Multi-epitope vaccine design using in silico analysis of glycoprotein and nucleocapsid of NIPAH virus

Anoop Kumar; Gauri Misra; Sreelekshmy Mohandas; Pragya D. Yadav

doi:10.1371/journal.pone.0300507

Peer Review History

Original SubmissionDecember 9, 2023
26 Jan 2024 Decision Letter - Sheikh Arslan Sehgal, Editor PONE-D-23-41371Multi-Epitope Vaccine Design Using in silico analysis of Glycoprotein and Nucleocapsid of NIPAH virusPLOS ONE Dear Dr. Kumar, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Mar 11 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Partly Reviewer #2: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/A Reviewer #2: N/A ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. 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(Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Dear authors please consider the mentioned comments related to manuscript entitled “Multi-Epitope Vaccine Design Using in silico analysis of Glycoprotein and Nucleocapsid of NIPAH virus” 1. Please mention in the manuscript the threshold, accuracy and URL for all used servers in epitopes selection and vaccine design. Also the references for all used servers should be mentioned in manuscript. 2. The conformational B cell epitopes should be selected. 3. This is a bioinformatics study, so it is better to change the section of materials and methods to methods. 4. Please, the authors answer to this question, what is the reason for doing docking with different TLRs (3, 7, and 8)? 5. It is suggested to refer to the following paper in the use section of the EAAAK, GPGPG and kk linkers. https://pubmed.ncbi.nlm.nih.gov/37146081/ 6. The references should be updated. Reviewer #2: Overall, these suggestions aim to improve the clarity, accessibility, and impact of the manuscript, and I look forward to seeing these enhancements in the revised version. Thank you for your valuable contribution to the field. 1. Authors should use more specialized words for the manuscript. Unfortunately, inappropriate terms such as "projected epitopes" are used in some parts of the manuscript. The manuscript must be checked and corrected by an expert. 2. The words “in silico”, “in vivo” and “in vitro” should be written in italics throughout the manuscript. 3. Figure 1 is not very satisfactory, it is suggested to draw an attractive flowchart to present the working method. 4. In lines 104, 105, 172 , 384, and Table 4 after IFN, put gamma characters. 5. In the materials and methods section, the authors must provide sources for all used servers and give them citations. 6. For some sentences like " As an adjuvant, CTB has been found to increase the production of antigen-specific antibodies and stimulate the activation of T-cells, leading to a more robust and effective immune respons", no reference is mentioned. Please be sure to mention the relevant source for all these sentences. 7. Among the physicochemical properties, the instability index parameter is an important and decisive parameter that the authors did not report. 8. In order to complete the article, the authors must predict discontinuous B-cell epitope on the three-dimensional structure of the vaccine and present the results in the manuscript. 9. To complete the paper, the authors must perform disulfide engineering of the 3D structure of the vaccine and present the results in the manuscript. 10. For the richness of the study, the authors should compare their results with the results of other studies in the field of vaccine design, it is suggested to use the following studies for this purpose. https://doi.org/10.1371/journal.pone.0286224 https://doi.org/10.1080/07391102.2023.2258403 https://doi.org/10.3390%2Fvaccines11020263 https://doi.org/10.2174/1573409919666230612125440 https://doi.org/10.1007/s12033-023-00949-y https://doi.org/10.1038/s41598-022-11851-z ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Shirin Mahmoodi Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. Attachments Attachment Submitted filename: comment.docx https://doi.org/10.1371/journal.pone.0300507.r001
Revision 1
24 Feb 2024 Author Response Response to the Reviewers The authors are grateful to the Reviewers for the time devoted to the review of the manuscript entitled “Multi-Epitope Vaccine Design Using in silico analysis of Glycoprotein and Nucleocapsid of NIPAH virus” (ID: PONE-D-23-41371). We have carefully considered the comments and observations as well as the suggestions given in the reports and suitably modified the original text in order to address them to our best. The suggested changes are highlighted in track change mode in the revised manuscript. Detailed responses to the different points raised by the Reviewers are given below. 1. Please mention in the manuscript the threshold, accuracy and URL for all used servers in epitopes selection and vaccine design. Also the references for all used servers should be mentioned in manuscript. Ans: As suggested by the reviewer, the needful has been done at the required places. 2. The conformational B cell epitopes should be selected. Ans: As suggested by the reviewer, conformational B cell epitopes has been predicted using ellipro tool (http://tools.iedb.org/ellipro/) of IEDB and results has been incorporated in the manuscript. 3. This is a bioinformatics study, so it is better to change the section of materials and methods to methods. Ans: As suggested by the reviewer, the materials and methods now changed as Methodology. 4. Please, the authors answer to this question, what is the reason for doing docking with different TLRs (3, 7, and 8)? Ans: TLRs are specifically accountable for the detection of viruses and the initiation of innate immunity, which is succeeded by adaptive immunity. Thus, they play a crucial role in innate immunity. TLR3, TLR7, and TLR8 are capable of identifying ds/ssRNA, a prevalent intermediary in the replication process of numerous RNA viruses (Chuang, T. H., and R. J. Ulevitch. 