Evolution of Tick Vaccinology Highlights Changes in Paradigms in This Research Area

Round 1

Reviewer 1 Report

 

The manuscript titled: “Evolution of tick vaccinology highlights changes in paradigms 2 in this research area.” submitted to the journal Vaccines with manuscript ID: vaccines-2107033 by Agustín Estrada-Peña and José de la Fuente is a commentary on the basis of 274 documents from 94 sources in a period of 1991-2022. The authors pointed out the gaps in the need for collaborations with countries in Africa and Asia facing problems with ticks and tick-borne diseases.

Although the paper is well written and presents a wide range of research filed in a period of 31 years, I have serious doubts about the fitting of the journal’s aim and scope.  

In addition, some of my specific major concerns are:

1) What is the exact type of the paper – commentary or research article? The structure of the paper should follow the instruction for the specific type of paper.

2) The paper includes studies on the resistance to tick infestation and others on the vaccines for tick-borne pathogens without discussion of the immunopathological mechanism. The challenges of the development of effective anti-tick and transmission-blocking vaccines should also be discussed.

3) The text labels in the Figures 1-6 are hard to read.

 

 

Author Response

Reviewer #1

The manuscript titled: “Evolution of tick vaccinology highlights changes in paradigms 2 in this research area.” submitted to the journal Vaccines with manuscript ID: vaccines-2107033 by Agustín Estrada-Peña and José de la Fuente is a commentary on the basis of 274 documents from 94 sources in a period of 1991-2022. The authors pointed out the gaps in the need for collaborations with countries in Africa and Asia facing problems with ticks and tick-borne diseases.

Although the paper is well written and presents a wide range of research filed in a period of 31 years, I have serious doubts about the fitting of the journal’s aim and scope. 

In addition, some of my specific major concerns are:

1) What is the exact type of the paper – commentary or research article? The structure of the paper should follow the instruction for the specific type of paper.

2) The paper includes studies on the resistance to tick infestation and others on the vaccines for tick-borne pathogens without discussion of the immunopathological mechanism. The challenges of the development of effective anti-tick and transmission-blocking vaccines should also be discussed.

3) The text labels in the Figures 1-6 are hard to read.

 

Dear Reviewer,

Many thanks for your comments on our manuscript. We consider that all your questions point to the same address, and we did choose to reply all of them together. We do not have questions regarding the validity of the manuscript for the Journal since the Editor(s) did no comments at the submission. In any case, we acknowledge this will be the decision of the Editor after resubmission, We modestly think that the paper has a place in the Journal because it is only a short commentary on a narrow field and using some well-known methods…that have been never applied before to obtain these conclusions.

Regarding your questions, I think we did not manage to transmit clearly the message of what this manuscript intends: a short scientometrics study about the “pros and cons” of the advances in the field, how the experts on the topic have been moving in circles with occasional changes of paradigm, and where the field needs considerable improvement. Thus, we modified several key sentences at the beginning of the manuscript to left clear what is the purpose of the study.

This includes an important question: this manuscript is not a review about “mechanisms of transmission”, “challenges” or “development of transmission-blocking vaccines”. This is a kind of bibliographical analysis to reveal hidden relationships among the manuscripts published on the topic. Excellent revisions exist on the topics proposed by the Reviewer, to whom we warmly acknowledge for the suggestion, but are far of the purpose of our study.

Regarding the point #3 in your comments, please note that this is the standard output of the used software and there is no way to modify it (we did test it). In any case, please note that manuscript is published only and that the final charts are high resolution ones. Nothing prevents the readers to increase the on screen zoom to improve the readability.

Reviewer 2 Report

This is an interesting commentary piece that utilized analysis of publications related to tick vaccination development to explore topics of interest, collaborative networks, and location of work within the field over time.  The conclusions are quite important, and highlight the need for both wider collaborative networks involving scientists in countries that are actually affected by tick-borne diseases of livestock, and for implementation of strategies within those countries.

Information beginning in line 295 should be moved to a separate section focused on proposed changes.  Inclusion of more proposed solutions (or perhaps discussion of examples of solutions utilized in related fields -- e.g. neglected tropical diseases) would make this work more useful to readers and would better inform funding agencies (who largely limit scope of work, collaborative potential, and implementation of new strategies in "neglected countries").

Line 223, "Kenia" should be changed to Kenya

Author Response

Reviewer #2

 

This is an interesting commentary piece that utilized analysis of publications related to tick vaccination development to explore topics of interest, collaborative networks, and location of work within the field over time.  The conclusions are quite important, and highlight the need for both wider collaborative networks involving scientists in countries that are actually affected by tick-borne diseases of livestock, and for implementation of strategies within those countries.

 

Information beginning in line 295 should be moved to a separate section focused on proposed changes.  Inclusion of more proposed solutions (or perhaps discussion of examples of solutions utilized in related fields -- e.g. neglected tropical diseases) would make this work more useful to readers and would better inform funding agencies (who largely limit scope of work, collaborative potential, and implementation of new strategies in "neglected countries").

