Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript addresses an interesting and relevant topic. The recent expansion of Oropouche virus circulation in the Americas makes this focused discussion of vaccine development particularly relevant. The emphasis on vulnerable populations distinguishes this review from prior epidemiological studies. The mansuscript is in general well-written and well-organized, however, the following major issues need to be addressed:

1. The manuscript does not describe how the literature was identified or selected. It is not clear whether it is a narrative review, scoping review or systematic review. Please add a brief paragraph specifying the type of review, indicate databases searched, approximate timeframe and selection criteria, and clarify the source of epidemiological data.
2. Please check, there is substantial overlap between: section 4 (vulnerable populations), section 6 (vaccine development challenges) and section 8 (platform suitability) and the Conclusion. Key ideas are repeated multiple times, such as population-centered vaccine design and the need for non-replicating platforms in high-risk groups. Please incorporate all vaccine platform discussion into a single section and shorten the implementation framework (section 7) to avoid policy-level generalities. Conclusions are too long and should be more concise.
3. Several recommendations regarding vaccine platform suitability are largely extrapolated from other viral vaccines rather than supported by OROV-specific clinical data. Please state where conclusions are based on analogy rather than direct OROV-data and use more cautious language regarding recommendation of specific platforms. It would be good to add a brief paragraph clarifying current evidence gaps.
4. The manuscript strongly supports vaccine development but does not sufficiently examine competing public health priorities. Since OROV is typically self-limiting and mortality is low, the rationale for large-scale vaccine investment should therefore be discussed more critically.
5. Please clarify epidemiological Tables 2 and 3. Add a legend explaining symbols and categories, regarding reporting format (are the numbers annual or cumulative?), what constitutes a confirmed case (diagnosis?). Please ensure that each Table references its source of data.

Comments on the Quality of English Language

Minor English editing is needed.

Author Response

Comments and Suggestions for Authors

This manuscript addresses an interesting and relevant topic. The recent expansion of Oropouche virus circulation in the Americas makes this focused discussion of vaccine development particularly relevant. The emphasis on vulnerable populations distinguishes this review from prior epidemiological studies. The mansuscript is in general well-written and well-organized, however, the following major issues need to be addressed:

Response: We thank the reviewer for their positive assessment of our manuscript and for recognizing the relevance and timeliness of our work. We appreciate their thoughtful feedback and have addressed the major issues below.

1. The manuscript does not describe how the literature was identified or selected. It is not clear whether it is a narrative review, scoping review or systematic review. Please add a brief paragraph specifying the type of review, indicate databases searched, approximate timeframe and selection criteria, and clarify the source of epidemiological data.

Response: Thank you for this helpful suggestion. We agree and have added a paragraph at the end of the Introduction clarifying that this study is a narrative review. The revised text now specifies the databases searched (PubMed and Scopus), the timeframe for the included literature (1961–2026), the general selection criteria, and the sources of epidemiological data (WHO, PAHO, and Brazilian national surveillance reports). The change can be found on Page 3, Introduction, final paragraph.

2. Please check, there is substantial overlap between: section 4 (vulnerable populations), section 6 (vaccine development challenges) and section 8 (platform suitability) and the Conclusion. Key ideas are repeated multiple times, such as population-centered vaccine design and the need for non-replicating platforms in high-risk groups. Please incorporate all vaccine platform discussion into a single section and shorten the implementation framework (section 7) to avoid policy-level generalities. Conclusions are too long and should be more concise.

Response: We thank the reviewer for this suggestion. The manuscript has been revised to reduce overlap among Sections 4, 6, 8, and the Conclusion. Discussion of vaccine platforms has now been consolidated in Section 8, while Sections 6 and 7 focus on general scientific challenges and implementation considerations, respectively. These revisions clarify the structure and reduce redundancy across the manuscript.

3. Several recommendations regarding vaccine platform suitability are largely extrapolated from other viral vaccines rather than supported by OROV-specific clinical data. Please state where conclusions are based on analogy rather than direct OROV-data and use more cautious language regarding recommendation of specific platforms. It would be good to add a brief paragraph clarifying current evidence gaps.

Response: We thank the reviewer for this important comment. The manuscript has been revised to clarify that conclusions regarding vaccine platform suitability are based on analogy to other viral vaccines rather than on OROV-specific clinical evidence. The language throughout Section 8 has been adjusted to adopt a more cautious tone when discussing potential platforms. In addition, a short paragraph outlining current evidence gaps and the early stage of OROV vaccine development has been added to highlight the limited availability of OROV-specific data.

