Evidence map›Paper›PMID 39794473›Full record

ArticleNature microbiology2025

A BCG kill switch strain protects against Mycobacterium tuberculosis in mice and non-human primates with improved safety and immunogenicity.

Alexander A Smith, Hongwei Su, Joshua Wallach, Yao Liu, Pauline Maiello, H Jacob Borish, Caylin Winchell, Andrew W Simonson, Philana Ling Lin, Mark Rodgers and 7 more

Abstract read
In one paragraph

Article in Nature microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Route of BCG administration determines success.Human vaccines & immunotherapeutics · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Alexander A Smith *Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Hongwei Su *Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.
Joshua Wallach *Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.
Yao LiuDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-4330-2389
Pauline MaielloDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-5188-8420
H Jacob BorishDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Caylin WinchellDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Andrew W SimonsonDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-4789-3873
Philana Ling LinThe Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Mark RodgersDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-9800-3362
Daniel FillmoreDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Jennifer SakalDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Kan LinDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.
Valerie VinetteDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.
Dirk SchnappingerDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA. dis2003@med.cornell.edu.ORCID http://orcid.org/0000-0002-4445-7219
Sabine EhrtDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA. sae2004@med.cornell.edu.ORCID http://orcid.org/0000-0002-7951-2310
JoAnne L FlynnDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. joanne@pitt.edu.ORCID http://orcid.org/0000-0001-7874-8981

Funding

IMMUNE MECHANISMS OF PROTECTION AGAINST MYCOBACTERIUM TUBERCULOSIS CENTER (IMPAC-TB)75N93019C00071 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI FORTUNE, SARAH · 2019 to 2025
$57.3M
Immunology of Infectious DiseaseT32AI060525 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JoAnne L. Flynn · 2005 to 2026
$5.3M
Development of a Self Inactivating, Highly Effective TB VaccineR01AI143788 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI EHRT, SABINE, FLYNN, JOANNE L. · 2019 to 2023
$3.9M
NCI NIH HHS HHSN261201000031CNCI NIH HHS HHSN261201500001CNCI NIH HHS HHSN261201500001GNCI NIH HHS HHSN261201500001WNCI NIH HHS HHSN261201500003CNCI NIH HHS HHSN261201500003INIAID NIH HHS 75N93019C00071NIAID NIH HHS R01 AI143788U.S. Department of Health & Human Services | National Institutes of Health (NIH) AI143788U.S. Department of Health & Human Services | National Institutes of Health (NIH) T32AI060525U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) HHSN2612015000031
6 · The paper itself

Abstract

Improved vaccination strategies for tuberculosis are needed. Intravenous (i.v.) delivery of live attenuated Mycobacterium bovis BCG provides protection against Mycobacterium tuberculosis (Mtb) in macaques but poses safety challenges. Here we genetically engineered two strains, BCG-TetON-DL and BCG-TetOFF-DL, to either induce or inhibit expression of two phage lysin operons, respectively, upon tetracycline exposure. We show that lysin expression kills BCG in vitro, in infected macrophages, and following infection of immunocompetent (C57BL/6) and immunocompromised (SCID) mice. Modified BCG elicited similar immune responses and provided similar protection against Mtb challenge as wild-type BCG in mice. In macaques, cessation of tetracycline treatment reduced i.v.-administered BCG-TetOFF-DL numbers. Intravenous BCG-TetOFF-DL increased pulmonary CD4 T-cell responses compared with wild-type BCG-induced responses and provided robust protection against Mtb challenge. Sterilizing immunity occurred in 6 of 8 macaques compared with 2 of 8 wild-type BCG-immunized macaques. Thus, a 'kill-switch' BCG strain provides additional safety and robust protection against Mtb infection.

Indexed as

BCG VaccineMycobacterium bovisMycobacterium tuberculosisTuberculosisAnimalsCD4-Positive T-LymphocytesFemaleMacacaMacrophagesMiceMice, Inbred C57BLMice, SCIDVaccines, AttenuatedBCG VaccineVaccines, Attenuated

Identifiers

PMID39794473
PMCPMC12756819

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.