Antibody response to tetanus, diphtheria, poliomyelitis, hepatitis B, and H. influenzae b vaccines in allogeneic hematopoietic stem cell transplant adult recipients: A multicenter trial

Olivier Epaulard; Martin Carré; Eric Hermet; Violaine Corbin; Emmanuelle Tavernier; Elisabeth Botelho-Nevers; Etienne Daguindau; Anne-Sophie Brunel; Pierre-Simon Rohrlich; Karine Risso; Salomé Gallet; Nicolas Gonnet; Saber Touati; Marc Manceau; Anne Thiebault

doi:10.1371/journal.pone.0335224

Peer Review History

Original SubmissionJuly 20, 2025
15 Sep 2025 Decision Letter - Ray Borrow, Editor Dear Dr. Epaulard, Please submit your revised manuscript by Oct 30 2025 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. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. 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. 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Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. We note that you have indicated that there are restrictions to data sharing for this study. For studies involving human research participant data or other sensitive data, we encourage authors to share de-identified or anonymized data. However, when data cannot be publicly shared for ethical reasons, we allow authors to make their data sets available upon request. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Before we proceed with your manuscript, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., a Research Ethics Committee or Institutional Review Board, etc.). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of recommended repositories, please see https://journals.plos.org/plosone/s/recommended-repositories. You also have the option of uploading the data as Supporting Information files, but we would recommend depositing data directly to a data repository if possible. Please update your Data Availability statement in the submission form accordingly. 3. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. 4. Thank you for stating the following financial disclosure: This study was funded by the national French hospital research program (PHRC) (Grant N° PHRCI-16-016). Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. 5. Please note that funding information should not appear in any section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript. 6. 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. 7. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? Reviewer #1: Partly Reviewer #2: Partly Reviewer #3: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: Yes Reviewer #2: I Don't Know Reviewer #3: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** Reviewer #1: The manuscript #PONE-D-25-32490 titled “Antibody response to tetanus, diphtheria, poliomyelitis, hepatitis B, and H. influenzae b vaccines in allogeneic hematopoietic stem cell transplant adult recipients: A multicenter trial” described antibody response to tetanus, diphtheria, hepatitis B, polio and H. influenzae b after 4 doses of DTaP-HBV-Hib-IPV in adults after hematopoietic stem cell transplant. The study was interesting. I have the following comments, 1. In my opinion, a lot of studies have demonstrated good response of immune response after vaccination in patients after HSCT. The authors may have raise the novel issues this study contributed to. 2. In result part, the percentages of patients having protected antibody seemed to decrease in tetanus, diphtheria, polio. What would be the explanation of these results? In addition, why were the percentages of patients not protected for pathogens higher after the booster dose compared with after the 3rd dose? In fact, these percentages should be lower after the booster dose. Did some of these patients get additional immunosuppressive drugs during the vaccination course? 3. Did the presence of GvHD affect immune response to vaccination? 4. Concomitant vaccinations should be presented. 5. Minor grammatical correction should be performed. Reviewer #2: Considering that the 2 vaccines used have different formulations (DTap2 vs DTap3) and that the immunogenicity values differ in both, should they have been analyzed independently in order to decide withether DTaP 3 is better or not (Hexavalent vaccines: What can we learn from head-to-head studies? Markus Knuf , Hervé Haas, Pilar Garcia-Corbeira , Elisa Turriani , Piyali Mukherjee ,Winnie Janssens , Valérie Berlaimont Vaccine Volume 39, Issue 41, 1 October 2021, Pages 6025-6036)(Hexavalent CMIvaccines for immunization in paediatric age S. Esposito, C. Tagliabue, S. Bosis, V. Ierardi, M. Gambino and N. Principi Clinical Microbiology and Infection, Volume 20 Supplement 5, May 2014 76-85 Reviewer #3: Useful research and give good protection to the transplant patients . Excellent efforts .and choosing these type of research is really needed to the dither generation . Transplant patient survival and morbidity free survival is very important and for that this research is very useful . ****** 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: Dr.M.D.Ravi Reviewer #3: Yes: Inumarthi Vara Padmavathi ******** [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 Attachments Attachment Submitted filename: Hexavalent vaccines for immunization.pdf Attachment Submitted filename: 1-s2.0-S0264410X21011464-main.pdf https://doi.org/10.1371/journal.pone.0335224.r001
Revision 1
