Evolution and Strain Variation in BCG

Abdallah, Abdallah; Behr, Marcel A.

doi:10.1007/978-3-319-64371-7_8

Cited by 45 publications

(44 citation statements)

References 81 publications

(107 reference statements)

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“…At that time, it constituted the main medical tool for the control of human TB. Only a few decades following the distribution of BCG stocks to vaccine production laboratories worldwide, different BCG producers recognized that there were variants of BCG; one explanation was the variability in passaging conditions in the different laboratories [5]. The lyophilization of stable BCG products was achieved in the 1950s and 1960s, but considerable evolution of the different BCG strains had already taken place.…”

Section: History and Evolution Of Tuberculosis Vaccinationmentioning

confidence: 99%

Development and Challenges in Animal Tuberculosis Vaccination

et al. 2020

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Vaccination with Bacillus Calmette–Guérin (BCG) constituted a major advance in the prevention of human tuberculosis (TB) in the beginning of the past century. BCG has also a clear potential for use in animals and, in particular, in the main domestic species subjected to TB control programs, cattle. Nowadays, the use of BCG vaccination against TB in cattle is not permitted by European Union legislation because BCG can induce a cellular immune response producing diagnostic interference in the eradication programs based on tuberculin single and comparative intradermal tests imposed worldwide. In this review, we recall the history of TB vaccination as well as different vaccine trials and the response to vaccination in both domestic and wild animals. Promising potential inactivated vaccines are also reviewed. Research studies are mainly focused to improve vaccine efficacy, and at the same time to ensure its easy administration, safety and stability in the environment. Great challenges remain, particularly in terms of vaccine candidates and also in the acceptance of vaccination. Vaccination should be included in a strategic plan for integrated control of TB under a “one health” perspective, which also includes other measures such as improved biosafety on farms to avoid or decrease contact between domestic and wild animals or control of wildlife reservoirs to avoid overabundance that may favor infection maintenance.

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Section: History and Evolution Of Tuberculosis Vaccinationmentioning

confidence: 99%

Development and Challenges in Animal Tuberculosis Vaccination

et al. 2020

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“…The most studied tuberculosis vaccine in deer, as well as other wildlife is the attenuated strain of M. bovis known as bacillus Calmette-Guérin (BCG), named for Albert Calmette and Camille Guérin, two French scientists at the Pasteur Institute that developed the strain ( 26 ). BCG vaccines are the oldest vaccines still in use today; moreover, with over four billion people vaccinated in over 180 countries it is history's safest and most widely used vaccine ( 27 ) and it remains the only approved tuberculosis vaccine for humans.…”

Section: History Of Bcgmentioning

confidence: 99%

“…In spite of what must have been significant exposure to virulent M. tuberculosis , the child developed normally with no signs of tuberculosis ( 33 ). In the following 3 months after this first vaccination, 317 infants were vaccinated and by 1924 more than 660 infants had been orally vaccinated ( 26 ). Oral, subcutaneous, intraperitoneal and intravenous routes of administration all proved safe.…”

Section: History Of Bcgmentioning

confidence: 99%

“…The original BCG was not cloned, but was distributed to many laboratories worldwide, where the vaccine was propagated, such that today there are many genetically variant BCG strains, none of which are identical to each other or to the original vaccine ( 26 , 32 , 38 ). The various substrains differ in immunogenicity and potency; a possible reason for historically large ranges of observed efficacy in human studies around the world ( 26 , 32 , 39 ). Currently, five strains account for >90% of the BCG used worldwide; Pasteur 1173 P2, Danish 1331, Glaxo 1077, Tokyo 172-1, Russian BCG-I and Moreau RDJ ( 40 ).…”

Section: History Of Bcgmentioning

confidence: 99%

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Use of the Human Vaccine, Mycobacterium bovis Bacillus Calmette Guérin in Deer

Palmer

Thacker

2018

Front. Vet. Sci.

