 on bioRxiv
  2. Version published to 10.1101/2021.11.12.468374v2 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.11.12.468374: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Housing and experimental infections of hamsters have been described (Boudewijns et al., 2020; Kaptein et al., 2020; Sanchez-Felipe et al., 2021) and conducted under supervision of the ethical committee of KU Leuven (license P050/2020 and P055/2021).
    Sex as a biological variableIn brief, 6 to 8 weeks old female Syrian hamsters (Mesocricetus auratus) were sourced from Janvier Laboratories and kept per two in individually ventilated isolator cages.
    Randomizationnot detected.
    BlindingHistopathology: For histological examination, the lungs were fixed overnight in 4% formaldehyde, embedded in paraffin and tissue sections (5 μm) after staining with H&E scored blindly for lung damage (cumulative score of 1 to 3 each for congestion, intra-alveolar hemorrhage, apoptotic bodies in bronchial epithelium, necrotizing bronchiolitis, perivascular edema, bronchopneumonia, perivascular inflammation, peribronchial inflammation, and vasculitis) as previously established (Abdelnabi et al., 2021; Boudewijns et al., 2020) Blocking of viral transmission: Hamsters (N=6) were vaccinated with 104 PFU of vaccine once, were bled at day 21 and infected with delta variant with 1×105 TCID50, intranasally.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Two hours later, the medium was replaced by medium containing anti-VSV-G antibody (I1-hybridoma, ATCC CRL-2700) to neutralize residual VSV-G input.
    anti-VSV-G
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Median tissue culture infectious doses (TCID50) were defined by titration as described (Abdelnabi et al., 2021; Boudewijns et al., 2020) using Vero E6 cells as substrate, except for VOC Delta, for which A549 cells were used for a more pronounced virus induced cytopathic effect (CPE).
    Vero E6
    suggested: None
    A549
    suggested: NCI-DTP Cat# A549, RRID:CVCL_0023)
    Briefly, depending on the plasmid background, BHK-21J cells (variant B.1/D614G) or HEK-293T cells (Beta, Gamma and Delta) were transfected with the respective SARS-CoV-2 protein expression plasmids, and one day later infected (MOI = 2) with GFP-encoding VSVΔG backbone virus (Whitt, 2010).
    BHK-21J
    suggested: None
    HEK-293T
    suggested: None
    Software and Algorithms
    SentencesResources
    Gasthuisberg, Leuven) and characterized by direct sequencing using a MinION as described before (Boudewijns et al., 2020)
    MinION
    suggested: (MinION, RRID:SCR_017985)
    Protective nAb levels were calculated using logistic regression analysis in GraphPad Prism (version 9) as described (van der Lubbe et al., 2021) Similarly, hamsters were vaccinated twice with 104 YF-S0* (N=24) or sham (N=16) at day 0 and day 7.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Statistical analysis: All statistical analyses were performed using GraphPad Prism 9 software (GraphPad, San Diego, CA, USA).
    GraphPad
    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.

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  4. Version published to 10.1101/2021.11.12.468374v1 on bioRxiv