A Tiered Vaccine Framework: Prioritizing Tier 1 Vaccines to Restore Public Confidence

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Overall, well done manuscript.  A few minor revisions suggested:

(1) Explain how the indiscriminate use of the term vaccine contributed to vaccine hesitancy (Page 2)  Vaccine hesitancy is more related to the information sources a person seeks.  It is not the term vaccine but rather misinformation regarding harmful effects of the vaccine (e.g. a chip is implanted in the COVID vaccine so the government could track people, etc.) - yes, it is absurd but people will believe it if they trust their information source or follow conspiracy theories.  

(2) Provide one example of for each of the Tiers to help better contextualize how the Tier is described.

(3) Explain context-dependent efficacy.  How is this term defined?

(4) I may have missed it, but it doesn't appear that Table 1 and Figure 1 are referred to in the narrative.  

(5) The narrative for The Spectrum of Vaccine Modalities (Figure 1) should be in the same order as seen in the Figure.  For example Viral Vector Vaccines is presented after mRNA vaccines but is seen in Figure 1 before mRNA vaccines.  

(6)The statement  "The misclassification of products with limited efficacy as vaccines has significantly eroded public trust" I think more than having high expectations of the effectiveness of the vaccine is important but the public trust is more related to politics and information sources.

 

Author Response

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Reviewer 2 Report

Comments and Suggestions for Authors

1) Citations are very very less.

2) Add more citations all across the paper.

3) You need to create a table and write name of Tier-1, Tier-2 and Tier-3 vaccines. If there is an overlap then you need to create a van diagram.

4) Section 2.1. is very informative. However, I suggest you to write the disease prevention aspect for each vaccine and their tier in table.

5) Reduce spacing in the table-1. 

6) Write the abbreviation of MMR, OPV, BCG, etc below the table-1.

7) Add one more column of exception and put exception vaccine of each class or tier there.

8) I found your work is very good. I have only 2 major recommendations: a) Add more citations. b) Add tables and figures for presenting different vaccines, sero efficacy, tier, etc. Also use some colors green, red, yellow/orange for showing each vaccine tier. 

9) The article is nicely written, but at the end of introduction, you need to add what are you going to discuss in the subsequent sections.

 

Author Response

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Reviewer 3 Report

Comments and Suggestions for Authors

dear authors, thank you for your work. it is well-done.

Author Response

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Reviewer 4 Report

Comments and Suggestions for Authors

The concept and work are exciting and novel; however, several sections overlap and are difficult to understand. Please arrange the sections.

Specific comments: 

1. Please rearrange the section for better understanding
2. In the introduction section, please highlight the relationship between today’s social media and the vaccination program. Currently, social media has become an integral part of human beings, and it has a direct or indirect effect on human life
3. In section 2, the author can also include the technological advancement of the vaccines
4. Tier 2 vaccines, please revise the description for better understanding
5. In the classification, several terms overlap. Please revise them
6. Include references in Table 1; importantly, please cite regulatory guidance
7. Figure 1, please include VLP and other forms of vaccines

 

Author Response

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Author Response File: Author Response.docx

Reviewer 5 Report

Comments and Suggestions for Authors

The manuscript presents a novel framework for stratifying vaccines that seeks to delineate platform categories in ways that can be grasped by non-experts. The authors’ purpose is laudable, and the timeliness of such clarifications is beyond dispute. Nevertheless, a careful examination suggests that the text is uneven in its objectivity, that it narrows the evidentiary base, and that it treats ethical uncertainties with an insufficiently dialogical stance. The evaluation persistently favors replication-competent live attenuated vaccines, particularly those with direct author ties, while portraying mRNA and viral-vector modalities in an unduly negative light. Claims about differential effects on mucosal immunity and horizontal viral spread are advanced with excessive certainty, neglecting crucial contingencies such as variability in formulation components, population representativeness, and the precise clinical endpoints in diverse trial designs. Certain citations are relevant, yet the overall reference list is conspicuously incomplete. Randomized studies, WHO consensus documents, and meta-analyses that adopt a tempered, integrative stance are notably missing. The argument thus reverts to a narrower selection of studies that merely corroborate the writers’ initial stance. To ensure both accuracy and comprehensiveness, the inclusion of a broader and more fairly represented spectrum of evidence is essential. Several self-references in the text appear strategically placed to endorse vaccine candidates linked to the authors’ institutions (e.g., Rational Vaccines’ RVx201). Nevertheless, the manuscript lacks an explicit declaration of any financial, institutional, or intellectual conflicts connected to these products. Because the text champions these platforms with notable vigor, an exhaustive and unequivocal disclosure is an essential ethical obligation. The manuscript consistently encloses terms like “vaccines” in quotation marks when discussing mRNA-derived products, a practice that undermines the document’s scientific gravitas and may be construed as implicit bias. Language throughout would benefit from a more measured, accurate, and technically correct register that aligns with professional norms. The proposal to reclassify several already licensed, regulator-approved vaccines as “immunomodulatory therapeutics” (Tier 3) entails far-reaching ethical, regulatory, and public health consequences. Comparative evidence and reference to existing policy frameworks do not adequately support this stance, and any premature implementation risks amplifying public confusion and eroding trust. The manuscript is, in general, logically organized; however, particular segments contain redundancy and excessive elaboration. For example, multiple paragraphs reiterate central points regarding mucosal immunity and the tier system. Streamlining these discussions and removing repetition would enhance clarity and strengthen overall persuasiveness.

Recommendation:
I recommend a thorough overhaul to resolve the concerns outlined above. By presenting the evidence more evenly, disclosing conflicts of interest more transparently, and engaging a wider spectrum of the literature, the manuscript stands a stronger chance of enriching the debate on vaccine policy and restoring public trust.

Author Response

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Round 2

Reviewer 4 Report

Comments and Suggestions for Authors

Thanks for the revision. I would like to recommend this work for publication 

Reviewer 5 Report

Comments and Suggestions for Authors

Accepted for publication