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Reviews of "A "suicide" BCG Strain provides Enhanced Immunogenicity and Robust Protection against Mycobacterium Tuberculosis in Macaques"

Reviewers: K Dobos & P Sanghvi (Colorado State University) | 📗📗📗📗◻️ • M Behr & H Salam (McGill University) | 📗📗📗📗◻️ • M Maeurer (University of Mainz) | 📘📘📘📘📘 • W Jacobs (Albert Einstein College of Medicine) | 📘📘📘📘📘

Published onJan 11, 2024
Reviews of "A "suicide" BCG Strain provides Enhanced Immunogenicity and Robust Protection against Mycobacterium Tuberculosis in Macaques"
key-enterThis Pub is a Review of
A “suicide” BCG strain provides enhanced immunogenicity and robust protection against Mycobacterium tuberculosis in macaques
A “suicide” BCG strain provides enhanced immunogenicity and robust protection against Mycobacterium tuberculosis in macaques
Description

Abstract Intravenous (IV) BCG delivery provides robust protection against Mycobacterium tuberculosis (Mtb) in macaques but poses safety challenges. Here, we constructed two BCG strains (BCG-TetON-DL and BCG-TetOFF-DL) in which tetracyclines regulate two phage lysin operons. Once the lysins are expressed, these strains are cleared in immunocompetent and immunocompromised mice, yet induced similar immune responses and provided similar protection against Mtb challenge as wild type BCG. Lysin induction resulted in release of intracellular BCG antigens and enhanced cytokine production by macrophages. In macaques, cessation of doxycycline administration resulted in rapid elimination of BCG-TetOFF-DL. However, IV BCG-TetOFF-DL induced increased pulmonary CD4 T cell responses compared to WT BCG and provided robust protection against Mtb challenge, with sterilizing immunity in 6 of 8 macaques, compared to 2 of 8 macaques immunized with WT BCG. Thus, a “suicide” BCG strain provides an additional measure of safety when delivered intravenously and robust protection against Mtb infection.

To read the original manuscript, click the link above.

Summary of Reviews: The reviewers found this preprint demonstrating a genetically engineered, tetracycline-regulated "suicide" BCG vaccine strain reliable to strong. It shows improved CD4 T cell responses and sterilizing immunity in macaques comparable to wild type BCG, though protection was not clearly superior to previous BCG studies. Reviewers suggested modifying the title to highlight safety and comparable protection, verifying statistical calculations, providing supplementary data, and conducting further experiments to support conclusions.

Reviewer 1 (Karen D… & Purva S…) | 📗📗📗📗◻️

Reviewer 2 (Marcel B… & Humza S…) | 📗📗📗📗◻️

Reviewer 3 (Markus M…) | 📘📘📘📘📘

Reviewer 4 (William J…) | 📘📘📘📘📘

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

To read the reviews, click the links below. 

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