2000.; Lester SN, 2014). Docking investigations play a pivotal role in comprehending the molecular interactions that regulate immune responses. By simulating the initial recognition stages of the immune system, signaling pathways are stimulated, which ultimately contributes to the development of a robust immune response. In order to enhance the immune response, vaccine adjuvants frequently target TLRs for stimulation. Gaining insight into the manner in which vaccine constructs engage with particular TLRs can enhance the effectiveness of vaccines, customize immune responses, and facilitate the development of personalized vaccines. These studies additionally offer mechanistic understandings regarding the mechanisms by which vaccine constructs stimulate TLRs, thereby improving immunogenicity and informing the development of constructs that stimulate more robust and targeted immune responses (Lester SN, 2014). 5. It is suggested to refer to the following paper in the use section of the EAAAK, GPGPG and KK linkers. https://pubmed.ncbi.nlm.nih.gov/37146081/ Ans: As suggested by the reviewer, needful has been done. 6. The references should be updated. Ans: As suggested by the reviewer, references have been updated. Reviewer #2: Overall, these suggestions aim to improve the clarity, accessibility, and impact of the manuscript, and I look forward to seeing these enhancements in the revised version. Thank you for your valuable contribution to the field. 1. Authors should use more specialized words for the manuscript. Unfortunately, inappropriate terms such as "projected epitopes" are used in some parts of the manuscript. The manuscript must be checked and corrected by an expert. Ans: Thanks for the reviewer comment, the terms have been changed and needful has been done. 2. The words “in silico”, “in vivo” and “in vitro” should be written in italics throughout the manuscript. Ans: Thanks for the reviewer comment, “in silico”, “in vivo” and “in vitro” has been change to italics. 3. Figure 1 is not very satisfactory; it is suggested to draw an attractive flowchart to present the working method. Ans: Thanks for the reviewer comment, figure has been changed and flowchart has been incorporated. 4. In lines 104, 105, 172, 384, and Table 4 after IFN, put gamma characters. Ans: Thanks for the reviewer comment, the gamma character has been incorporated as required places. 5. In the materials and methods section, the authors must provide sources for all used servers and give them citations. Ans: Thanks for the reviewer comment, sources for all servers used in the study and their citations has incorporated in methodology section. 6. For some sentences like " As an adjuvant, CTB has been found to increase the production of antigen-specific antibodies and stimulate the activation of T-cells, leading to a more robust and effective immune response", no reference is mentioned. Please be sure to mention the relevant source for all these sentences. Ans: Thanks for the reviewer comment, the citations have been incorporated at the required places in the manuscript. 7. Among the physicochemical properties, the instability index parameter is an important and decisive parameter that the authors did not report. Ans: Thanks for the reviewer comments, instability index parameter has been incorporated in line no 260 “computed instability index of 28.56 indicates that the construct is stable” 8. In order to complete the article, the authors must predict discontinuous B-cell epitope on the three-dimensional structure of the vaccine and present the results in the manuscript. Ans: As suggested by the reviewer, conformational B cell epitopes has been predicted using ellipro tool (http://tools.iedb.org/ellipro/) of IEDB and results has been incorporated in the manuscript. 9. To complete the paper, the authors must perform disulfide engineering of the 3D structure of the vaccine and present the results in the manuscript. Ans: Thanks for the reviewer comments, disulfide engineering of the 3D structure of the vaccine has been predicted and result has been incorporated. “The vaccine construct's model identify 32 residue pairs that may potentially create a disulfide bond, as predicted by the Disulfide by Design 2.13 server (Table 8). As per study by Craig DB, et al., for the formation of disulfide bonds the χ3 angle lies between -87˚ and +97˚ and energy value less than 2.2 kcal/mol, on the basis of the this only two amino acid pair (335-GLY-373-GLY & 24-GLN-28-ASP) were form the disulfide bond in the designed construct (Table 8). 10. For the richness of the study, the authors should compare their results with the results of other studies in the field of vaccine design, it is suggested to use the following studies for this purpose. Ans: Thanks for the reviewer valuable comments, new refences has been incorporated and the discussion has been modified. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0300507.r002
29 Feb 2024 Decision Letter - Sheikh Arslan Sehgal, Editor Multi-Epitope Vaccine Design Using in silico analysis of Glycoprotein and Nucleocapsid of NIPAH virus PONE-D-23-41371R1 Dear Dr. Kumar, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Sheikh Arslan Sehgal, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0300507.r003
Formally Accepted
29 Apr 2024 Acceptance Letter - Sheikh Arslan Sehgal, Editor PONE-D-23-41371R1 PLOS ONE Dear Dr. Kumar, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr Sheikh Arslan Sehgal Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0300507.r004

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