CpG-adjuvanted stable prefusion SARS-CoV-2 spike protein protected hamsters from SARS-CoV-2 challenge
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Abstract
The COVID-19 pandemic presents an unprecedented challenge to global public health. Rapid development and deployment of safe and effective vaccines are imperative to control the pandemic. In the current study, we applied our adjuvanted stable prefusion SARS-CoV-2 spike (S-2P)-based vaccine, MVC-COV1901, to hamster models to demonstrate immunogenicity and protection from virus challenge. Golden Syrian hamsters immunized intramuscularly with two injections of 1 µg or 5 µg of S-2P adjuvanted with CpG 1018 and aluminum hydroxide (alum) were challenged intranasally with SARS-CoV-2. Prior to virus challenge, the vaccine induced high levels of neutralizing antibodies with 10,000-fold higher IgG level and an average of 50-fold higher pseudovirus neutralizing titers in either dose groups than vehicle or adjuvant control groups. Six days after infection, vaccinated hamsters did not display any weight loss associated with infection and had significantly reduced lung pathology and most importantly, lung viral load levels were reduced to lower than detection limit compared to unvaccinated animals. Vaccination with either 1 μg or 5 μg of adjuvanted S-2P produced comparable immunogenicity and protection from infection. This study builds upon our previous results to support the clinical development of MVC-COV1901 as a safe, highly immunogenic, and protective COVID-19 vaccine.
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SciScore for 10.1101/2021.01.07.425674: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: 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). Randomization Immunization and challenge of hamsters: The hamsters were randomized from different litters into four groups (n=10 for each group): hamsters were vaccinated intramuscularly with 2 injections of vehicle control (PBS), 1 or 5 µg of S-2P protein adjuvanted with 150 µg CpG 1018 and 75 µg aluminum hydroxide (alum), or adjuvant alone at 3 weeks apart. Blinding not detected. Power Analysis not detected. Sex as a biological variable …SciScore for 10.1101/2021.01.07.425674: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: 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). Randomization Immunization and challenge of hamsters: The hamsters were randomized from different litters into four groups (n=10 for each group): hamsters were vaccinated intramuscularly with 2 injections of vehicle control (PBS), 1 or 5 µg of S-2P protein adjuvanted with 150 µg CpG 1018 and 75 µg aluminum hydroxide (alum), or adjuvant alone at 3 weeks apart. Blinding not detected. Power Analysis not detected. Sex as a biological variable Animals and ethical statements: Female golden Syrian hamsters aged 6-9 weeks old on study initiation were obtained from the National Laboratory Animal Center (Taipei, Taiwan). Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Briefly, HEK293-hACE2 cells were seeded in 96-well white isoplates and incubated overnight. HEK293-hACE2suggested: NoneBriefly, 10-fold serial dilutions of each sample were added onto Vero E6 cell monolayer in quadruplicate and incubated for 4 days. Vero E6suggested: RRID:CVCL_XD71)Software and Algorithms Sentences Resources Statistical analysis: The analysis package in Prism 6.01 (GraphPad) was used for statistical analysis. GraphPadsuggested: (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:There are a few limitations of this study. Firstly, the hamsters were challenged with SARS-CoV-2 at 29 days after the second immunization, a relatively short time that did not allow for the evaluation of the durability of protective antibodies. Secondly, none of the animals died in the pre-test or challenge study within the observation time. Thus, the model is not suitable for the evaluation of severe disease or mortality prevention but, rather, is appropriate for evaluation of the effects of immunization on viral challenge-induced moderate disease. Thirdly, nasal swab was not conducted, thus the study did not evaluate the vaccine’s ability to block viral entry or prevent upper respiratory tract infection. Further studies are needed to evaluate the durability of the protective antibody, the capacity of MVC-COV1901 to prevent severe disease, mortality, or viral entry.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04695652 Recruiting A Study to Evaluate MVC-COV1901 Vaccine Against COVID-19 in … 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.
- No funding statement was detected.
- No protocol registration statement was detected.
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