4. The manuscript strongly supports vaccine development but does not sufficiently examine competing public health priorities. Since OROV is typically self-limiting and mortality is low, the rationale for large-scale vaccine investment should therefore be discussed more critically.

Response: We thank the reviewer for raising this important point. We acknowledge that OROV infection is generally self-limiting and that vaccine development should be considered alongside other public health priorities. A brief discussion has been added in Section 7 to note that decisions regarding large-scale vaccination would likely require careful evaluation of cost-effectiveness and competing interventions. As the primary focus of this review is the scientific and technological aspects of vaccine development rather than detailed policy comparisons, this aspect is discussed only briefly.

5. Please clarify epidemiological Tables 2 and 3. Add a legend explaining symbols and categories, regarding reporting format (are the numbers annual or cumulative?), what constitutes a confirmed case (diagnosis?). Please ensure that each Table references its source of data.

Response: We thank the reviewer for this helpful suggestion. The legends of Tables 2 and 3 have been expanded to clarify epidemiological categories and symbols. We have also specified the reporting format of case numbers and added a brief definition of confirmed cases. In addition, the data sources for both tables are now indicated in the table notes, with references to PAHO/WHO epidemiological updates.

Comments on the Quality of English Language

Minor English editing is needed.

Response: Thank you for your suggestion. To address this, we have thoroughly revised the manuscript to improve the English language. Furthermore, we used ChatGPT (GPT-5, OpenAI) to assist with language editing and enhance the text's clarity and readability. All changes have been reviewed and approved by the authors.

Reviewer 2 Report

Comments and Suggestions for Authors

The review article “Oropouche Virus (OROV) Vaccine Development for Vulnerable Populations: Epidemiological Context, Challenges and Future Directions” attempts to summarize the current status of viral epidemiology and transmission, their clinical implications, and the present and future prospects for vaccine development. While the topic is timely and potentially impactful, the manuscript lacks focus and depth.

The first half of the article (up to Section 4) maintains a reasonable level of structure and thematic direction. However, from Section 4 onward, the narrative becomes diffuse and unfocused, making it difficult to identify a clear central message or critical synthesis of the literature. Rather than providing pointed analysis of key studies, the manuscript remains broad and descriptive, which weakens its scholarly impact. To meaningfully engage readers and meet the standards expected of a high-quality review, substantial revision is required. The authors should refine the scope, sharpen the central thesis, critically evaluate landmark and recent studies, and ensure thematic continuity throughout the later sections. Without significant restructuring and tightening of the narrative, the manuscript does not fully realize its potential.

Major concerns

Table 1: The table is currently too wordy. The Phase column and the Keywords/Themes column largely overlap in content. Similarly, the Defining Features and Qualitative Description columns convey similar information. Consider merging overlapping columns. Convert the Qualitative Description column into concise bullet points. Avoid full sentences—use short phrases only.

Tables 2 and 3: Explore ways to merge Tables 2 and 3, as they appear conceptually related and may be streamlined into a single, more cohesive table.

Lines 101–109: It is unclear whether this section is intended as part of the main text or a figure legend. The content is well-suited for a figure legend and may be better placed there.

Transmission Dynamics: It would be advisable to include a clear and well-designed schematic illustrating transmission dynamics to improve conceptual clarity.

Table 4: this largely repeats information already described in the text and does not provide additional insights. It may therefore be omitted unless new information is added.

Section 4 needs to be concise.

Current Landscape of Therapeutics and Vaccines: This section requires substantially more depth and scientific rigor. Given the rapid advancements in this area, there is significant scope to expand the discussion with detailed mechanistic insights. Readers are particularly interested in the therapeutic and vaccine landscape; therefore, this section should provide a critical and comprehensive synthesis rather than a brief overview. Strengthening this part of the manuscript would greatly enhance its impact and relevance.

Instead of titling the section “Challenges in OROV Vaccine Development for Vulnerable Populations,” it would be more appropriate to broaden the scope and present it as “Challenges in OROV Vaccine Development.”

The remaining Sections 7 and 8 should also be revised to enhance scientific rigor and precision. The discussion currently reads as generalized and descriptive

Comments on the Quality of English Language

As mentioned above, the manuscript requires substantial revision to enhance its scientific depth and analytical rigor. While the language is generally acceptable, the discussion remains overly broad and descriptive.

Author Response

Comments and Suggestions for Authors

The review article “Oropouche Virus (OROV) Vaccine Development for Vulnerable Populations: Epidemiological Context, Challenges and Future Directions” attempts to summarize the current status of viral epidemiology and transmission, their clinical implications, and the present and future prospects for vaccine development. While the topic is timely and potentially impactful, the manuscript lacks focus and depth.

