PREreview of Preclinical Evaluation of a Newcastle Disease Virus-Vectored Intranasal SARS-CoV-2 Vaccine

A brief overview of the paper and its main findings

First of all, I would like to thank all authors for their invaluable effort to improve Peruvian scientific research. This study shows the results of the preclinical evaluation of a candidate for the COVID-19 vaccine. This proposal was entirely produced in Peru and used a viral vector, the Newcastle virus, which causes respiratory disease in chickens. The main novelty of this proposal is their administration in an intranasal way.

Major points

1. There is interesting the use of Syrian hamsters as a study model. It was announced by various articles mentioning similarities between Syrian hamsters and humans on COVID-19 disease. The response to SARS-CoV-2 infection of these animals usually increases in aged (instead of young) individuals, as happens in humans. In your text, you described the use of younger Golden Syrian hamsters (4-5 weeks old) instead of aged ones as other studies have performed (DOI: 10.1038/s41541-021-00321-8 and 10.1073/pnas.2014468117). Therefore I believe that the age of these animals could influence the interpretation of histopathological results. You may found more information about this on PMC7412213 and PMID32571934 to support you in the discussion section.
2. In Figure 9A, there is hope to see higher levels (above 80%) of viral isolate for all cases in 2 dpi. There would be interesting to see possible reasons for having hamsters with almost zero percent of viral isolation at that moment. Also, I think it important to see a statistical comparison between 2-5-10 dpi, at least for the most important candidate in your proposal (rLS1-S1-F).
3. Then in the text, you wrote: "This is consistent with previous studies, which reported that viral load is reduced to undetectable levels by 8 days after infection in the hamster animal model". Today we know that viral load is detectable up to 14 days after infection in Syrian hamsters. I think different factors (as the age and sex of these animals) would intermediate this fluctuation. Probably, you should update this information on your preprint, especially on the discussion.
4. You also wrote: "Being lyophilized, this vaccine candidate is very stable and can be stored for several months at 4-8⁰C". However, I think there is not sufficient evidence to say this by your western blot with products stored up to 50 days. You could attach results of the biological effect of previously-stored vaccine candidates. Also, you may consider testing candidate vaccines stored for more than 2 months.

Minor points

1. In a general view, I suggest showing more technical details, such as information about qPCR efficiency curves (or efficiency ranges) for all studied genes.