A novel recombinant BCG vaccine using a mycobacteriophage promoter shows improved protection against tuberculosis
Abstract
The limited efficacy of conventional bacillus Calmette-Guerin (BCG) vaccination against adult pulmonary tuberculosis highlights the need for improved vaccine strategies. Genome integration can overcome the plasmid instability of recombinant BCG, but we hypothesized that this approach would be constrained by reduced transcriptional activity of conventional promoters when present as a single genomic copy. Here we identified P79, a mycobacteriophage-derived promoter that sustains high-level expression from a single genomic locus and used it to construct a genome-integrated recombinant BCG, termed LRC-BCG. LRC-BCG secretes the HSP70-MMPII fusion antigen flanked by the PEST sequences, maintained stable antigen expression over serial passages, and induced strong activation of macrophages and dendritic cells in vitro. In vivo, LRC-BCG inhibited Mycobacterium tuberculosis multiplication more effectively than conventional BCG, even at low doses. These findings demonstrate the feasibility of using P79 for stable genome-integrated recombinant BCG and support LRC-BCG as a promising tuberculosis vaccine candidate.
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BibTeX
@misc{tsukamoto2026novel,
title = {{A novel recombinant BCG vaccine using a mycobacteriophage promoter shows improved protection against tuberculosis}},
author = {Y. Tsukamoto and Y. Tsujimura and T. Mukai and T. Tamura and Y. Maeda and S. Torigoe and H. Saiga and M. N. Asaka and T. Komine and Y. Miyamoto and M. Nakaya and M. Makino and M. Ato},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.04.749280},
url = {https://www.biorxiv.org/content/10.64898/2026.09.04.749280v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A novel recombinant BCG vaccine using a mycobacteriophage promoter shows improved protection against tuberculosis
AU - Y. Tsukamoto
AU - Y. Tsujimura
AU - T. Mukai
AU - T. Tamura
AU - Y. Maeda
AU - S. Torigoe
AU - H. Saiga
AU - M. N. Asaka
AU - T. Komine
AU - Y. Miyamoto
AU - M. Nakaya
AU - M. Makino
AU - M. Ato
PY - 2026
DA - 2026/09/04
PB - bioRxiv
DO - 10.64898/2026.09.04.749280
UR - https://www.biorxiv.org/content/10.64898/2026.09.04.749280v1
AB - The limited efficacy of conventional bacillus Calmette-Guerin (BCG) vaccination against adult pulmonary tuberculosis highlights the need for improved vaccine strategies. Genome integration can overcome the plasmid instability of recombinant BCG, but we hypothesized that this approach would be constrained by reduced transcriptional activity of conventional promoters when present as a single genomic copy. Here we identified P79, a mycobacteriophage-derived promoter that sustains high-level expression from a single genomic locus and used it to construct a genome-integrated recombinant BCG, termed LRC-BCG. LRC-BCG secretes the HSP70-MMPII fusion antigen flanked by the PEST sequences, maintained stable antigen expression over serial passages, and induced strong activation of macrophages and dendritic cells in vitro. In vivo, LRC-BCG inhibited Mycobacterium tuberculosis multiplication more effectively than conventional BCG, even at low doses. These findings demonstrate the feasibility of using P79 for stable genome-integrated recombinant BCG and support LRC-BCG as a promising tuberculosis vaccine candidate.
ER -