Evidence map›Paper›PMID 36765273›Full record

ArticleBMC genomics2023

Genome sequences of BCG Pasteur ATCC 35734 and its derivative, the vaccine candidate BCGΔBCG1419c.

Giuseppe D'Auria, Yordan Hodzhev, Michel de Jesús Aceves-Sánchez, Andrés Moya, Stefan Panaiotov, Mario Alberto Flores-Valdez

Abstract read
In one paragraph

Article in BMC genomics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

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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

2 citing papers in PubMed.

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4 · The record

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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

6 authors.

Giuseppe D'Auria *Sequencing and Bioinformatics Service, Foundation for the Promotion of Health and Biomedical Research of Valencia Region, FISABIO, Valencia, Spain.
Yordan Hodzhev *National Center of Infectious and Parasitic Diseases, 1504, Sofia, Bulgaria.
Michel de Jesús Aceves-SánchezBiotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y diseño del Estado de Jalisco, A.C., Av. Normalistas 800, Col. Colinas de la Normal, 44270, Guadalajara, Jalisco, Mexico.
Andrés MoyaArea of Genomics and Health, Foundation for the Promotion of Sanitary and Biomedical Research of Valencia Region (FISABIO-Public Health), Valencia, Spain.
Stefan PanaiotovNational Center of Infectious and Parasitic Diseases, 1504, Sofia, Bulgaria. spanaiotov@ncipd.org.
Mario Alberto Flores-ValdezBiotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y diseño del Estado de Jalisco, A.C., Av. Normalistas 800, Col. Colinas de la Normal, 44270, Guadalajara, Jalisco, Mexico. floresv@ciatej.mx.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBacillus Calmette-Guérin (BCG) remains the only vaccine to prevent tuberculosis (TB) during childhood, with relatively low to no efficacy against pulmonary TB in adolescents and adults. BCG consists of close to 15 different substrains, where genetic variations among them might contribute to the variable protective efficacy afforded against pulmonary TB. We have shown that the vaccine candidate, BCGΔBCG1419c, which is based on BCG Pasteur, improved protection against chronic TB in murine models, as well as against pulmonary and extrapulmonary TB in guinea pigs. Here, to confirm deletion of the BCG1419c gene and to detect possible genetic variations occurring as a consequence of the spontaneous mutations that may arise during in vitro culture of mycobacteria, the genomes of BCG Pasteur ATCC 35734 and its isogenic derivative, BCGΔBCG1419c, were sequenced and subjected to a comparative analysis between them and against BCG Pasteur 1173P2.

resultsThe complete catalog of variants in genes relative to the reference genome BCG Pasteur 1173P2 (GenBank NC008769) showed that the parental strain BCG Pasteur ATCC 35734, from which the mutant BCGΔBCG1419c originated, showed five synonymous mutations, three missense mutations, and five codon insertions, whereas the BCGΔBCG1419c mutant reported the same changes. When BCG Pasteur ATCC 35734 and BCGΔBCG1419c were compared, we confirmed that the latter was devoid of the BCG1419c gene, with only one unanticipated SNP at position 2, 828, 791  which we consider has no role in vaccine properties reported thus far.

conclusionWe provide evidence that the mutagenesis performed to remove BCG1419c from BCG Pasteur ATCC 35734 solely deleted this gene, and that compared with the reference strain BCG Pasteur 1173P2, few changes were present confirming that they are BCG Pasteur strains, and that changes in immunogenicity or efficacy observed thus far in BCGΔBCG1419c are most likely derived solely from the elimination of the BCG1419c gene.

Indexed as

Mycobacterium bovisTuberculosisTuberculosis, PulmonaryAnimalsBCG VaccineGenomeGuinea PigsMiceBCG VaccineBCGBCGΔBCG1419cGenomic analysisPasteurVaccine

Identifiers

PMID36765273
PMCPMC9912546

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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.