Protection of hamsters challenged with SARS-CoV-2 after two doses of MVC-COV1901 vaccine followed by a single intranasal booster with nanoemulsion adjuvanted S-2P vaccine

  1. Yi-Jiun Lin
  2. Meei-Yun Lin
  3. Ya-Shan Chuang
  4. Luke Tzu-Chi Liu
  5. Tsun-Yung Kuo
  6. Charles Chen
  7. Shyamala Ganesan
  8. Ali Fattom
  9. Vira Bitko
  10. Chia-En Lien

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Abstract

Intramuscular vaccines have greatly reduced hospitalization and death due to severe COVID-19. However, most countries are experiencing a resurgence of infection driven predominantly by the Delta and Omicron variants of SARS-CoV-2. In response, booster dosing of COVID-19 vaccines has been implemented in many countries to address waning immunity and reduced protection against the variants. However, intramuscular boosting fails to elicit mucosal immunity and therefore does not solve the problem of persistent viral carriage and transmission, even in patients protected from severe disease. In this study, two doses of stabilized prefusion SARS-CoV-2 spike (S-2P)-based intramuscular vaccine adjuvanted with Alum/CpG1018, MVC-COV1901, were used as a primary vaccination series, followed by an intranasal booster vaccination with nanoemulsion (NE01)-adjuvanted S-2P vaccine in a hamster model to demonstrate immunogenicity and protection from viral challenge. Here we report that this vaccination regimen resulted not only in the induction of robust immunity and protection against weight loss and lung pathology following challenge with SARS-CoV-2, but also led to increased viral clearance from both upper and lower respiratory tracts. Our findings showed that intramuscular MVC-COV1901 vaccine followed by a booster with intranasal NE01-adjuvanted vaccine promotes protective immunity against both viral infection and disease, suggesting that this immunization protocol may offer a solution in addressing a significant, unmet medical need for both the COVID-19 and future pandemics.

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  1. Version published to 10.1038/s41598-022-15238-y
  2. ScreenIT

    SciScore for 10.1101/2022.02.24.481901: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: 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 TFBS2020-019 and Academia Sinica (approval number: 20-10-1526).
    Sex as a biological variableAnimals and ethical statements: Female golden Syrian hamsters aged 8-10 weeks at study initiation were obtained from the National Laboratory Animal Center (Taipei,
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    P protein antigen: Recombinant stabilized trimeric full length S protein expressed by stable CHO cell line was provided by Medigen Vaccine Biologics Corporation as described previously28, 31.
    CHO
    suggested: None
    The samples were incubated at 37°C for 1 hour before addition to plated HEK293-hACE2 cells.
    HEK293-hACE2
    suggested: None
    In brief, lungs were homogenized, clarified by centrifugation and supernatant was diluted 10-fold and plated onto Vero cells in quadruplicate for live virus estimation.
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    Software and Algorithms
    SentencesResources
    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:
    Admittedly, the current study has limitations. Specifically, we did not measure the levels of IgA as an indicator of mucosal immunity in the nasal, or lung tissues, and we did not investigate the homing of T- and B-cells to mucosal tissues. We also did not test whether using IN as a primary series of vaccination (as in the previously referred IN ChAdOx1 nCoV-19 study) can induce the same level of immunity and protection as seen when using IN as a booster. Detection of subgenomic RNA should be done in the future studies to better corroborate the TCID50 live virus count with viral RNA titer as genomic RNA can detect RNA from both live and dead virus, as well as viral RNAs released from dead cells, whereas subgenomic RNAs are only found in actively replicating cells but not packaged in virions39. The original Wuhan and other variants of SARS-CoV-2 have been replaced by the circulating Omicron and Delta variants9 and most likely the virus will continue to evolve and produce new VoCs. The outcomes of IN vaccination with MVC-COV1901 adjuvanted with NE01 against VoCs was not investigated in this study. However, our previous data have shown that administration of booster dose of MVC-COV1901 of either wildtype S-2P or Beta variant of S-2P could confer protection against Delta variant challenge in hamsters40. In addition, three doses of MVC-COV1901 also improved immunogenicity against VoCs compared to two doses of MVC-COV1901 in a clinical trial41. Therefore, it is reasonable to assume...

    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

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  3. Version published to 10.1101/2022.02.24.481901v1 on bioRxiv