Tuberculosis Vaccines: An Update of Recent and Ongoing Clinical Trials
Round 1
Reviewer 1 Report
The authors have tried to review the new TB vaccines in development recently. They have selected the new TB vaccines under clinical trials and categorized them according to vaccine type and reviewed each candidate. Finally, they drew a conclusion that the use of nanovaccines could be a promising option for new TB vaccines.
The manuscript looks well organized and well written.
Major points;
The authors mention that one of the main objectives of this manuscript is the use of nanovaccines as a novel TB vaccine, so they gave a lot of space to describe it in “Discussion” and in “Conclusion”. But I think they need to include the paragraph about nanovaccine in the main text about what it is, the actual use of nanovaccine in other domine, the strong points and the weak points, why it is important as TB vaccine considering its pathogenesis, the efficacy including ID9+GLA-SE and RUTI, etc etc.
The “Conclusion” doesn’t look so clear why nanovaccine is promising in the future in TB, high efficacy, high safety, low cost, etc ?
Author Response
We thank the Reviewer for your suggestions. In accordance, within the introduction we added a paragraph where we aim to demonstrate the use of nanovaccines in other areas, highlighting the strengths of nanovaccines in TB prevention. Their weaknesses have also been discussed. In addition, the conclusion has been clarified to better emphasise the promising nature of nanovaccines in TB. The changes made in our article were highlighted in the revised manuscript by using the track changes mode in MS word.
Reviewer 2 Report
The review from Saramago and coleagues is a braod paper that covers a large area of scientific work on new tuberculosis vaccines.
The intorduction provides initial informations and is complete. Further the authors describe the methods and finaly report the newest informations about discaveries in the field. I am sure that the paper is worth of considering to publish.
Author Response
We would like to thank the Reviewer for the time you have dedicated to read the manuscript, and for your positive comment.
Reviewer 3 Report
I have revised the review paper by Saramago et al. on new TB vaccines.
The paper should be focused on vaccines, so the extensive Introduction on TB pathogenesis seems unnecessarily long.
The long paragraph on the history of TB (from line 66-90 is totally unnecessary.
The keyword strategy seems insufficient, lacking terms such as “immunization” or “vaccination”. And do not include new modification to BCG.
In light of recent reviews on the topic (such as Fatima et al. Life Sciences 2020, and Kaufmann Front Immunol 2020) this contribution does not appear to be urgently needed.
Furthermore, the authors claim that the main objective was to “highlight the progress in the development of new TB vaccines” which is not true, as they restrict the review to vaccines that are already in the clinical trial stage. To this, the title “from development to clinical trial” is also inaccurate.
The whole extensive description of the different types of vaccine, is written in a very “arid” way, with excess of details, and without any clear take home message.
On the other hand, I was perplexed that when the DNA vaccines turn came (section 3.5), they only afforded a single short paragraph to these.
To make things even odder, section 3.5 is followed by 3.4.1
Author Response
The Manuscript ID applsci-1340019, entitled “New tuberculosis vaccines from discovery to clinical trials”, was carefully rewritten to address all the concerns and suggestions raised by the Reviewer. A detailed explanation of the improvements made is described below. The changes made to the text were highlighted in the revised manuscript by using the track changes mode in MS word. We believe that the current improved version of our manuscript is appropriate for publication.
Comment 1: “The paper should be focused on vaccines, so the extensive Introduction on TB pathogenesis seems unnecessarily long.”
Author response: Considering that TB is a global health problem of overwhelming proportions, we found interesting to describe TB pathogenesis in detail. However, we are in full agreement with the reviewer and therefore this specific part was shortened.
Alterations: Please check in the main document.
The list of References was updated accordingly.
Comment 2: “The long paragraph on the history of TB (from line 66-90 is totally unnecessary.”
Author response: We acknowledge and are in full agreement with the referee and therefore this description was shortened.
Alterations: Please check in the main document.
The list of References was updated accordingly.
Comment 3: “The keyword strategy seems insufficient, lacking terms such as “immunization” or “vaccination”. And do not include new modification to BCG.”
Author response: We agree with the Reviewer, and we are grateful for the keywords suggestion. Accordingly, a new search was performed using these keywords in the other terms category. As you may see in the revised manuscript, 4 new clinical trials were found. One of them was excluded since it does not follow the inclusion criteria. The other 3 studies were selected for review, and their results were discussed in the respective vaccine type category.
Figure 2 and Table 1 were modified. The list of References was updated accordingly.
Comment 4: “In light of recent reviews on the topic (such as Fatima et al. Life Sciences 2020, and Kaufmann Front Immunol 2020) this contribution does not appear to be urgently needed.”
Author response: We understand the Reviewer’s concern. Indeed, Fatima et al. Life Sciences 2020 is a very interesting review that discusses the history of BCG and summarizes the recent advances in improving BCG immunization along with other new vaccines in clinical trials. Regarding Kaufmann Front Immunol 2020, this review is focused on how immunology serves for a rational design of TB vaccines. Both reviews discuss novel vaccine candidates in clinical trials, but they do not include a detailed information of each clinical trial. Accordingly, the novelty of our manuscript resides on the fact that the recent and ongoing clinical trials on TB vaccines were critically analysed and information regarding their study design, eligibility criteria, outcome measures and main results was gathered and organized.
Comment 5: “Furthermore, the authors claim that the main objective was to “highlight the progress in the development of new TB vaccines” which is not true, as they restrict the review to vaccines that are already in the clinical trial stage. To this, the title “from development to clinical trial” is also inaccurate.”
Author response: We agree with the Reviewer, thus the title of the manuscript was modified to “Tuberculosis vaccines: an update of recent and ongoing clinical trials”.
Comment 6: “The whole extensive description of the different types of vaccine, is written in a very “arid” way, with excess of details, and without any clear take home message.”
Author response: We understand the referee’s concern. The main goal of this review was to detail and critically discuss the ongoing clinical trials on TB vaccines. For each type of vaccine, the trials were analysed and information regarding their study design, eligibility criteria, outcome measures and main results was gathered and organized. Regarding the referee’s suggestion, the manuscript was fully revised, and the information was discussed in a more critical perspective in order to allow the reader to obtain some clear take home message.
Alterations: Please check in the main document.
Comment 7: “On the other hand, I was perplexed that when the DNA vaccines turn came (section 3.5), they only afforded a single short paragraph to these.
Author response: We understand the referee’s concern. However, there is only one clinical trial involving DNA vaccines for TB prevention or treatment and therefore the information is limited. Moreover, the only trial was withdrawn, and no participants were enrolled. Therefore, besides the description of the study design and eligibility criteria, no outcome measures or main results are available. Since we are in full agreement with the referee’s that this thematic is of major importance, new information on the advantages and disadvantages of DNA vaccines was added to this section.
Comment 8: “To make things even odder, section 3.5 is followed by 3.4.1”
Author response: Thank you for paying attention to this mistake. The sub-section number was corrected accordingly.
Finally, we would like to thank for the valuable comments and suggestions, which helped us to improve the quality of the manuscript, making it more understandable and clearer.
Round 2
Reviewer 1 Report
no comments.