25 Sep 2025 Author Response Manuscript PONE-D-25-32490 Antibody response to tetanus, diphtheria, poliomyelitis, hepatitis B, and H. influenzae b vaccines in allogeneic hematopoietic stem cell transplant adult recipients: A multicenter trial Response to editorial comments 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf We ensured this. 2. We note that you have indicated that there are restrictions to data sharing for this study. For studies involving human research participant data or other sensitive data, we encourage authors to share de-identified or anonymized data. However, when data cannot be publicly shared for ethical reasons, we allow authors to make their data sets available upon request. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Before we proceed with your manuscript, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., a Research Ethics Committee or Institutional Review Board, etc.). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. We created a totally de-identified set of data and deposit it on the OST (Center for Open Science) repository, with the DOI 10.17605/OSF.IO/KYDU6 on the OSF repository (osf.io). b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of recommended repositories, please see https://journals.plos.org/plosone/s/recommended-repositories. You also have the option of uploading the data as Supporting Information files, but we would recommend depositing data directly to a data repository if possible. Please update your Data Availability statement in the submission form accordingly. We added this statement at the end of the manuscript. 3. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. We harmonized the way things were presented in the manuscript and on the submission website. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. We ensured this. 4. Thank you for stating the following financial disclosure: This study was funded by the national French hospital research program (PHRC) (Grant N° PHRCI-16-016). Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. This statement is correct. We added this sentence in the revised version of the manuscript. 5. Please note that funding information should not appear in any section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript. We removed the other funding-related text in the revised version of the manuscript. 6. 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. We did not cite new articles in the revised version of the manuscript. 7. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. We performed this review. Particularly, no retracted articles were cited. Response to reviewers' comments Reviewer #1 The manuscript #PONE-D-25-32490 titled “Antibody response to tetanus, diphtheria, poliomyelitis, hepatitis B, and H. influenzae b vaccines in allogeneic hematopoietic stem cell transplant adult recipients: A multicenter trial” described antibody response to tetanus, diphtheria, hepatitis B, polio and H. influenzae b after 4 doses of DTaP-HBV-Hib-IPV in adults after hematopoietic stem cell transplant. The study was interesting. I have the following comments, 1. In my opinion, a lot of studies have demonstrated good response of immune response after vaccination in patients after HSCT. The authors may have raise the novel issues this study contributed to. Only few studies assessed the antibody response to 5 pathogens/diseases vaccines in adult HSCT recipients (1 when this study was designed, and 3 when the manuscript was submitted to PLOS One). We added a sentence in the discussion to enlighten this novelty. 2. In result part, the percentages of patients having protected antibody seemed to decrease in tetanus, diphtheria, polio. What would be the explanation of these results? The decrease is very low, or non-existent, between months 3 and 13 (tetanus: 97.2% and 97.5%, diphtheria: 100% and 97.5%, polio: 96.6% and 92.7%). It may be debatable to speculate on such a small difference. In addition, why were the percentages of patients not protected for pathogens higher after the booster dose compared with after the 3rd dose? In fact, these percentages should be lower after the booster dose. Did some of these patients get additional immunosuppressive drugs during the vaccination course? For this parameter too, the differences are very limited (and the proportion of non-protected are low, less than 5%), and may reflect the non-protection of a single one participant; we are maybe not sure that we should comment in the “Discussion” section such tiny variations. 3. Did the presence of GvHD affect immune response to vaccination? As we excluded patients with a current GvHD, we did not have this data. However, we did not analyze the impact of a past GvHD. This has would indeed be relevant; it is a limitation, and we noted this in the “Discussion” section of the revised manuscript. 4. Concomitant vaccinations should be presented. This indeed important. We do not have the data for each patient. For example, anti-meningococcal vaccination (B vaccine, conjugated polysaccharide tetravalent ACWY vaccine) is generally initiated alongside with the hexavalent vaccination; according to the season, influenza vaccine could be also co-administered; Covid-19 vaccine boost may have also been co-administered. We add this point in the revised version of the manuscript. 5. Minor grammatical correction should be performed. Thank you for this remark. We performed these corrections. Reviewer #2 Considering that the 2 vaccines used have different formulations (DTap2 vs DTap3) and that the immunogenicity values differ in both, should they have been analyzed independently in order to decide withether DTaP 3 is better or not (Hexavalent vaccines: What can we learn from head-to-head studies? Markus Knuf , Hervé Haas, Pilar Garcia-Corbeira , Elisa Turriani , Piyali Mukherjee ,Winnie Janssens , Valérie Berlaimont Vaccine Volume 39, Issue 41, 1 October 2021, Pages 6025-6036)(Hexavalent CMIvaccines for immunization in paediatric age S. Esposito, C. Tagliabue, S. Bosis, V. Ierardi, M. Gambino and N. Principi Clinical Microbiology and Infection, Volume 20 Supplement 5, May 2014 76-85 The reviewer probably refers to names such as DT3aP-HBV-IPV/Hib used in the cited GSK article (we did no use tetravalent vaccines (DTap) but only hexavalent vaccines). Indeed, several hexavalent vaccines were used during the study, as we did not restrict the study to one vaccine manufacturer (this would have led to increase too much the study costs, considering the funding received). This heterogeneity may have led