Evaluating the Neutralizing Ability of a CpG-Adjuvanted S-2P Subunit Vaccine Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants of Concern

  1. Chia-En Lien
  2. Tsun-Yung Kuo
  3. Yi-Jiun Lin
  4. Wei-Cheng Lian
  5. Meei-Yun Lin
  6. Luke Tzu-Chi Liu
  7. Jinyi Cheng
  8. Yu-Chi Chou
  9. Charles Chen

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Abstract

Background

Variants of concern (VoCs) have the potential to diminish the neutralizing capacity of antibodies elicited by vaccines. MVC-COV1901 is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine consisting of recombinant prefusion stabilized spike protein S-2P adjuvanted with CpG 1018 and aluminum hydroxide. We explored the effectiveness of MVC-COV1901 against the VoCs.

Methods

Serum samples were taken from rats and phase 1 clinical trial human subjects immunized with a low, medium, or high dose of MVC-COV1901. The neutralizing titers of serum antibodies were assayed with pseudoviruses coated with the SARS-CoV-2 spike protein of the wild-type (WT), D614G, Alpha, or Beta variants.

Results

Rats vaccinated twice with vaccine containing high doses of antigen retained high levels of neutralization activity against the Beta variant, albeit with a slight reduction compared to WT. After the third dose, neutralizing titers against the Beta variant were noticeably enhanced regardless of the amount of antigen used for immunization. In humans, vaccinated phase 1 subjects still showed appreciable neutralization abilities against the D614G, Alpha, and Beta variants, although neutralizing titers were significantly reduced against the Beta variant.

Conclusions

Two doses of MVC-COV1901 were able to elicit neutralizing antibodies against SARS-CoV-2 variants with an overall tendency of inducing higher immune response at a higher dose level. The neutralizing titers to the Beta variant in rats and humans were lower than those for WT and the Alpha variant. An additional third dose in rats was able to partially compensate for the reduction in neutralization against the Beta variant. We have demonstrated that immunization with MVC-COV1901 was effective against VoCs.

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  1. Version published to 10.1093/cid/ciab711
  2. ScreenIT

    SciScore for 10.1101/2021.03.19.21254000: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: All animal work in the current study was reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) with animal study protocol approval number TFBS2020-010 and CTPS-19-019-01.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Experimental Models: Organisms/Strains
    SentencesResources
    Animal studies: Crl:CD Sprague Dawley (SD) rats were obtained from BioLASCO Taiwan Co. Ltd., and studies were conducted in the Testing Facility for Biological Safety, TFBS Bioscience Inc., and the Center of Toxicology and Preclinical Sciences, QPS Taiwan and immunized as previously described12.
    Crl:CD Sprague Dawley
    suggested: RRID:RGD_734476)
    Pseudovirus neutralization assay: Lentivirus expressing the SARS-CoV-2 spike proteins of the Wuhan-Hu-1 wildtype strain was constructed, and the neutralization assay performed as previously described12.
    Wuhan-Hu-1
    suggested: None
    Software and Algorithms
    SentencesResources
    Animal studies: Crl:CD Sprague Dawley (SD) rats were obtained from BioLASCO Taiwan Co. Ltd., and studies were conducted in the Testing Facility for Biological Safety, TFBS Bioscience Inc., and the Center of Toxicology and Preclinical Sciences, QPS Taiwan and immunized as previously described12.
    BioLASCO
    suggested: None
    Statistical analysis: The analysis package in Prism 6.01 (GraphPad) was used for statistical analysis.
    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:
    Our study’s limitation is that the sera were taken four weeks after the second shot of MVC-COV19 when the immunity has peaked and starting to wane. Therefore, we could not evaluate the impact of waning immunity on the neutralizing capacity against the variants. The study cannot evaluate the role of T-cell responses elicited by the vaccine as it was reported that the T-cell responses to immunization may confer heterotypic coverage and is less affected by variants of concern23. COVID-19 vaccines that conduct phase III clinical trials in South Africa when the B.1.351 strain became predominant showed considerably high protection against severe clinical endpoints, while overall efficacy is lower than sites outside of South Africa24. Since there are no correlates of protection being published for either earlier strains or the emerging variants, it warrants further study on how the reduced neutralizing titers will translate to clinical endpoints.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04487210Active, not recruitingA Study to Evaluate the Safety and Immunogenicity of MVC-COV…

    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.

    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.

  3. Version published to 10.1101/2021.03.19.21254000v1 on medRxiv