Distinct neutralizing kinetics and magnitudes elicited by different SARS-CoV-2 variant spikes

  1. Yang Liu
  2. Jianying Liu
  3. Jing Zou
  4. Ping Ren
  5. Scott C. Weaver
  6. Xuping Xie
  7. Pei-Yong Shi

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

The rapid evolution of SARS-CoV-2 mandates a better understanding of cross-protection between variants after vaccination or infection, but studies directly evaluating such cross-protection are lacking. Here we report that immunization with different variant spikes elicits distinct neutralizing kinetics and magnitudes against other SARS-CoV-2 variants. After immunizing hamsters with wild-type or mutant SARS-CoV-2 bearing variant spikes from Alpha, Beta, Gamma, or Epsilon, the animals developed faster and greater neutralization activities against homologous SARS-CoV-2 variants than heterologous variants, including Delta. The rank of neutralizing titers against different heterologous variants varied, depending on the immunized variant spikes. The differences in neutralizing titers between homologous and heterologous variants were as large as 62-, 15-, and 9.7-fold at days 14, 28, and 45 post-immunization, respectively. Nevertheless, all immunized hamsters were protected from challenges with all SARS-CoV-2 variants, including those exhibiting the lowest neutralizing antibody titers. The results provide insights into the COVID-19 vaccine booster strategies.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2021.09.02.458740: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: The protocol was approved by the Institutional Animal Care and Use Committee (IACUC) at UTMB.
    IRB: Human serum specimens: The research protocol regarding the use of human serum specimens was reviewed and approved by the University of Texas Medical Branch (UTMB) Institutional Review Board.
    Sex as a biological variableHamster infections: Four- to six-week-old male golden Syrian hamsters, strain HsdHan:AURA (Envigo, Indianapolis, IN), were intranasally immunized with 106 PFU recombinant WT or variant spike virus on day 0.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line AuthenticationAuthentication: The authenticity of Vero E6 cells was verified using Short Tandem Repeat profiling by ATCC.
    Contamination: The cells were tested negative for mycoplasma.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    The virus was serially diluted in DMEM with 2% FBS and 200 μl diluted viruses were transferred onto the monolayer of Vero E6 cells.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    The curves of the relative infectivity versus the serum dilutions (log10 values) were plotted using Prism 9 (GraphPad).
    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: We detected the following sentences addressing limitations in the study:
    A limitation of this study is the use of chimeric viruses rather than the use of clinically approved vaccine platforms for expressing variant spikes or clinical variant isolates for the challenge. The neutralizing profile elicited by chimeric viruses may differ from that elicited by the clinically approved vaccine platforms. In chimeric virus-immunized hamsters, immune responses to non-spike viral proteins may provide added protection when compared with animals immunized with spike-alone vaccines such as mRNA and adenovirus-expression platforms. Despite this limitation, it is conceivable that the relative rank of neutralizing levels would be preserved against different SARS-CoV-2 variants. In summary, increasing global immunization with the currently available safe and effective vaccines, together with boosters when needed, is the strategy to end the COVID-19 pandemic. The design of the booster vaccines depends on whether the newly emerged variants can escape the immunity generated by the current vaccines or natural infections. Potential immune escape of any new variants should be closely monitored by laboratory studies and real-world breakthroughs in vaccinated and infected individuals.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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.

  2. Version published to 10.1101/2021.09.02.458740v1 on bioRxiv