PONE-D-21-12590

The metabolic hormone adiponectin modifies the association between nutritional status and pneumococcal vaccine response in vulnerable indigenous children

PLOS ONE

Dear Dr. Verhagen,

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Paolo Magni

Academic Editor

PLOS ONE

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2. Please provide the catalog numbers and sources of all kits referred to in lines 177-183.

3. Please provide the registration information for the original clinical study.

4. Please list the names of the nine indigenous Warao communities where participants were from.

5. Thank you for stating the following in the Financial Disclosure section:

[The original study was supported by Pfizer Venezuela and the Fundacion para la Investigación en Micobacterias, Caracas, Venezuela. Lilly M. Verhagen was supported by a Clinical Research Talent fellowship of the UMC Utrecht, The Netherlands.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.]. 

We note that one or more of the authors have an affiliation to the commercial funders of this research study: Pfizer Venezuela

1. Please provide an amended Funding Statement declaring this commercial affiliation, as well as a statement regarding the Role of Funders in your study. If the funding organization did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of authors' salaries and/or research materials, please review your statements relating to the author contributions, and ensure you have specifically and accurately indicated the role(s) that these authors had in your study. You can update author roles in the Author Contributions section of the online submission form.

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If your commercial affiliation did play a role in your study, please state and explain this role within your updated Funding Statement.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. 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

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

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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. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: 1) Figures 2A-2C only showed the simple regression lines of IgG levels ~ metabolic hormone levels. The data points should also be plotted with different color /shape for the three categories. The significance levels of the interaction terms in the multiple regression models should be reported here to quantitatively show whether the correlations are different between categories.

2) Table 1, it’s still unclear to me how to interpret the different superscript letters. Please be more specific.

3) Table 2, it is unclear the GMRs were between which two groups. For example, for All children category, how was GMR calculated? If it’s a ratio, what are numerator and denominator, respectively? Note that for results in Table 3, it’s clear the comparison is between under-/over-nutrition group and normal group. However, it’s unclear here.

4) Table 3, note that unadjusted GMR are the same for under- and over nutrition groups, and it’s the same as that in Table 2 (1.11, 1.06, and 1.01). Again, please clarify.

5) In the main text, GMR was interpreted as OR, which is incorrect.

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Reviewer #1: 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.

PONE-D-21-12590R1The metabolic hormone adiponectin modifies the association between nutritional status and pneumococcal vaccine response in vulnerable indigenous childrenPLOS ONE

Dear Dr. Verhagen,

Thank you for submitting your manuscript to PLOS ONE. Before formal acceptance, I invite you to address the minor points raised by Reviewer #2.

Please submit your revised manuscript by Jun 15 2022 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. 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,

Olivier Neyrolles

Section Editor

PLOS ONE

Journal Requirements:

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.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. 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: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. 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. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: All my comments have been satisfactorily addressed; there is no more comment.

All my comments have been satisfactorily addressed; there is no more comment.

Reviewer #2: This is a very interesting paper addressing a possible role of metabolic hormones and vaccine response, undertaken in a remote indigenous community.

Are there any data on invasive pneumococcal disease in the population studied or other indigenous populations? This would add to the justification for the study & would be useful to know

Minor editorial advice follows below:

Abstract

Line 40: Replace ‘which’ with ‘whom’

Lines 41-2: Replace ‘compared to’ with ‘than’

Introduction

Lines 99-100: Delete ‘described as’

Line 109: Delete ‘observed’

Lines 117-8: Delete ‘in the literature’

Lines 121-2: Replace ‘plays an important role as’ with ‘is’ and delete ‘; it is’

Lines 128-9: Replace ‘the production of adiponectin’ with ‘adiponectin production’

Line 131: Replace ‘is a hormone with’ with ‘has’

Line 137: Replace ‘compared with’ with ‘than’

Methods

Line 147: Delete ‘le’ in reachedle’

Line 191: Why is HMW Adiponectin measured rather than total levels?

Lines 193-7: This is better in the ‘Result’ section

Line 194-7: Replace ‘Values of ….’with ‘In samples with sufficient volume, leptin, adiponectin and ghrelin values were well above…’

Results

Lines 226-7: Delete ‘children’ in ‘80 stunted children, 81 normal weight children and 49 overweight children’.

Discussion

Lines 322-3: Replace ‘Another mechanism that may contribute to the mediating effect of adiponectin is related to the role of inflammasomes’ with ‘Inflammasomes may also contribute to the mediating effect of adiponectin. Inflammasomes are…’

Line 377: Replace ‘the here presented results’ with ‘Our results are specific for PCV 13 vaccination and may be different for live attenuated or inactivated vaccines’

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7. 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: 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.

The metabolic hormone adiponectin affects the correlation between nutritional status and pneumococcal vaccine response in vulnerable indigenous children

PONE-D-21-12590R2

Dear Dr. Verhagen,

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.

Again, we apologize for the delay in processing your manuscript.

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.

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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,

Olivier Neyrolles

Section Editor

PLOS ONE