Structured PREreview of Mycobacterial EsxG·EsxH (TB9.8·TB10.4) peptides as a subunit vaccine to booster BCG vaccination in an experimental model of pulmonary Tuberculosis

Does the introduction explain the objective of the research presented in the preprint?

Yes

Yes, it addresses a critical issue in TB vaccine development because it proposes a peptide-based booster for the BCG vaccine. The BCG vaccine has stood for over 100 years, and some people do not respond to it well because new strains of Mtb have emerged over time, making some of the strains evade the effect of BCG.

Are the methods well-suited for this research?

Somewhat appropriate

A robust methodology was used in the study, which included peptide synthesis, cytotoxicity testing, immunogenicity test, and even the Mtb chances that occur in mice. Bioinformatic tools are used to find the peptides that have high binding affinity to MHC-II molecules, which has the potentiality of eliciting a robust immune response. These peptides have been observed in many Mtb strains, and this has the advantage of reducing the ability of the immune system to escape. The study appropriately assesses the safety of the peptides using alveolar macrophages, though the high toxicity of G2 would raise concerns about its suitability as a vaccine candidate. Evaluation of cytokine production, especially TNF-α, interferes with IFN-γ, IL-2, and memory T cells responses is comprehensively done. However, the study gives inconsistent cytokine production, which may undermine its claims about the efficacy of the vaccine. The study has also used two strains of Mtb (H37 Rv and 09005186), allowing for comparison between a reference (H37 Rv) and a hypervirulent clinical isolate (09005186). The analysis employs ANOVA and Log RANK test, which is appropriate for this study, but more details on effect size and confident intervals would improve transparency. This would help determine the magnitude and reliability of the observed effect, hence the validity of the study conclusions. Furthermore, the study lacks longitudinal immunity data. It only emphasizes immune responses at different time points but fails to investigate the long-term protection of the vaccine. Although different peptide doses are tested, the study fails to give a clearer correlation between dose and the protective efficacy that is needed. Again, the study does not elucidate how the findings could be applied to human clinical trials, making it a bit difficult to assess the implications of the findings. Lastly, the study mentions potential genetic variations in Mtb strains affecting the efficacy of the vaccine but fails to investigate the effects experimentally.

Are the conclusions supported by the data?

Highly supported

The conclusions are supported by the data because the study contributes to valuable insights into TB vaccine development, particularly the use of peptide boosters. However, further experimental validations would be necessary to confirm the immunogenic potential of the peptide-based booster in vivo.

Are the data presentations, including visualizations, well-suited to represent the data?

Highly appropriate and clear

Data presentation is aided by relevant graphs and tables

How clearly do the authors discuss, explain, and interpret their findings and potential next steps for the research?

Very clearly

They provide a comprehensive insight into cellular response induced by the four peptides. The findings are also consistent with the reported literature. The researchers propose the exploration of mechanisms behind the responses elicited by the peptides that were used.

Is the preprint likely to advance academic knowledge?

Highly likely

The study elucidates immune responses elicited by the four peptides, i.e, G1, G2, H1, and H2, yet identifies a gap for further research on the exploration of the mechanism behind such responses.

Would it benefit from language editing?

No

There may be minor errors that might benefit from language editing.

Would you recommend this preprint to others?

Yes, it’s of high quality

Is it ready for attention from an editor, publisher or broader audience?

Yes, after minor changes

Competing interests

The authors declare that they have no competing interests.