The first half of the article (up to Section 4) maintains a reasonable level of structure and thematic direction. However, from Section 4 onward, the narrative becomes diffuse and unfocused, making it difficult to identify a clear central message or critical synthesis of the literature. Rather than providing pointed analysis of key studies, the manuscript remains broad and descriptive, which weakens its scholarly impact. To meaningfully engage readers and meet the standards expected of a high-quality review, substantial revision is required. The authors should refine the scope, sharpen the central thesis, critically evaluate landmark and recent studies, and ensure thematic continuity throughout the later sections. Without significant restructuring and tightening of the narrative, the manuscript does not fully realize its potential.

Response: We thank the reviewer for their positive assessment of our manuscript and for recognizing the relevance and timeliness of our work. We appreciate this comment and have revised the latter sections to improve thematic focus and analytical depth, particularly by restructuring Sections 6–8 and reducing the length of descriptive passages.

Major concerns

1. Table 1: The table is currently too wordy. The Phase column and the Keywords/Themes column largely overlap in content. Similarly, the Defining Features and Qualitative Description columns convey similar information. Consider merging overlapping columns. Convert the Qualitative Description column into concise bullet points. Avoid full sentences—use short phrases only.

Response: Thank you for the suggestion. Table 1 has been revised to reduce redundancy. The overlapping columns (“Keywords/Themes” and “Defining Features”) were merged into a single Key Events / Features column, and the former Qualitative Description entries were rewritten as concise bullet-point phrases instead of full sentences. The revised table now includes five columns (Phase, Time Period, Key Events/Features, Quantitative Data, and Geographic Range), resulting in a shorter, clearer presentation.

2. Tables 2 and 3: Explore ways to merge Tables 2 and 3, as they appear conceptually related and may be streamlined into a single, more cohesive table.

Response: Thank you for the suggestion. Tables 2 and 3 have been merged into a single table presenting epidemiological data for both 2024 and 2025. Parallel columns are now provided for epidemiological status, confirmed cases, deaths, and transmission patterns for each year, allowing direct comparison while reducing redundancy and improving clarity.

3. Lines 101–109: It is unclear whether this section is intended as part of the main text or a figure legend. The content is well-suited for a figure legend and may be better placed there.

Response: Thank you for pointing this out. Lines 101–109 are intended to be the figure legend for Figure 1, rather than part of the main text. The current placement resulted from a formatting issue in the manuscript layout. In the revised version, this section has been moved and clearly formatted as the Figure 1 legend to avoid confusion.

4. Transmission Dynamics: It would be advisable to include a clear and well-designed schematic illustrating transmission dynamics to improve conceptual clarity.

Response: Thank you for this helpful suggestion. A schematic illustrating the transmission dynamics of Oropouche virus has now been added to improve conceptual clarity. The figure summarizes both the sylvatic and urban cycles, including human–vector–human transmission. This schematic is now presented as Figure 2 and referenced in the corresponding section of the manuscript.

5. Table 4: this largely repeats information already described in the text and does not provide additional insights. It may therefore be omitted unless new information is added.

Response: Thank you for this helpful comment. The table previously presented as Table 4 has been renumbered as Table 3 in the revised manuscript. We have retained this table because it helps clarify the characteristics of vulnerable populations discussed in the text and provides a concise overview for readers. In response to the reviewer’s suggestion, the table has been revised and simplified to reduce redundancy and to minimize overlap with the main text.

6. Section 4 needs to be concise.

Response: Thank you for this helpful comment. Section 4 has been revised and shortened to improve conciseness. The content has been streamlined to focus on the key characteristics of vulnerable populations, and redundant descriptions have been removed.

7. Current Landscape of Therapeutics and Vaccines: This section requires substantially more depth and scientific rigor. Given the rapid advancements in this area, there is significant scope to expand the discussion with detailed mechanistic insights. Readers are particularly interested in the therapeutic and vaccine landscape; therefore, this section should provide a critical and comprehensive synthesis rather than a brief overview. Strengthening this part of the manuscript would greatly enhance its impact and relevance.

Response: Thank you for this valuable suggestion. Given the currently limited data on OROV-specific therapeutics and vaccines, we have expanded the analysis by drawing on insights from vaccine development for other arboviral diseases. To improve clarity and focus, the revised section now discusses vaccine considerations separately for different vulnerable populations and more clearly outlines the current status of vaccine development. These revisions aim to provide a more structured and informative overview of the therapeutic and vaccine landscape.

8. Instead of titling the section “Challenges in OROV Vaccine Development for Vulnerable Populations,” it would be more appropriate to broaden the scope and present it as “Challenges in OROV Vaccine Development.”

