Review Comments: The research article may be a call for an awakening too, at National & Global Levels. This study is so useful for make vaccine.

1.Quote *”In this study, we first surveyed the existing coronavirus vaccine development status, and 98then applied the Vaxign RV and Vaxign-MLapproachesto predict COVID-19 protein 99candidates for vaccine development. We identified sixpossible adhesins,including the structural 100S proteinand fiveother non-structural proteins, and three of them (S, nsp3,and nsp8proteins) 101were predicted to induce high protective immunity. The S protein was predicted to have the 102highest protective antigenicity score,and it has been extensively studied as the target of 103coronavirus vaccines by other researchers. The sequence conservation and immunogenicity of 104the multi-domain nsp3 protein,which was predicted to have the second-highest protective 105antigenicity score yet, was further analyzed in this study.“• End of Quote.

The authors seem to be suggesting a global revers vaccinology.

1. Quote “To better understand the current status of coronavirus vaccine development, we systematically surveyed the development of vaccines for coronavirus from the ClinicalTrials.gov database and PubMed literature(as of March 17, 2020). Extensive effort has been made to develop a safe and effective vaccine against SARS or MERS, and the most advance clinical trial study is currently at phase II(Table 1). Itis a challenging task to quickly develop a safe and effective vaccine for the on-going COVID-19 pandemic. There are two primarydesign strategies for coronavirus vaccine development: the usage of the whole virus or genetically engineered vaccine antigens that can be delivered through different formats”. End of Quote.

The authors so explain part of Vaxign reserve vaccinology. The authors then explain a timely analysis for the vaccine development against COVID- 19.

3.Quote ”However, these predicted on-structural proteins (nasp3, 3CL-pro, nsp8, nsp9, and nsp10) are not part of the viral structural particle, and all the current SARS/MERS/COVID-19 vaccine studies target the structural (S/M/N) proteins. Although structural proteins are commonly used as viral vaccine candidates, non-structural proteins correlates to vaccine protection. The non-structural proteinNS1was found to induce protective immunity against the infections by flaviviruses” End of Quote.

4.Quote ”Immunogenicity analysis.The immunogenicity of the nsp3 protein was evaluated by the prediction of T cell MHC-I and MHC-II, and linear B cell epitopes. For T cell MHC-I epitopes, the IEDB consensus method was used to predicting promiscuous epitopes binding to 4 out of 27 MHC-I reference alleles with consensus percentile ranking less than 1.0score53. For T cellMHC-II epitopes, the IEDB consensus method was used to predicting promiscuous epitopes binding to more than half of the 27 MHC-II reference alleles with consensus percentile ranking less than 10.0. The MHC-I and MHC-II reference alleles covered a wide range of human genetic variation representing the majorityof the world population66,67.The linear B cell epitopes were predicted using the BepiPred 2.0 with a cutoff of 0.55score68. Linear B cell epitopes with at least tenamino acids were mapped to the predicted 3D structure of SARS-CoV-2 nsp3 protein visualized via PyMol69.“ End of Quote.

The list of Conformational epitopes are used for predicting vaccine. The components in this research are: A curated genomic resource. A server for prediction of epitopes. A knowledge-Base for study. A server for variability analyses.