to difference in vaccine immunogenicity, but in a way almost impossible to assess, as different vaccines may have been used in the same patient. However, this heterogeneity reflects the “real world” immunization practice, where hospital pharmacy may change from one year to another the manufacturer for a vaccine. We acknowledged this important point in the revised version of the manuscript (it was already acknowledged [“the 2 vaccine combinations we used (Infanric hexa® and Hexyon®) are no totally identical in antigen quantities of Haemophilus influenzae type b polysaccharide, of diphtheria toxoid, of inactivated poliomyelitis virus”], but we stressed more this point). Reviewer #3 Useful research and give good protection to the transplant patients . Excellent efforts .and choosing these type of research is really needed to the dither generation . Transplant patient survival and morbidity free survival is very important and for that this research is very useful . Thank you for this comment. Attachments Attachment Submitted filename: Response to editorial comments.docx https://doi.org/10.1371/journal.pone.0335224.r002
29 Sep 2025 Decision Letter - Ray Borrow, Editor Dear Dr. Epaulard, 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 below during the review process. Please submit your revised manuscript by Nov 13 2025 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. A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. 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, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols . We look forward to receiving your revised manuscript. Kind regards, Ray Borrow, Ph.D., FRCPath Academic Editor PLOS ONE Journal Requirements: 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. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author Reviewer #1: (No Response) Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions??> Reviewer #1: Yes Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: Yes Reviewer #2: I Don't Know ****** 4. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes ****** Reviewer #1: The manuscript #PONE-D-25-32490R1 titled “Antibody response to tetanus, diphtheria, poliomyelitis, hepatitis B, and H. influenzae b vaccines in allogeneic hematopoietic stem cell transplant adult recipients: A multicenter trial” described antibody response to tetanus, diphtheria, hepatitis B, polio and H. influenzae b after 4 doses of DTaP-HBV-Hib-IPV in adults after hematopoietic stem cell transplant. In my opinion, the previous issues were not quite well addressed. 1. In my opinion, no novel issues were pointed out from the existing knowledge. At least, please consider this reviewed article; doi: 10.3390/cancers13236140. 2. In result part, the percentages of patients having protected antibody seemed to decrease in tetanus, diphtheria, polio. What would be the explanation of these results? This should be better addressed. 3. Did the presence of GvHD affect immune response to vaccination? Previous GvHD could affect later immune response as immune reconstitution may be delayed. Addressing only CD19+ level and immunoglobulin level are not enough. T cell subset numbers or functions are also important in immune response. 4. Concomitant vaccinations should be presented. Interference of other vaccines may affect immune response. This should be clearly presented. Reviewer #2: The terms DTaP 2 and DTaP 3 referred to the number of acellular pertussis components in the hexavalent vaccine. A large number of vaccine studies have used correlates of immunity aaginst pertussis - also accepted by vaccine regulatory bodies. Considering that it is re-emerging in a big way, I think this should have been looked at ****** 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: Dr M.D Ravi ******** [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. https://doi.org/10.1371/journal.pone.0335224.r003
Revision 2
7 Oct 2025 Author Response PONE-D-25-32490R1 Antibody response to tetanus, diphtheria, poliomyelitis, hepatitis B, and H. influenzae b vaccines in allogeneic hematopoietic stem cell transplant adult recipients: A multicenter trial The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Responses to Review Comments to the Author (Revision N°2) Reviewer #1 The manuscript #PONE-D-25-32490R1 titled “Antibody response to tetanus, diphtheria, poliomyelitis, hepatitis B, and H. influenzae b vaccines in allogeneic hematopoietic stem cell transplant adult recipients: A multicenter trial” described antibody response to tetanus, diphtheria, hepatitis B, polio and H. influenzae b after 4 doses of DTaP-HBV-Hib-IPV in adults after hematopoietic stem cell transplant. In my opinion, the previous issues were not quite well addressed. 1. In my opinion, no novel issues were pointed out from the existing knowledge. At least, please consider this reviewed article; doi: 10.3390/cancers13236140. This comment is a bit surprising, as we are currently at the “revision” part of the process; meanwhile, this remark is understandable in the “initial submission” part of the process, not in the revision version (indeed, the data we reported in the revised version are not more or less “novel” than in the initial submission of the manuscript). Moreover, as mentioned in the manuscript, this clinical trial brings immunogenicity data regarding the vaccine response in a rarely studied population: adult HSCT recipients. Only few studies reported such data (response to diphtheria, tetanus, polio vaccines: 4 studies, all smaller than ours; response to Haemophilus: 5 studies, all smaller than ours; response to hepatitis B in non-infected subjects: 2 studies, one being smaller than ours) in these subjects. However, we modified again the R2 version of the manuscript to make this clearer, and added citations concerning small (N<30) studies. Regarding the suggesting citation: the title is very interesting and promising, but we usually do not cite predatory editors, and therefore we prefer not to cite manuscripts published by MDPI journals (https://www.predatoryjournals.org/news/is-mdpi-predatory; https://en.wikipedia.org/wiki/MDPI#Controversies), as giving publicity to such problematic stakeholders may be considered malpractice. 