SARS coronavirus vaccines protect against different coronaviruses

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Abstract

Although SARS-CoV-2 vaccines have shown efficacy against SARS-CoV-2, it is unclear if they can also protect against other coronaviruses that may infect humans in the future. Here, we show that SARS-CoV-2 vaccination in humans elicits cross-reactive antibodies against other coronaviruses. Our studies in mice demonstrate that SARS-CoV-2 vaccination protects against a common cold coronavirus, and that SARS-CoV-1 vaccination protects against SARS-CoV-2. Similarly, infection with a common cold coronavirus also conferred enhanced protection from subsequent infections with other coronaviruses. Mechanistically, both T cells and antibodies mediated cross-protection. This is the first direct demonstration that coronavirus-specific immunity can confer heterologous protection in vivo , providing a rationale for universal coronavirus vaccines.

Highlights

  • SARS-CoV-2 vaccination elicits cross-reactive antibody against other coronaviruses in humans.

  • COVID-19 patients generate cross-reactive antibody against other coronaviruses.

  • A SARS-CoV-1 vaccine protects against SARS-CoV-2.

  • Prior coronavirus infections improve immune protection following heterologous coronavirus challenges.

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    1. SciScore for 10.1101/2021.06.01.446491: (What is this?)

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

      Table 1: Rigor

      EthicsIRB: Human Subjects: All protocols used for subject recruitment, enrollment, blood collection, sample processing and immunological assays with human samples were approved by the Northwestern University Institutional review board (STU00212583).
      Consent: All participants voluntarily enrolled in the study by signing an informed consent form after receiving detailed information of the clinical study.
      IACUC: All mouse experiments with BL2 agents were performed with approval from the Northwestern University Institutional Animal Care and Use Committee (IACUC).
      Sex as a biological variableMice were purchased from Jackson laboratories (approximately half males and half females) and housed at the Northwestern University Center for Comparative Medicine (CCM) or the University of Illinois at Chicago (UIC).
      Randomizationnot detected.
      Blindingnot detected.
      Power Analysisnot detected.
      Cell Line Authenticationnot detected.

      Table 2: Resources

      Antibodies
      SentencesResources
      Protein-specific ELISA (SARS-CoV-2 spike, RBD, nucleocapsid; SARS-CoV- 1 spike; OC43 spike): Antigen-specific total antibody titers were measured by ELISA as described previously (Dangi et al., 2020; Palacio et al., 2020).
      Antigen-specific total
      suggested: (George Fu Gao; Chinese Academy of Sciences; Beijing; China Cat# Z3L1, RRID:AB_2725798)
      Plates were washed three times with wash buffer followed by addition of secondary antibody conjugated to horseradish peroxidase, goat anti-mouse IgG (Southern Biotech) diluted in blocking solution (1:1000) at 100 µl/well were added and incubated for 60 min at room temperature.
      anti-mouse IgG
      suggested: None
      Cells were stained with fluorescently-labelled antibodies against CD44 (IM7 on Pacific Blue), CD8α (53- 6.7 on PerCP-Cy5.5), IFNγ (XMG1.2 on APC).
      CD8α
      suggested: None
      Fluorescently-labelled antibodies were purchased from BD Pharmingen, except for anti-CD44 (which was from Biolegend).
      anti-CD44
      suggested: None
      Experimental Models: Cell Lines
      SentencesResources
      SARS-CoV-2 (MA10) was propagated and tittered on Vero-E6 cells.
      Vero-E6
      suggested: None
      Virus propagation: OC43 was propagated in an 80-90% confluent monolayer of HCT-8 cells (ATCC® CCL-244™) in T175 flasks at a multiplicity of infection (MOI) of 0.01 diluted in 5 mL of RPMI supplemented with 2% FBS, 1% penicillin/streptomycin, and 1% L-glutamine.
      HCT-8
      suggested: None
      SARS-CoV-2 pseudovirus neutralization assays: A SARS-CoV-2 pseudovirus was generated by transfection of HEK-293T cells with a pCAGGS vector expressing the SARS-CoV-2 spike glycoprotein (BEI resources, NIAID, NIH: NR-52310).
      HEK-293T
      suggested: None
      Titers were measured by infecting HEK-293T-hACE2 cells and counting GFP foci under a fluorescence microscope after 24 hr.
      HEK-293T-hACE2
      suggested: RRID:CVCL_A7UK)
      Experimental Models: Organisms/Strains
      SentencesResources
      Mice, vaccinations, infections and challenges: 6-8-week-old C57BL/6, BALB/c, A/J, Ifnar1-/- mice (on a C57BL/6 background) were used.
      C57BL/6
      suggested: None
      BALB/c
      suggested: None
      A/J
      suggested: None
      Ifnar1-/-
      suggested: None
      Recombinant DNA
      SentencesResources
      Vector pCAGGS containing the SARS-related coronavirus 2, Wuhan-Hu-1 spike glycoprotein gene (soluble, stabilized), NR-52394 and receptor binding domain (RBD), NR-52309.
      pCAGGS
      suggested: RRID:Addgene_18926)
      Software and Algorithms
      SentencesResources
      Blood was collected by phlebotomy using BD Vacutainer 10mL tubes containing sodium heparin.
      BD Vacutainer
      suggested: None
      Flow cytometry samples were acquired with a Becton Dickinson Canto II or an LSRII and analyzed using FlowJo (Treestar).
      FlowJo
      suggested: (FlowJo, RRID:SCR_008520)
      TCR analyses were performed using the scRepertoire package30.
      scRepertoire
      suggested: None
      Data were analyzed using Prism (Graphpad).
      Prism
      suggested: (PRISM, RRID:SCR_005375)
      Graphpad
      suggested: (GraphPad, RRID:SCR_000306)

      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:
      A limitation of our study is that we only evaluated heterologous immune protection at an early time post-vaccination or post-infection, and it is possible that cross-protective immunity declines over time. Future studies will determine whether cross-reactive antibodies are produced by plasma cells, or short-lived plasmablasts, which tend to be highly mutated and cross-reactive21, 22. In summary, we show that coronavirus vaccines and coronavirus infections can confer protection against other coronaviruses. These findings provide a framework for the rational design of universal coronavirus vaccines, and present the first definitive demonstration of heterologous immune protection following coronavirus vaccination or infection.

      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.
      • No funding statement was detected.
      • 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.