 

Many thanks for your comments. We think your last set of sentences are quite important for the context of this manuscript. We did our best to incorporate these comments about related fields (e.g., “neglected diseases”) trying to improve our message regarding a wider international collaboration, a better founding, and a coordinated effort. Perhaps the “coordinated effort” (that would require a considerable funding) is the most important message here.

 

Line 223, "Kenia" should be changed to Kenya

Changed. Many thanks for catching the typo.

Reviewer 3 Report

The manuscript entitled 'Evolution of tick vaccinology highlights changes in paradigms in this research area' appears to cover an analysis of publications associated with key words 'Bm96, ankirin, subolesin' as tick vaccine candidates and also TBD key words. Would have the use of these terms skewed the analysis? rather than just using 'vaccine' or 'antigen' to be more general. The title could be more specific as the review does not really cover evolution of 'tick vaccinology' with a keyword focus on Bm86/subolesin/TBDs ? The paper undertakes a publication analysis not only on topic but citations, author origins etc.

The 'evolution' is from 1991? yet the gut protein tick vaccine idea was developed in 1979. Not sure why 1991 was chosen as the start date. Please elaborate.

This reviewer is not familiar with the methodology used. I am familiar with using Covidence for systematic reviews using key words across 6-8 databases. This approach does appear to have more depth than the use of systemic review methods. I request that the authors justify the methodology chosen either in the introduction or results/discussion section. There are some references cited - but please elaborate. 

Author Response

Reviewer #3

 

The manuscript entitled 'Evolution of tick vaccinology highlights changes in paradigms in this research area' appears to cover an analysis of publications associated with key words 'Bm96, ankirin, subolesin' as tick vaccine candidates and also TBD key words. Would have the use of these terms skewed the analysis? rather than just using 'vaccine' or 'antigen' to be more general. The title could be more specific as the review does not really cover evolution of 'tick vaccinology' with a keyword focus on Bm86/subolesin/TBDs ? The paper undertakes a publication analysis not only on topic but citations, author origins etc.

Many thanks for your comments. The search using more generalist terms was done and produced near 36,000 publications. This high number of publications turned the analysis unfeasible, not only in terms of raw analysis, but in terms of computation times (weeks !!!) and the almost complete impossibility to correctly address the conclusions. We did also anther search including topics related to pathogens (either in humans or animals) resulting in a similar dilemma. The search for terms of vaccines anti tick-transmitted pathogens in humans (i.e., anti-ospA for Borrelia spp.) produced an artificial separation of the clustering of references. All the references regarding anti-tick vaccines related to animal health were in a cluster, and all the references regarding anti-tick vaccines related to human health were in a different cluster. We wanted to have a solid “corpus” of research on which obtain conclusions. This study is more related to the “trends” in a small field of anti-tick vaccines than on the immense and many times unrelated references regarding all the vaccines ever assayed against ticks or pathogens. We did a final test before to obtain the final one on which this manuscript was built: the inclusion of names of pathogens and vaccines. Such search resulted again in a complete disconnection of the published papers. Of course, all these results were of interest, but it was necessary to fit our findings into a relatively short piece of text and we decided to focus on the terms for search as stated in the manuscript.

Making long history short, we wanted to focus only on animal health, tick control (which aims also to block the transmission of pathogens) but not on the many vaccines that have been assayed in the wet lab, but only a few have been marketed. This procedure ensured a solid background and tractable results.

 

The 'evolution' is from 1991? yet the gut protein tick vaccine idea was developed in 1979. Not sure why 1991 was chosen as the start date. Please elaborate.

Since this manuscript account with the co-authorship and citations, it is necessary that the dataset used has all these links available. The PubMed library has these crossed references (i.e., doi of each manuscript, cited references linked to other manuscripts, etc.) available only since the year 1991. For other papers published before the date, the presence of such information is intermittent and less elaborated. Since we wanted to use data available in three repositories, they must be homogeneous.

 

This reviewer is not familiar with the methodology used. I am familiar with using Covidence for systematic reviews using key words across 6-8 databases. This approach does appear to have more depth than the use of systemic review methods. I request that the authors justify the methodology chosen either in the introduction or results/discussion section. There are some references cited - but please elaborate.

Many thanks regarding this comment. Sometimes, it is difficult to find the balanced point in which an adequate and short explanation of terminology and methods is used, with a few references for the interested readers. We agree that the topic may be very different for many readers interested on the topic. Therefore, we included more details in the explanation of the methodology (with the adequate references). Details about methodology are available in Methods.

Round 2

Reviewer 1 Report

Thank you for the opportunity to review the manuscript titled: “Evolution of tick vaccinology highlights changes in paradigms in this research area.” submitted to the journal Vaccines with manuscript ID: vaccines-2107033

Authors improve the paper in a significant rate and the aim is clarified. I accept the revised version of the paper but still have serious doubts about the fitting of the journal’s aim and scope. However, the paper is well written and presents a wide range of research in the period of 1991-2022 and highlight new directions to advance in development of effective vaccines for the control of tick infestations and tick-borne pathogens.

Respectively, if the Editors find the paper as suitable for publication in the journal Vaccine, fitting to the journal scope I will be happy to support the publishing of the manuscript.

Sincerely yours,