CoVac501, a self-adjuvanting peptide vaccine conjugated with TLR7 agonists, against SARS-CoV-2 induces protective immunity

  1. Yiru Long
  2. Jianhua Sun
  3. Tian-Zhang Song
  4. Tingting Liu
  5. Feng Tang
  6. Xinxin Zhang
  7. Longfei Ding
  8. Yunqiu Miao
  9. Weiliang Zhu
  10. Xiaoyan Pan
  11. Qi An
  12. Mian Qin
  13. Xiankun Tong
  14. Xionghua Peng
  15. Pan Yu
  16. Peng Zhu
  17. Jianqing Xu
  18. Xiaoyan Zhang
  19. Yachun Zhang
  20. Datao Liu
  21. Ben Chen
  22. Huilin Chen
  23. Leike Zhang
  24. Gengfu Xiao
  25. Jianping Zuo
  26. Wei Tang
  27. Ji Zhou
  28. Heng Li
  29. Zhijian Xu
  30. Hong-Yi Zheng
  31. Xin-Yan Long
  32. Qiuping Qin
  33. Yong Gan
  34. Jin Ren
  35. Wei Huang
  36. Yong-Tang Zheng
  37. Guangyi Jin
  38. Likun Gong

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Abstract

Safe, effective, and economical vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to achieve adequate herd immunity and end the pandemic. We constructed a novel SARS-CoV-2 vaccine, CoVac501, which is a self-adjuvanting peptide vaccine conjugated with Toll-like receptor 7 (TLR7) agonists. The vaccine contains immunodominant peptides screened from the receptor-binding domain (RBD) and is fully chemically synthesized. It has been formulated in an optimized nanoemulsion formulation and is stable at 40 °C for 1 month. In non-human primates (NHPs), CoVac501 elicited high and persistent titers of protective neutralizing antibodies against multiple RBD mutations, SARS-CoV-2 original strain, and variants (B.1.1.7 and B.1.617.2). Specific peptides booster immunization against the B.1.351 variant has also been shown to be effective in improving protection against B.1.351. Meanwhile, CoVac501 elicited the increase of memory T cells, antigen-specific CD8 + T-cell responses, and Th1-biased CD4 + T-cell immune responses in NHPs. Notably, at an extremely high SARS-CoV-2 challenge dose of 1 × 10 7 TCID 50 , CoVac501 provided near-complete protection for the upper and lower respiratory tracts of cynomolgus macaques.

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  1. Version published to 10.1038/s41421-021-00370-2
  2. ScreenIT

    SciScore for 10.1101/2021.04.10.439275: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    S1 to S8 References Materials and Methods:
    Methods
    suggested: None

    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 present study has some limitations that will be addressed in further research. First, the specific role and mechanism of action of TLR7 agonist SZU-101 in the immune effect of CoVac501 remains to be investigated, especially how TLR7 agonists promote antibody affinity maturation and immune memory formation in humoral immunity in vivo. Second, the components and involving mechanism related to lymph node aggregation and better in vivo immune effect of the peptide vaccine caused by F2 nanoemulsion rather than AS03 nanoemulsion also remains to be elucidated. In conclusion, we have developed a novel SARS-CoV-2 vaccine CoVac501, which is a self-adjuvanting peptide vaccine conjugated with TLR7 agonists. CoVac501 is a fully chemically synthesized vaccine with outstanding thermal stability and optimized nanoemulsion formulation. CoVac501 can induce high level, protective and long-lasting neutralizing humoral immune responses and Th1-biased T-cell immune responses in NHPs. Besides, CoVac501 was resistant to multiple mutations of amino acid residues in RBDs. CoVac501 holds great potential for further clinical development and application.

    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: Please consider improving the rainbow (“jet”) colormap(s) used on page 15. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    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 10.1101/2021.04.10.439275v1 on bioRxiv