https://orcid.org/0000-0001-9622-5834
Peer Review History
| Original SubmissionFebruary 25, 2021 |
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Dear Dr. Zhang, Thank you very much for submitting your manuscript "Pore-forming alpha-hemolysin efficiently improves the immunogenicity and protective efficacy of protein antigens" for consideration at PLOS Pathogens. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. In light of the reviews (below this email), we would like to invite the resubmission of a significantly-revised version that takes into account the reviewers' comments. We cannot make any decision about publication until we have seen the revised manuscript and your response to the reviewers' comments. Your revised manuscript is also likely to be sent to reviewers for further evaluation. When you are ready to resubmit, please upload the following: [1] A letter containing a detailed list of your responses to the review comments and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. [2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file). Important additional instructions are given below your reviewer comments. Please prepare and submit your revised manuscript within 60 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. Please note that revised manuscripts received after the 60-day due date may require evaluation and peer review similar to newly submitted manuscripts. Thank you again for your submission. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments. Sincerely, Rachel M McLoughlin, PhD Associate Editor PLOS Pathogens Alan Hauser Section Editor PLOS Pathogens Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens *********************** Reviewer's Responses to Questions Part I - Summary Please use this section to discuss strengths/weaknesses of study, novelty/significance, general execution and scholarship. Reviewer #1: In this manuscript “Pore-forming alpha-hemolysin efficiently improved the immunogenicity and protective efficacy of protein antigens”, Zou et al describe the use of a mutated form of the S. aureus protein Hla as a protein carrier for fusion to antigens used for immunization. The data suggests that the fusion proteins, when combined with alum, can offer substantial protection (100% survival and over 3 log reduction in bacterial burden) from infection with P. aeruginosa. The authors go on to show that the Hla-fusion proteins can induce robust antigen-specific IgG responses, in addition to cytokine responses. They show that antigen uptake occurs by monocytes, macrophages and neutrophils all uptaking the antigen. Overall, this is a concise and well-written manuscript with robust data. Reviewer #2: This study by Zou and colleagues tests a novel hemolysin and pseudomonas antigen fusion protein as a novel vaccine platform. The strength of the study is mainly in the innovation of this construct. The data in mice show increased antibody responses compared to immunization with the pseudomonas antigen alone and also impressive enhancement of protective immunity, but only in the presence of alum. The protective immunity is not improved without alum as shown in Figures 1C and 1D. In addition, to achieve this effect three immunization are necessary. The immunity is not tested against other pseudomonas antigen, only one mouse strain and one sex are tested. This limits the enthusiasm for the potential applicability of this platform. The cellular response studies in muscle and lymph nodes seem mostly dependent on the alum effect. Also, the conclusion that there is an increased Th2 response is only based on slightly increased IgG1 titers. The relevance of the in vitro studies is limited by the use of tumor cell lines. Reviewer #3: The authors described a fused protein as potential vaccine candidate. Several fused proteins including chimeric and trimeric vaccines were previously described. The authors did not show the advantage of their fused protein compared to other vaccine candidates against pseudomonas. ********** Part II – Major Issues: Key Experiments Required for Acceptance Please use this section to detail the key new experiments or modifications of existing experiments that should be absolutely required to validate study conclusions. Generally, there should be no more than 3 such required experiments or major modifications for a "Major Revision" recommendation. If more than 3 experiments are necessary to validate the study conclusions, then you are encouraged to recommend "Reject". Reviewer #1: The authors did not compare their HPF to one of the well-established protein carriers like diphtheria toxin or tetanus toxoid to test if Hla is indeed a superior protein carrier than molecules with known safety profiles. Without these data, it is hard to gauge the potential impact of the presented findings. The lack of DC recruitment to the injection site is puzzling and may need to be further investigated. Reviewer #2: Confirmation of the enhancement of protective and Th2 immunity in a different haplotype. Clearer delineation of the alum dependent responses. Reviewer #3: -Complement mediated killing has a major role in clearance of Gram negative bacteria including pseudomonas species. The authors did not show how complement functional activity affected before and after immunisation. -The authors cloned 2 coding sequences in one expression vector.Would you please describe this in details. Did you express the fused protein under control of one promotor or your vector has two different promotors. -The discussion section is poorly written and the authors did not high light other vaccine candidates against pseudomonas. ********** Part III – Minor Issues: Editorial and Data Presentation Modifications Please use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. Reviewer #1: Could the authors use and ADAM10 inhibitor and show that the response to the fusion protein is diminished, therefore directly linking the increased response of using Hla to the binding of ADAM10? Reviewer #2: (No Response) Reviewer #3: -The resolution of the figures is not good - English language editing is also required in some section. ********** 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: No Reviewer #2: Yes: Stefan Worgall Reviewer #3: No Figure 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. 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 us at figures@plos.org. Data Requirements: Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example see here on PLOS Biology: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5. Reproducibility: To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols |
| Revision 1 |
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Dear Dr. Zhang, We are pleased to inform you that your manuscript 'Pore-forming alpha-hemolysin efficiently improves the immunogenicity and protective efficacy of protein antigens' has been provisionally accepted for publication in PLOS Pathogens subject to you addressing the outstanding reviewers comments included below. Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests. Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated. IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript. Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS. Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Pathogens. Best regards, Rachel M McLoughlin, PhD Associate Editor PLOS Pathogens Alan Hauser Section Editor PLOS Pathogens Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens *********************************************************** Reviewer Comments (if any, and for reference): The figure legends and description of the results should be clear on which mouse strain was used for the respective experiments. The lack of testing of other promising Pseudomonas proteins should be discussed as a potential weakness of this study There is still a question of how much improved this platform really is compared to others. |
| Formally Accepted |
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Dear Dr. Zhang, We are delighted to inform you that your manuscript, "Pore-forming alpha-hemolysin efficiently improves the immunogenicity and protective efficacy of protein antigens," has been formally accepted for publication in PLOS Pathogens. We have now passed your article onto the PLOS Production Department who will complete the rest of the pre-publication process. All authors will receive a confirmation email upon publication. The corresponding author will soon be receiving a typeset proof for review, to ensure errors have not been introduced during production. Please review the PDF proof of your manuscript carefully, as this is the last chance to correct any scientific or type-setting errors. Please note that major changes, or those which affect the scientific understanding of the work, will likely cause delays to the publication date of your manuscript. Note: Proofs for Front Matter articles (Pearls, Reviews, Opinions, etc...) are generated on a different schedule and may not be made available as quickly. Soon after your final files are uploaded, the early version of your manuscript, if you opted to have an early version of your article, will be published online. The date of the early version will be your article's publication date. The final article will be published to the same URL, and all versions of the paper will be accessible to readers. Thank you again for supporting open-access publishing; we are looking forward to publishing your work in PLOS Pathogens. Best regards, Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens |
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