Response: Thank you for this helpful suggestion. While the first part of this section introduces the general background of challenges in OROV vaccine development, the latter part of the discussion focuses primarily on vaccine platform considerations for vulnerable populations. For this reason, we have retained the original section title. However, in response to the reviewer’s comment, the structure of the latter sections, particularly Section 8, has been revised to more clearly emphasize the discussion of vaccine platform suitability for vulnerable populations.

9. The remaining Sections 7 and 8 should also be revised to enhance scientific rigor and precision. The discussion currently reads as generalized and descriptive

Response: Thank you for this helpful comment. Sections 7 and 8 have been revised to improve scientific rigor and precision. In particular, Section 7 has been shortened and refocused on implementation considerations, while Section 8 now provides a more structured discussion of vaccine platform suitability across vulnerable populations.

Comments on the Quality of English Language

As mentioned above, the manuscript requires substantial revision to enhance its scientific depth and analytical rigor. While the language is generally acceptable, the discussion remains overly broad and descriptive.

Response: Thank you for your suggestion. To address this, we have thoroughly revised the manuscript to improve the English language. Furthermore, we used ChatGPT (GPT-5, OpenAI) to assist with language editing and enhance the text's clarity and readability. All changes have been reviewed and approved by the authors.

Reviewer 3 Report

Comments and Suggestions for Authors

The authors reported on the development of the Oropouche Virus (OROV) vaccine and their epidemiological context. However, this reviewer realised that aspects of vaccine development were somewhat secondary in this manuscript and not highlighted as a priority, as claimed by the article title. Can the authors somehow edit the title to eliminate this bias? My further comments are listed below: 

1. The reference style and in-text references do not match the journal's citation style.
2. L 49-50: "The earliest recognized human outbreak occurred in 1961 in the Amazon region of Brazil". Citation is missing. 
3. Tables 2 and 3 require citations.
4.  Why does Figure 1 compare only between two particular years, 2024 and 2025?
5. One major weakness of this review is the lack of descriptions of the article search, inclusion, and exclusion criteria. Please describe these aspects in detail: unbiased selection of the literature used for data synthesis.

Author Response

Comments and Suggestions for Authors

The authors reported on the development of the Oropouche Virus (OROV) vaccine and their epidemiological context. However, this reviewer realised that aspects of vaccine development were somewhat secondary in this manuscript and not highlighted as a priority, as claimed by the article title. Can the authors somehow edit the title to eliminate this bias? My further comments are listed below:

Response: Thank you for this helpful comment. We agree that the emphasis on vaccine development could be clarified. In the revised manuscript, we have adjusted the structure and wording in the Introduction and later sections to more clearly highlight vaccine development as the central theme of the review, while maintaining the epidemiological and public health context necessary to frame the discussion.

1. The reference style and in-text references do not match the journal’s citation style.

Response: Thank you for pointing this out. The reference list and in-text citations have now been revised and formatted in accordance with the MDPI reference style.

2. L 49-50: “The earliest recognized human outbreak occurred in 1961 in the Amazon region of Brazil”. Citation is missing.

Response: Thank you for pointing this out. The appropriate citation has now been added to support this statement in the revised manuscript.

3. Tables 2 and 3 require citations.

Response: Thank you for this helpful comment. Source information has been added to the table. In the revised manuscript, the former Tables 2 and 3 have been merged into Table 2, and the table now indicates that the data were compiled from PAHO and WHO epidemiological situation reports and updates on Oropouche virus in the Americas, with 2025 data based on reports available up to 13 August 2025.

4. Why does Figure 1 compare only between two particular years, 2024 and 2025?

Response: Thank you for this helpful comment. Figure 1 focuses on 2024 and 2025 because these years correspond to the recent re-emergence and expansion of OROV transmission in the Americas, during which a substantial increase in reported cases was observed. The comparison between these two years was therefore intended to highlight the most recent epidemiological developments and the geographic spread of OROV.

5. One major weakness of this review is the lack of descriptions of the article search, inclusion, and exclusion criteria. Please describe these aspects in detail: unbiased selection of the literature used for data synthesis.

Response: Thank you for this helpful comment. This study is a narrative review. The revised text now specifies the databases searched (PubMed and Scopus), the timeframe for the included literature (1961–2026), the general selection criteria, and the sources of epidemiological data (WHO, PAHO, and Brazilian national surveillance reports). This information has been added to the final paragraph of the Introduction (Page 3).

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you for addressing all comments.

Comments on the Quality of English Language

English language is fine.

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for addressing the major concerns. The manuscript now appears more streamlined and focused.

Reviewer 3 Report

Comments and Suggestions for Authors

Thanks for considering my previous comments.