Development and pre-clinical evaluation of Newcastle disease virus-vectored SARS-CoV-2 intranasal vaccine candidate
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Abstract
The COVID-19 pandemic has claimed the lives of millions of people worldwide and threatens to become an endemic problem, therefore the need for as many types of vaccines as possible is of high importance.
Because of the millions of doses required, it is desirable that vaccines are not only safe and effective, but also easy to administer, store, and inexpensive to produce.
Newcastle Disease Virus (NDV) is responsible for a respiratory disease in chickens. It has no pathogenic homologue in humans. NDV is recognized as an oncolytic virus, and its use in humans for oncological treatment is being evaluated.
In the present work, we have developed two types of NDV-vectored candidate vaccines, which carry the surface-exposed RBD and S1 antigens of SARS-CoV-2, respectively. These vaccine candidates were produced in specific-pathogen-free embryonating chicken eggs, and purified from allantoic fluid before lyophilization. These vaccines were administered intranasally to three different animal models: mice, rats and hamsters, and evaluated for safety, toxicity, immunogenicity, stability and efficacy. Efficacy was evaluated in a challenge assay against active SARS-CoV-2 virus in the Golden Syrian hamster model.
The NDV-vectored vaccine based on the S1 antigen was shown to be safe and highly immunogenic, with the ability to neutralize SARS-CoV-2 in-vitro , even with an extreme dilution of 1/640. Our results reveal that this vaccine candidate protects the lungs of the animals, preventing cellular damage in this tissue. In addition, this vaccine reduces the viral load in the lungs, suggesting that it may significantly reduce the likelihood of transmission. Being lyophilized, this vaccine candidate is very stable and can be stored for several months at 4-8⁰C.
In conclusion, our NDV-based vaccine candidate has shown a very favorable performance in the pre-clinical study, serving as evidence for a future evaluation in a Phase-I human clinical trial. This candidate represents a promising tool in the fight against COVID-19.
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SciScore for 10.1101/2021.03.07.434276: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Ethics statements: Animal research was reviewed and conducted under an approved protocol by the Committee on the Ethics of Animal Experiments of the School of Veterinary and Animal Husbandry of the Universidad Nacional Hermilio Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable This study was carried out in strict accordance with the recommendations described in the Guide of biosafety and the Care and Use Animals of the National Institute of Health (INS), Lima, Peru 55. 2.2. Animals: One hundred male and female 4-5 weeks-old Golden Syrian hamsters (Mesocricetus auratus) that were, 14 female 5-8 weeks-old … SciScore for 10.1101/2021.03.07.434276: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Ethics statements: Animal research was reviewed and conducted under an approved protocol by the Committee on the Ethics of Animal Experiments of the School of Veterinary and Animal Husbandry of the Universidad Nacional Hermilio Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable This study was carried out in strict accordance with the recommendations described in the Guide of biosafety and the Care and Use Animals of the National Institute of Health (INS), Lima, Peru 55. 2.2. Animals: One hundred male and female 4-5 weeks-old Golden Syrian hamsters (Mesocricetus auratus) that were, 14 female 5-8 weeks-old albino mice (Mus musculus) strain BALB/c, and 36 male 7-9 weeks-old rats (Rattus norvegicus albinus, strain Holtzman) were obtained from the Peruvian National Institute of Health (INS). Table 2: Resources
Experimental Models: Organisms/Strains Sentences Resources This study was carried out in strict accordance with the recommendations described in the Guide of biosafety and the Care and Use Animals of the National Institute of Health (INS), Lima, Peru 55. 2.2. Animals: One hundred male and female 4-5 weeks-old Golden Syrian hamsters (Mesocricetus auratus) that were, 14 female 5-8 weeks-old albino mice (Mus musculus) strain BALB/c, and 36 male 7-9 weeks-old rats (Rattus norvegicus albinus, strain Holtzman) were obtained from the Peruvian National Institute of Health (INS). albinosuggested: NoneBALB/csuggested: NoneSoftware and Algorithms Sentences Resources To evaluate changes in hamsters’ mobility over time, non-parametric statistics using the Mann-Whitney and Kruskal-Walls tests were performed using the SciPy v1.5.2 package. SciPysuggested: (SciPy, RRID:SCR_008058)In all analyses, the statistical software STATA v. STATAsuggested: (Stata, RRID:SCR_012763)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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT03889275 Recruiting A Study of MEDI5395 in Combination With Durvalumab in Subjec… 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 19. 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.
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