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Reviews of "Therapeutic DNA Vaccine Targeting Mycobacterium Tuberculosis Persisters Shortens Curative Tuberculosis Treatment"

Reviewers: A Kupz (James Cook University) | ๐Ÿ“—๐Ÿ“—๐Ÿ“—๐Ÿ“—โ—ป๏ธ โ€ข A Cooper (University of Leicester) | ๐Ÿ“—๐Ÿ“—๐Ÿ“—๐Ÿ“—โ—ป๏ธ

Published onOct 24, 2024
Reviews of "Therapeutic DNA Vaccine Targeting Mycobacterium Tuberculosis Persisters Shortens Curative Tuberculosis Treatment"
key-enterThis Pub is a Review of
Therapeutic DNA Vaccine Targeting Mycobacterium tuberculosis Persisters Shortens Curative Tuberculosis Treatment
Therapeutic DNA Vaccine Targeting Mycobacterium tuberculosis Persisters Shortens Curative Tuberculosis Treatment
Description

Abstract Mycobacterium tuberculosis (Mtb) is one of the leading infectious causes of death worldwide. There is no available licensed therapeutic vaccine that shortens active tuberculosis (TB) disease drug treatment and prevents relapse, despite the World Health Organizationโ€™s calls. Here, we show that an intranasal DNA vaccine containing a fusion of the stringent response relMtb gene with the gene encoding the immature dendritic cell-targeting chemokine, MIP-3ฮฑ/CCL20, shortens the duration of curative TB treatment in immunocompetent mice. Compared to the first-line regimen for drug-susceptible TB alone, our novel adjunctive vaccine induced greater RelMtb-specific T-cell responses associated with optimal TB control in spleen, blood, lungs, mediastinal lymph nodes, and bronchoalveolar lavage (BAL) fluid. These responses were sustained, if not augmented, over time. It also triggered more effective dendritic cell recruitment, activation, and colocalization with T cells, implying enhanced crosstalk between innate and adaptive immunity. Moreover, it potentiated a 6-month TB drug-resistant regimen, rendering it effective across treatment regimens, and also showed promising results in CD4+ knockout mice, perhaps due to enhanced Rel-specific CD8+ T-cell responses. Notably, our novel fusion vaccine was also immunogenic in nonhuman primates, the gold standard animal model for TB vaccine studies, eliciting antigen-specific T-cell responses in blood and BAL fluid analogous to those observed in protected mice. Our findings have critical implications for therapeutic TB vaccine clinical development in immunocompetent and immunocompromised populations and may serve as a model for defining immunological correlates of therapeutic vaccine-induced protection.One sentence summary A TB vaccine shortens curative drug treatment in mice by eliciting strong TB-protective immune responses and induces similar responses in macaques.

To read the original manuscript, click the link above.

Summary of Reviews: The preprint shows promising results from murine experiments on the efficacy of a DNA vaccine (MIP-3ฮฑ/relMtb) in shortening tuberculosis treatment. One reviewer highlights its promise in drug-resistant TB and relapse prevention, praising the compelling evidence of shorter treatment duration in mice. The reviewer points out that the effectiveness of both non-human and human primates has not yet been established. Review #2 advocates for further clarity on immunological mechanisms and data presentation, while highlighting the vaccine's effectiveness in lowering bacterial burden and preventing relapse. In order to confirm wider applicability and improve experimental details, both reviewers suggest more research.

Reviewer 1 (Andreas Kโ€ฆ) | ๐Ÿ“—๐Ÿ“—๐Ÿ“—๐Ÿ“—โ—ป๏ธ

Reviewer 2 (Andrea Cโ€ฆ) | ๐Ÿ“—๐Ÿ“—๐Ÿ“—๐Ÿ“—โ—ป๏ธ

RR\ID Strength of Evidence Scale Key

๐Ÿ“• โ—ป๏ธโ—ป๏ธโ—ป๏ธโ—ป๏ธ = Misleading

๐Ÿ“™๐Ÿ“™ โ—ป๏ธโ—ป๏ธโ—ป๏ธ = Not Informative

๐Ÿ“’๐Ÿ“’๐Ÿ“’ โ—ป๏ธโ—ป๏ธ = Potentially Informative

๐Ÿ“—๐Ÿ“—๐Ÿ“—๐Ÿ“—โ—ป๏ธ = Reliable

๐Ÿ“˜๐Ÿ“˜๐Ÿ“˜๐Ÿ“˜๐Ÿ“˜ = Strong

To read the reviews, click the links below.ย 

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This preprint presents encouraging findings on a DNA vaccine (MIP-3ฮฑ/relMtb) for potentially shortening tuberculosis treatment. The murine study shows that the vaccine can reduce treatment duration and help prevent relapse, which could be especially valuable for drug-resistant TB. However, reviewers emphasize that its effectiveness in non-human and human primates remains unproven, and they recommend further research to clarify the vaccine's immunological mechanisms and improve data presentation. Additional studies are needed to confirm broader applicability and strengthen these preliminary results. Click here for more.