2. In result part, the percentages of patients having protected antibody seemed to decrease in tetanus, diphtheria, polio. What would be the explanation of these results? This should be better addressed. We had stated in the “response to reviewers” document during the R1 revision process that “The decrease is very small, or non-existent, between months 3 and 13 (tetanus: 97.2% to 97.5%, diphtheria: 100% to 97.5%, polio: 96.6% to 92.7%). It may be debatable to speculate on such a small difference”. 3. Did the presence of GvHD affect immune response to vaccination? Previous GvHD could affect later immune response as immune reconstitution may be delayed. This is indeed an important remark. We had already stated in the “response to reviewers” document that “As we excluded patients with a current GvHD, we did not have this data. However, we did not analyze the impact of a past GvHD. This has would indeed be relevant; it is a limitation, and we noted this in the “Discussion” section of the revised manuscript”. On the other hand, we previously did not exploit the data available to us concerning the presence of non-severe GvHD at inclusion. We therefore did these analyses in the recent days and did not observe any difference between those with or without GvHD at inclusion. We added this result in the revised (R2) manuscript. Addressing only CD19+ level and immunoglobulin level are not enough. T cell subset numbers or functions are also important in immune response. This is an important remark, and indeed, we also measured TCD3, 4 and 8 lymphocytes populations in the participants, alongside with CD19. As stated since the initial submission of the manuscript, “For all vaccines, we observed that the antibody level at M13 did not significantly differ according to age, sex, type of hematological malignancy, delay between transplantation and vaccination, type of transplant conditioning, or (except when mentioned below) blood levels of gammaglobulins, CD4+ T lymphocytes, or CD8+ T lymphocytes at inclusion. The only association that emerged from multivariate linear regression linked the anti-diphtheria antibody level to CD8+ T lymphocytes and the anti-H. influenzae b antibody level to both gammaglobulins and CD8+ T lymphocytes”. 4. Concomitant vaccinations should be presented. Interference of other vaccines may affect immune response. This should be clearly presented. We had stated in the “response to reviewers” document during the R1 revision process that “This is indeed important. [However, ] we do not have the data for each patient. For example, anti-meningococcal vaccination (B vaccine, conjugated polysaccharide tetravalent ACWY vaccine) is generally initiated alongside with the hexavalent vaccination; according to the season, influenza vaccine could be also co-administered; Covid-19 vaccine boost may have also been co-administered. We add this point in the revised version of the manuscript.” We still thing that this comment is very relevant, but we still do not have the data. We have let in the revised (R2) version of the manuscript the sentence we had already introduced in the R1 revised version to acknowledge this (“We did not collect if (and which) other vaccines (e.g., meningococcus, pneumococcus, influenza, or Covid-19) were performed at the same time as the study injections”) and we added a sentence in the discussion section of the revised (R2) version of the manuscript. Reviewer #2 The terms DTaP 2 and DTaP 3 referred to the number of acellular pertussis components in the hexavalent vaccine. A large number of vaccine studies have used correlates of immunity aaginst pertussis - also accepted by vaccine regulatory bodies. Considering that it is re-emerging in a big way, I think this should have been looked at. This remark is very relevant: the issue of pertussis re-emergence is indeed concerning. Alas, when we designed this study, we decided not to analyze anti-pertussis antibody response. We may regret this, but we cannot produce analyses from data we purposely did not collect. On this matter, we have let in the revised (R2) version of the manuscript the sentence we had already introduced in the R1 revised version to acknowledge this (“In addition, we did not assess the immune response to pertussis, which is currently reemerging; studies reported a lower immune response (68% seroprotection) for this pathogen after post-transplant vaccination [ref. 23], although the lack of clear correlates of protection for pertussis had led us not to assess the immunogenicity of this valence”). Attachments Attachment Submitted filename: Response to reviewer comments - R2.docx https://doi.org/10.1371/journal.pone.0335224.r004
8 Oct 2025 Decision Letter - Ray Borrow, Editor Antibody response to tetanus, diphtheria, poliomyelitis, hepatitis B, and H. influenzae b vaccines in allogeneic hematopoietic stem cell transplant adult recipients: A multicenter trial PONE-D-25-32490R2 Dear Dr. Epaulard, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support . 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, Ray Borrow, Ph.D., FRCPath Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0335224.r005
Formally Accepted
Acceptance Letter - Ray Borrow, Editor PONE-D-25-32490R2 PLOS ONE Dear Dr. Epaulard, 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 You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days 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. 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. 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 Prof. Ray Borrow Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0335224.r006

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