PONE-D-24-35337

A Longitudinal Assessment of the Antibody Response to SARS-CoV-2 Infection in the New Mexican Population

PLOS ONE

Dear Dr. Bradfute,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we have decided that your manuscript does not meet our criteria for publication and must therefore be rejected.

I am sorry that we cannot be more positive on this occasion, but hope that you appreciate the reasons for this decision.

Kind regards,

Batool Mutar Mahdi

Academic Editor

PLOS ONE

Additional Editor Comments:

The article was well written but it is preferable to publish in your regional country

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For journal use only: PONEDEC3

PONE-D-24-35337R1A Longitudinal Assessment of the Antibody Response to SARS-CoV-2 Infection in the New Mexican PopulationPLOS ONE

Dear Dr. Bradfute,

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.

I have read the manuscript particularly carefully and I very much agree with reviewer 1 regarding the structural flaws in the manuscript; I encourage the authors to provide a comprehensive and evidence-based response and to incorporate the relevant changes and additions.

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Kind regards,

José Ramos-Castañeda, M.Sc., Ph.D

Academic Editor

PLOS ONE

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“UNM intramural grant CTSC003-11”

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Additional Editor Comments (if provided):

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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: (No Response)

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: Partly

Reviewer #2: Yes

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

Reviewer #1: No

Reviewer #2: Yes

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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

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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: This manuscript addresses the antibody response (binding, neutralizing, and ADCC) to SARS-CoV-2 infection and vaccination in a New Mexican cohort, with attention to ethnic representation. The study answers relevant questions about the duration of humoral immunity response and Fc-mediated functions post-infection and post-vaccination and adds comparisons with other viruses.

While the manuscript is based on sound scientific methods and presents results that are broadly consistent with current literature, there are several critical limitations and structural issues that must be addressed before the manuscript can be considered for publication.

Limitations by Section

1. Introduction

The introduction section inappropriately includes extensive information regarding the study methodology and main results. Specifically:

The recruitment timeline, patient demographics, and cohort description (lines 36-53).

Key results related to IgG, NAb, and ADCC findings (lines 91-110) are presented here.

Information about the circulating SARS-CoV-2 strain (Wuhan) and the study design (two blood draws) should be moved to the Materials and Methods section.

The introduction should be refocused on providing background, identifying the knowledge gap, and stating the study objective without introducing data or methods.

2. Materials and Methods

Incomplete reporting of key experimental details:

The authors mention using HEK293 cells overexpressing the Wuhan-Hu-1 S gene for ADCC assays but do not report the validation of the tecnic for the expression of the S protein (e.g., by flow cytometry or Western blot). Given the reliance on these target cells, internal validation should be either performed or referenced.

Lack of information on statistical correction:

There is no mention of adjustment for multiple comparisons (e.g., Bonferroni or FDR) despite multiple statistical tests (IgG, NAb, ADCC across groups and timepoints).

3. Results

While technically sound, the results section would benefit from a subgroup analysis based on vaccine type (Pfizer-BioNTech, Moderna, Janssen), as this could influence immune responses. This omission limits the interpretability of vaccination-related findings.

There is no mention of comorbidities in the population of the study.

The sample size in some subgroups (e.g., unvaccinated N=11, vaccinated N=14) is modest, which restricts the statistical power for detecting differences, particularly in ADCC data where variability is expected.

In the results, you grouped participants simply as "vaccinated" without distinguishing whether there were differences among those who received different types of vaccines.

The manuscript would be stronger if you mentioned that you attempted to compare vaccine types, or if you acknowledged that the sample size limited the ability to perform sub-analyses by vaccine type. This is important because each vaccine elicits distinct humoral and Fc-mediated immune responses.

4. Discussion

The discussion does not fully address some key limitations:

There is no discussion on the lack of vaccine-type stratification in the vaccinated group.

The authors acknowledge the limited cohort size in the ethnic comparison but should also emphasize how this impacts statistical power across all comparisons (e.g., antibody functional assays).

The discussion would also benefit from a clearer statement regarding the scope and applicability of the findings. For example, the authors should elaborate on how their results could be generalized (or not) to other populations or settings beyond the New Mexican cohort, and the potential relevance of these findings to current SARS-CoV-2 variants or vaccination strategies.

The discussion could also benefit from reflecting on the potential implications of using reporter cell lines (Jurkat-Lucia™ NFAT-CD16) versus primary NK cells in ADCC assays, which is relevant for interpreting effector function results.

Conclusion

This manuscript provides valuable data on immune responses to SARS-CoV-2 in a minority-majority U.S. population. However, several structural and methodological issues need to be resolved to meet the journal's standards.

Reviewer #2: The authors developed a project with the aim of evaluating the immune response, measured in various ways, of people with COVID-19 and later in the latter period, comparing those who had received the vaccine and those who had not.

The work is interesting even in the current state of COVID-19, given the various trials to evaluate the immune response, and the opportunity to observe the behavior in the first phase of vaccination.

The laboratory techniques are very well described. The statistical analysis and results are adequately presented.

Perhaps it would be helpful if the authors, if they have the information, could comment on whether their cohort used only one type of vaccine, or several, and if so, which ones were available to them at that time.

Table 2 includes an unusual column interpreting p values as non-significant. Perhaps the column with the p value could be left alone and left to each reader to interpret it.

Some journals require that the p value have only a few values after the decimal point; it is worth review it.

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Reviewer #1: No

Reviewer #2: No

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A Longitudinal Assessment of the Antibody Response to SARS-CoV-2 Infection in the New Mexican Population

PONE-D-24-35337R2

Dear Dr. Bradfute,

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.

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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,

José Ramos-Castañeda, M.Sc., Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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: (No Response)

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

Reviewer #1: Yes

Reviewer #2: (No Response)

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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: (No Response)

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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: (No Response)

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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: The authors responded appropriately to each of the observations made and provided well-supported justifications for their responses. I commend the authors for their work.

Reviewer #2: (No Response)

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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: Yes:  Irma Yvonne Amaya-Larios

Reviewer #2: No

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