https://orcid.org/0000-0003-1627-149X
Peer Review History
| Original SubmissionMarch 26, 2026 |
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PPATHOGENS-D-26-00788 LP.8.1-directed COVID-19 mRNA vaccines durably boost neutralizing antibodies and mitigate ancestral immune imprinting PLOS Pathogens Dear Dr. Ho, Thank you for submitting your manuscript to PLOS Pathogens. After careful consideration, we feel that it has merit but does not fully meet PLOS Pathogens'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 Jun 22 2026 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 plospathogens@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/ppathogens/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: * A letter that responds to each point raised by the editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. This file does not need to include responses to any formatting updates and technical items listed in the 'Journal Requirements' section below. * A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. * An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, competing interests statement, or data availability statement, please make these updates within the submission form at the time of resubmission. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. We look forward to receiving your revised manuscript. Kind regards, Jesse D Bloom, Ph.D. Guest Editor PLOS Pathogens Alexander Gorbalenya Section Editor PLOS Pathogens Sumita Bhaduri-McIntosh Editor-in-Chief PLOS Pathogens orcid.org/0000-0003-2946-9497 Michael Malim Editor-in-Chief PLOS Pathogens orcid.org/0000-0002-7699-2064 Additional Editor Comments : Thanks for submitting this valuable study to PLoS Pathogens. One of the reviewers has some constructive minor suggestions. Please incorporate those in a minor revision. I also suggest that you might add a citation and brief comparison/contrast of your results to this recent study in the Discussion (https://www.thelancet.com/action/showPdf?pii=S1473-3099%2826%2900050-2). I expect I should be able to rapidly editorially review these minor revisions, so will not need to send the paper for re-review. But do include a brief reviewer response explaining any updates. Journal Requirements: 1) We ask that a manuscript source file is provided at Revision. Please upload your manuscript file as a .doc, .docx, .rtf or .tex. If you are providing a .tex file, please upload it under the item type u2018LaTeX Source Fileu2019 and leave your .pdf version as the item type u2018Manuscriptu2019. 2) Please upload all main figures as separate Figure files in .tif or .eps format. For more information about how to convert and format your figure files please see our guidelines: https://journals.plos.org/plospathogens/s/figures 3) We have noticed that you have uploaded Supporting Information files, but you have not included a list of legends. Please add a full list of legends for your Supporting Information files after the references list. 4) Please ensure that the funders and grant numbers match between the Financial Disclosure field and the Funding Information tab in your submission form. Note that the funders and grants must be provided in the same order in both places as well. Note: If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. Reviewers' Comments: 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: Mellis et al study presents data showing changes in neutralizing titers against different SARS-CoV-2 variants post LP.8.1 booster. They find that there is a broad increase in neutralizing titers post LP.8.1 booster across different SARS-CoV-2 variants, but notably the neutralizing titers are greatest against LP.8.1 and related SARS-CoV-2 variants. This is notable because in prior studies using earlier booster strains neutralizing titers post boost were always highest against D614G variant, which suggest that LP.8.1 booster vaccine might start overcoming immune imprinting caused by the early SARS-CoV-2 variant exposure. Reviewer #2: The manuscript by Mellis et al is an excellent and important short report about the outcomes of LP.8.1 booster vaccines. A key point is that the booster is finally providing mitigating immune imprinting and providing broad protection. I have several cosmetic corrections and suggestions. ********** 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: I have no major issues, presented data justifies author conclusions. Reviewer #2: In the abstract the authors say that this is the first time since 2022 that boost titers were higher against the homologous target than the ancestor, but throughout the paper they say this is the first time that this has ever happened. Which is it? Fig 1A. The figure twice incorrectly says N478D instead of N487D. The figure neglects the addition of F456L in the XDV lineage. The figure includes LP.8.1.9 for no apparent reason. It was a minor lineage and not included in the experiments, I would remove it if there is no reason for it. For recombinants XDV and XEC the Spike was derived from the parent shown. However, XFG got half of its RBD from LF.7 and the other half from LP.8.1.2. This is why the booster worked so well against XFG (which might be worth mentioning). The way the figure is laid out is inappropriate because it makes it look like 445R, 487D and 493E were acquired through mutation rather than recombination. I would recommend rearranging the figure to show LF.7 and LP.8.1.1 contributing to XFG, perhaps indicating that 445-493 was derived from LP.8.1.1. ********** 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: (No Response) Reviewer #2: Given the high degree of convergent evolution in these lineages, I would recommend making a supplemental figure indicating what residue each lineage has at the heterogeneous positions, at least for the RBD. The data makes a lot more sense when you see it this way rather than simply based on ancestry. I think it is worth stating explicitly that the ancestral lineage had the highest titer pre-boost, but LP.8 was the highest post-boost. It also think it’s probably also worth stating explicitly that that BA.3.2 had by far the lowest titer post-boost. ********** 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:Marc Johnson [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.] Figure resubmission: -->While revising your submission, we strongly recommend that you use PLOS’s NAAS tool (https://ngplosjournals.pagemajik.ai/artanalysis) to test your figure files. NAAS can convert your figure files to the TIFF file type and meet basic requirements (such as print size, resolution), or provide you with a report on issues that do not meet our requirements and that NAAS cannot fix.-->--> After uploading your figures to PLOS’s NAAS tool - https://ngplosjournals.pagemajik.ai/artanalysis, NAAS will process the files provided and display the results in the "Uploaded Files" section of the page as the processing is complete. If the uploaded figures meet our requirements (or NAAS is able to fix the files to meet our requirements), the figure will be marked as "fixed" above. If NAAS is unable to fix the files, a red "failed" label will appear above. When NAAS has confirmed that the figure files meet our requirements, please download the file via the download option, and include these NAAS processed figure files when submitting your revised manuscript.-->--> Reproducibility: To enhance the reproducibility of your results, we recommend that authors of applicable studies deposit 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. Ho, We are pleased to inform you that your manuscript 'LP.8.1-directed COVID-19 mRNA vaccines durably boost neutralizing antibodies and mitigate ancestral immune imprinting' has been provisionally accepted for publication in PLOS Pathogens. 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, Jesse D Bloom, Ph.D. Guest Editor PLOS Pathogens Alexander Gorbalenya Section Editor PLOS Pathogens Sumita Bhaduri-McIntosh Editor-in-Chief PLOS Pathogens orcid.org/0000-0003-2946-9497 Michael Malim Editor-in-Chief PLOS Pathogens orcid.org/0000-0002-7699-2064 *********************************************************** The authors have addressed the minor comments, this paper is a valuable contribution. Reviewer Comments (if any, and for reference): |
| Formally Accepted |
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Dear Dr. Ho, We are delighted to inform you that your manuscript, "LP.8.1-directed COVID-19 mRNA vaccines durably boost neutralizing antibodies and mitigate ancestral immune imprinting," 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. For Research Articles, you will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. Thank you again for supporting open-access publishing; we are looking forward to publishing your work in PLOS Pathogens. Best regards, Sumita Bhaduri-McIntosh Editor-in-Chief PLOS Pathogens orcid.org/0000-0003-2946-9497 Michael Malim Editor-in-Chief PLOS Pathogens orcid.org/0000-0002-7699-2064 |
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