PONE-D-21-01240

Is Vaccination a Viable Method to Control Johne’s Disease Caused by Mycobacterium avium subsp. paratuberculosis? Data from 12 Million Ovine Vaccinations and 7.6 Million Carcass Examinations in New South Wales, Australia from 1999-2009

PLOS ONE

Dear Dr. Links,

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PLOS ONE

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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: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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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: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Paratuberculosis is a major disease problem the world over affecting ruminant livestock. Efforts to control paratuberculosis have been impeded a lack of understanding of the immune response to the different lineages of the pathogen M. a. Paratuberculosis, the inability to detect infected animals, especially at the early stages of infection and the lack of a vaccine that elicits sterile immunity. The authors have prepared a comprehensive review, based on observational information, describing the evolution of a program to control an outbreak of ovine paratuberculosis in sheep in Australia that started in the in the late 1970s. The events in Australia paralleled the emergence of paratuberculosis becoming a major disease problem in other countries. It is difficult to summarize and highlight the events that led to the development of a successful voluntary program to control paratuberculosis, based on the use of a killed vaccine. However, they have succeeded in developing an informative review highlighting the events that led to a successful outcome. A study in Spain pointed to the value of using a killed vaccine for its therapeutic and prophylactic potential. Initial studies demonstrated vaccination of whole dairy herds endemically infected with a killed vaccine reduced the incidence animals progressing to the clinical stage of disease. Success of trial studies showing the efficacy of vaccination led to gradual acceptance of a killed vaccine strategy to bring paratuberculosis under control. Lessons learned through implementation of the vaccination program, as described, are a major contribution of the review. Paratuberculosis remains a threat because the killed vaccine controls but does not clear infection. Demonstration of success provides points to the potential of using a killed vaccine as a first step in controlling paratuberculosis in livestock at the international level.

Reviewer #2: 1. Although there is no restriction on word count, the manuscript should be presented in a reader-friendly way by which is not containing too much detail. For example, in Methods, the vaccination procedures, financial assistance, producer workshops, feedback to producers, and sheep breeds affected can be briefly stated in manuscript then attach the full information as supplementary data if needed. Word deduction is also needed in Discussion section. I understand that authors want to discuss every situation and factor which may lead to the results, but the discussion pattern should be tightly connected to the significance findings in this study with more concise descriptions.

2. In this study, most of the analysis were calculated based on the number of sheep, so the authors might consider moving table 1 and table 3 to supplementary data.

3. Is MAP 316F the dominant strain in Australia sheep suffering from OJD? Is there any cross protection between the vaccine and other MAP strains that might also exist in Australia ruminant flocks?

4. The authors may use statistical analysis to elucidate the correlation among OJD, vaccine doses, and herd immunity.

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Reviewer #1: Yes: William C. Davis

Reviewer #2: No

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Is Vaccination a Viable Method to Control Johne’s Disease Caused by Mycobacterium avium subsp. paratuberculosis? Data from 12 Million Ovine Vaccinations and 7.6 Million Carcass Examinations in New South Wales, Australia from 1999-2009

PONE-D-21-01240R1

Dear Dr. Links,

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.

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Kind regards,

Yung-Fu Chang

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: Yes

**********

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

Reviewer #1: N/A

Reviewer #2: N/A

**********

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

**********

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: The authors have responded to suggestions that improved presentation and conclusions of the rather extensive presentation of findings.

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: William C. Davis, PhD

Reviewer #2: No