A novel intranasal administration adenoviral vector-based platform for rapid COVID-19 vaccine development

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Abstract

The coronavirus SARS-CoV-2 has a severe impact on global public health, and the emerging variants threaten the efficacy of the circulating vaccines. Here, we report that a single vaccination with a non-replicating chimpanzee adenovirus-based vaccine against the SARS-CoV-2 Delta variant (JS1-delta) elicits potent humoral, cellular and mucosal immunity in mice. Additionally, a single intranasal administration of JS1-delta provides effective protection against the Delta (B.1.617.2) variant challenge in mice. This study indicates that chimpanzee adenovirus type 3 (ChAd3) derived vector represents a promising platform for antiviral vaccine development against respiratory infections and JS1-delta is worth further investigation in human clinical trials.

Highlights

  • A new chimpanzee adenoviral vaccine against the SARS-CoV-2 Delta variant was developed.

  • The vaccine elicited potent humoral, cellular and mucosal immunity in mice.

  • The vaccine protected mice from the Delta variant challenge.

  • Article activity feed

    1. SciScore for 10.1101/2022.02.21.481247: (What is this?)

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

      Table 1: Rigor

      EthicsIACUC: Animals: The experiments involving animals were approved by and carried out in accordance with the guidelines of the Institutional Experimental Animal Welfare and Ethics Committee.
      Sex as a biological variableSpecific pathogen-free female BALB/c mice were obtained from Charles River Laboratories
      Randomizationnot detected.
      Blindingnot detected.
      Power Analysisnot detected.
      Cell Line Authenticationnot detected.

      Table 2: Resources

      Experimental Models: Cell Lines
      SentencesResources
      In brief, adherent HEK293 cells were transfected with recombinant pCDNA3.1-delta S-His (1-1141) using PEI and incubated in 37°C. 5% CO2 for 72 h.
      HEK293
      suggested: None
      The mixtures were added to pre-plated Vero E6 (ATCC) cell monolayers in 96-well microplate and cultured for 3-4 day.
      Vero E6
      suggested: None
      Experimental Models: Organisms/Strains
      SentencesResources
      Specific pathogen-free female BALB/c mice were obtained from Charles River Laboratories
      BALB/c
      suggested: RRID:IMSR_ORNL:BALB/cRl)
      Specific pathogen-free female H11-K18-hACE2 mice were obtained from GemPharmatech.
      H11-K18-hACE2
      suggested: None
      Recombinant DNA
      SentencesResources
      Construction of JS1-delta: The chemosynthetic JS1 genome was cyclized by the additional pUC57 backbone and was linearized by a double enzyme digestion with I-Ceu □ and PI-Sce □.
      pUC57
      suggested: RRID:Addgene_40306)
      In brief, adherent HEK293 cells were transfected with recombinant pCDNA3.1-delta S-His (1-1141) using PEI and incubated in 37°C. 5% CO2 for 72 h.
      pCDNA3.1-delta S-His
      suggested: None
      Software and Algorithms
      SentencesResources
      Specific pathogen-free female H11-K18-hACE2 mice were obtained from GemPharmatech.
      GemPharmatech
      suggested: (GemPharmatech, RRID:SCR_017239)
      Neutralization assay: To test SARS-CoV-2 PNAbs, serial dilutions of heat-inactivated sera were mixed with B.1.617.2 pseudoviruse (Beijing Tiantan Pharmacy Biological Research & Development Company), incubated for 1 h at 37 °C and added to ACE2-293T (YEASEN) cells in duplicate in 96-well microplate.
      Pharmacy Biological
      suggested: None
      Images were collected under a Pannoramic MIDI system (3DHISTECH, Thermo) using Pannoramic scanner software and analyzed by ImageJ (NIH).
      ImageJ
      suggested: (ImageJ, RRID:SCR_003070)

      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:
      To circumvent these limitations, considerable efforts have been made to develop new adenoviral vectors from lower seroprevalence hAds (such as hAd26, hAd28 and hAd35)18,25,26 or from non-human primate sources (such as ChAdY25 and ChAd63)27,28. ChAd3 is one of the most promising candidates and shows well safety and tolerance in clinical trials targeting hepatitis C virus and Ebola virus.29–32 In this study, we have demonstrated for the first time, to our knowledge, that a ChAd3-derived SARS-CoV-2 vaccine can induce potent humoral and cellular immune responses and completely protect mice from B.1.617.2 challenge. At the same time, another vaccine candidate JS1-beta targeting B. 1.351 shows favorable immunogenicity in mice (Fig. S1), and JS1-omicron targeting B.1.1.529 is also under testing. The longevity of antigen-specific immune responses and the influence of anti-vector immunity induced by the vaccines, along with the cooperation with different boosters, will be further investigated. Recently, mucosal vaccines against SARS-CoV-2 have raised increasing interests due to their important advantage in preventing virus replication in the upper respiratory tracts, which is essential to interrupt pulmonary infection and person to person transmission.33–36 Compared with IM injection, the IN vaccination can elicit not only comparable systemic immunity but also additional pathogen-specific mucosal immunity, resulting in a first line of defense against the virus invasion.34–36 In our st...

      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.