{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T08:15:47Z","timestamp":1740125747991,"version":"3.37.3"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100004484","name":"Tehran University of Medical Sciences and Health Services","doi-asserted-by":"publisher","award":["40984"],"award-info":[{"award-number":["40984"]}],"id":[{"id":"10.13039\/501100004484","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003968","name":"Iran National Science Foundation","doi-asserted-by":"crossref","award":["98009344"],"award-info":[{"award-number":["98009344"]}],"id":[{"id":"10.13039\/501100003968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Investigate the genetic stability of the BCG vaccine produced in Iran from different batches compared to the reference strain.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We comparatively analyzed the whole genome sequences of the vaccine batches from different years. Eleven vials of different batches from 2010, 2018, and 2019 were included. Complete genome analyses revealed no difference between the old (2010) and new (2018 and 2019) vaccine batches. Additionally, minor genetic changes include five single nucleotide polymorphisms (SNPs) and insertions\/deletions (indels) were observed compared to the BCG Pasteur 1173P2 reference strain, which were shared among all batches. Besides, the batches were identical to the reference strain in terms of antibiotic resistance genes, prophage sequences, and clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>High genetic stability of the BCG vaccine used in the national immunization program was confirmed, which indicates the optimal conditions in the vaccine production process.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Significance and Impact of the Study<\/jats:title>\n                  <jats:p>Genetic differences within and between vaccine strains have been declared as one of the main parameters related to the BCG vaccine variable protective efficacy. No study has been done to investigate the genetic variations of the vaccine batches at the single-base level.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1111\/jam.15365","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T14:23:54Z","timestamp":1637159034000},"page":"2379-2388","source":"Crossref","is-referenced-by-count":3,"title":["Genomic evidence for stability of the Bacillus Calmette-Gu\u00e9rin (BCG) vaccine strain (Pasteur 1173P2) from different batches in Iran"],"prefix":"10.1093","volume":"132","author":[{"given":"Mahla","family":"Asadian","sequence":"first","affiliation":[{"name":"Division of Microbiology Department of Pathobiology School of Public Health Tehran University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azadeh","family":"Safarchi","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Biomolecular Sciences University of New South Wales Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyed Mehdi","family":"Hassanzadeh","sequence":"additional","affiliation":[{"name":"BCG Vaccine Production Plant Pasteur Institute of Iran Karaj Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehdi","family":"Yaseri","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics School of Public Health Tehran University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5861-3182","authenticated-orcid":false,"given":"Masoumeh","family":"Douraghi","sequence":"additional","affiliation":[{"name":"Division of Microbiology Department of Pathobiology School of Public Health Tehran University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,3,1]]},"reference":[{"key":"2023011711171950400_jam15365-bib-0001","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/978-3-319-64371-7_8","article-title":"Evolution and strain variation in BCG","volume":"1019","author":"Abdallah","year":"2017","journal-title":"Advances in Experimental Medicine and Biology"},{"volume-title":"FastQC: a quality control tool for high throughput sequence data","year":"2010","author":"Andrews","key":"2023011711171950400_jam15365-bib-0002"},{"key":"2023011711171950400_jam15365-bib-0003","doi-asserted-by":"crossref","first-page":"W16","DOI":"10.1093\/nar\/gkw387","article-title":"PHASTER: a better, faster version of the PHAST phage search tool","volume":"44","author":"Arndt","year":"2016","journal-title":"Nucleic Acids Research"},{"key":"2023011711171950400_jam15365-bib-0004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2164-9-75","article-title":"The RAST server: rapid annotations using subsystems technology","volume":"9","author":"Aziz","year":"2008","journal-title":"BMC Genomics"},{"key":"2023011711171950400_jam15365-bib-0005","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1089\/cmb.2012.0021","article-title":"SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing","volume":"19","author":"Bankevich","year":"2012","journal-title":"Journal of Computational Biology"},{"key":"2023011711171950400_jam15365-bib-0006","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1016\/S0264-410X(00)00369-8","article-title":"Identification of substrains of BCG vaccine using multiplex PCR","volume":"19","author":"Bedwell","year":"2001","journal-title":"Vaccine"},{"key":"2023011711171950400_jam15365-bib-0007","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/S1473-3099(02)00182-2","article-title":"BCG\u2014different strains, different vaccines?","volume":"2","author":"Behr","year":"2002","journal-title":"The Lancet Infectious Diseases"},{"key":"2023011711171950400_jam15365-bib-0008","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1126\/science.284.5419.1520","article-title":"Comparative genomics of BCG vaccines by whole-genome DNA microarray","volume":"284","author":"Behr","year":"1999","journal-title":"Science"},{"key":"2023011711171950400_jam15365-bib-0009","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1016\/j.vaccine.2015.02.056","article-title":"Variation of growth in the production of the BCG vaccine and the association with the immune response. 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