Opioid-Based Haptens: Development of Immunotherapy

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is a particularly interesting review. Only just few points may be thoroughly discussed before considering publication:

• It could be of interest to expand on the opioid crisis in the introduction section in order to contextualize the place of immunotherapy;
• To the reviewer’s point of view, the part on immunoassay could be deleted; the manuscript thus solely focusing on the immunotherapy. This topic seems much more important to me;
• The authors should write a section focusing on immunotherapy against fentanyl and analogs;
• Other point: “5. Impact of opioid-based vaccination on opioid distribution”: are there data regarding distribution of other opioids (oxycodone, fentanyl, etc.)?

Comments for author File: Comments.pdf

Author Response

This is a particularly interesting review. Only just few points may be thoroughly discussed

before considering publication:

 

The authors express their gratitude to reviewer 1 for taking her/his time to review our present paper and providing us with profound comments, reflecting the expertise of the reviewer in the field of opioid research.

We have addressed our response as follows: Changes are indicated by a red color.

 

Comment 1: It could be of interest to expand on the opioid crisis in the introduction section in order

to contextualize the place of immunotherapy; To the reviewer’s point of view, the part on immunoassay could be deleted; the manuscript thus solely focusing on the immunotherapy. This topic seems much more important to me.

Response 1: The authors agree with the reviewer in this comment and appreciate the valuable suggestion. We have included in the introduction section data related to the opioid crisis. We have also deleted the immunoassay section and solely added a short background on the development of opioid haptens, which are the key chemical structure in the synthesis of opioid vaccines.

 

Comment 2. The authors should write a section focusing on immunotherapy against fentanyl and

Analogs.

Response 2: The authors agree with the reviewer, and now we have added a section related to immunotherapy against fentanyl. See section 4.3.

 

Comment 3. Other point: “5. Impact of opioid-based vaccination on opioid distribution”: are there

data regarding distribution of other opioids (oxycodone, fentanyl, etc.)?

Response 3: We thank the reviewer for this comment. Now we have added data related to the distribution of oxycodone and fentanyl next to immunization with opioid vaccines. See section 5.

 

In accordance with the changes in the text requested by the reviewer, we have also slightly modified the title.

Reviewer 2 Report

Comments and Suggestions for Authors

The work is an interesting presentation of the historical evolution of the development of potential opportunities to create a vaccine for opioid drugs.
Congratulations on your choice of topic at a much-needed time in the opioid crisis.   To sum up, the authors indicate that vaccinations are a potential solution to the epidemic of patient addiction. This is partially true because an important aspect of addiction are individual behavioral and environmental factors, therefore the aspect of a potential vaccination is important, but it is not decisive as to what should be taken into account in the work.

Next problem ist that the manuscript is a to long narrative  review, not a systematic one, which is its disadvantage. Proposes to re-edit and shorten the work and include systematic review literature in the publication.

Author Response

The work is an interesting presentation of the historical evolution of the development of potential opportunities to create a vaccine for opioid drugs. Congratulations on your choice of topic at a much-needed time in the opioid crisis.

 

The authors express their sincere gratitude to reviewer 2 for taking her/his time for reviewing our work and providing us valuable comments.

We have addressed our response as follows: Changes are indicated by a red color

 

Comment 1:  To sum up, the authors indicate that vaccinations are a potential solution to the epidemic of patient addiction. This is partially true because an important aspect of addiction are individual behavioral and environmental factors, therefore the aspect of a potential vaccination is important, but it is not decisive as to what should be taken into account in the work.

Response 1: We agree with the reviewer in that vaccines are not the sole tool to manage opioid use disorder, and the vaccine scenario is still at a preclinical level, but encouraging researchers to make more efforts is important for developing future vaccines that bring benefits for humans with OUDs. We believe that managing different factors, including those mentioned by the reviewer, along with vaccination might offer future success in the management of OUDs.

 

 

Comment 2: Next problem ist that the manuscript is a to long narrative review, not a systematic one, which is its disadvantage. Proposes to re-edit and shorten the work and include systematic review literature in the publication.

Response 2: We have deleted the immunoassay section (which was section 2) and replaced it with short on. In addition, we have added a small part related to the opioid crisis in the introduction, immunotherapy against fentanyl, and the distribution to the brain of oxycodone and fentanyl. We have added further papers.

 

In accordance with the changes in the text requested by the reviewer 1, we have also slightly modified the title.

 

We hope that these edits are as suitable as the reviewer expects.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

very interesting work! 

Reviewer 2 Report

Comments and Suggestions for Authors

Accept in present form