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The only vaccine ever approved for human tuberculosis was developed a century ago from an isolate of Mycobacterium bovis derived from a tuberculous cow. Initial safety and efficacy studies of an attenuated version of this isolate were conducted in cattle and other animals. In 1921 the first human, an infant, was orally dosed with this attenuated strain that came to be known as M. bovis bacillus Calmette-Guérin (BCG); named for Albert Calmette and Camille Guérin, the two French scientists that developed the strain. Since 1921, billions of people have been vaccinated with BCG making it the oldest, most widely used, and safest vaccine in use today. It is also the tuberculosis vaccine most studied for use in wildlife, including deer. While BCG vaccination of deer may not reliably prevent infection, it consistently decreases lesion severity, minimizing large, necrotic lesions, which often contain large numbers of bacilli. It is believed that decreased lesion severity correlates with decreased disease transmission; however, this hypothesis remains to be proven. Safety studies in white-tailed deer show BCG may persist in lymphoid tissues for up to 12 months; a factor to be considered in deer used for food. Beyond efficacy and safety, methods of vaccine delivery to free-ranging deer are also under investigation, both in the laboratory and in the field. The ideal delivery method is effective, efficient and safe for non-target species, including livestock. Ingestion of BCG by cattle is of special concern as such cattle may present as “false positives” using currently approved diagnostic methods, thus interfering with efforts by animal health agencies to monitor cattle for tuberculosis. An effective BCG vaccine for deer would be of value in regions where free-ranging deer represent a potential source of M. bovis for livestock. Such a vaccine would also be beneficial to farmed deer where M. bovis represents a serious threat to trade and productivity.

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“…Therefore, the scheme contains two ‘BCG China’ strains: BCG China 8 and BCG China* 7, 13 . Adapted from refs 8, 11, 13, 16, 17 Concerning ref 8 , only the RD and deleted genes that could be verified on the assembled genomes are included.…”

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Reference genome for the WHO reference strain for Mycobacterium bovis BCG Danish, the present tuberculosis vaccine

Borgers

Zheng

et al. 2019

Preprint

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12Mycobacterium bovis bacillus Calmette-Guérin (M. bovis BCG) is the only vaccine available against 13 tuberculosis (TB). This study reports on an integrated genome analysis workflow for BCG, resulting in the 14 completely assembled genome sequence of BCG Danish 1331 (07/270), one of the WHO reference strains 15 for BCG vaccines. We demonstrate how this analysis workflow enables the resolution of genome 16 duplications and of the genome of engineered derivatives of this vaccine strain. 17 MAIN TEXT 18The BCG live attenuated TB vaccine is one of the oldest and most widely used vaccines in human medicine. 19Each year, BCG vaccines are administered to over 100 million newborns (i.e. 75% of all newborns on the 20 planet). The original BCG strain was developed in 1921 at the Pasteur Institute, through attenuation of the 21 bovine TB pathogen M. bovis, by 231 serial passages on potato slices soaked in glycerol-ox bile over a time-22 span of 13 years 1 . This BCG Pasteur strain was subsequently distributed to laboratories around the world 23 and different laboratories maintained their own daughter strains by passaging. Over the years, different 24 substrains arose with different protective efficacy 2,3 . The establishment of a frozen seed-lot system in 1956 25 and the WHO recommendation of 1966 that vaccines should not be prepared from cultures that had 26 undergone >12 passages starting from a defined freeze-dried seed lot, halted the accumulation of 27 additional genetic changes 1 . In an effort to further standardize the vaccine production and to prevent 28 severe adverse reactions related to BCG vaccination, three substrains, i.e. Danish 1331, Tokyo 172-1 and 29Russian BCG-1 were established as the WHO reference strains in 2009 and 2010 4 . Of these, the BCG Danish 30 1331 strain is the most frequently used one, and it also serves as a basis of most current "next-generation" 31 engineering efforts to improve the BCG vaccine or to use it as a "carrier" for antigens of other pathogens 5,6 . 32Complete genome elucidation of BCG strains is challenging by the occurrence of large genome segment 33 2 duplications and a high GC content. Therefore, no fully assembled reference genome is yet available for 34 BCG Danish, only incomplete ones 7,8 , which hinders further standardization efforts. 35By combining second (Illumina) and third (PacBio) generation sequencing technologies and an integrated 36 bioinformatics workflow we have for the first time fully assembled the BCG Danish 1331 (07/270) strain 37 genome sequence. Ambiguous regions were locally reassembled and/or experimentally verified. The single 38 circular chromosome is 4,411,814 bp in length and encodes 4,084 genes, including 4,004 genes encoding 39 for proteins, 5 genes for rRNA, 45 genes for tRNA and 30 pseudogenes (Fig. 1a). Compared to the reference 40 genome sequence of BCG Pasteur 1173P2, 42 SNPs were identified and a selected subset was validated 41 Table 1 and 5). Genetic features determinative for BCG Danish, as described by Abdallah et al. 8 , 42 were ...

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Evolution and Strain Variation in BCG

Cited by 45 publications

References 81 publications

Development and Challenges in Animal Tuberculosis Vaccination

Development and Challenges in Animal Tuberculosis Vaccination

Use of the Human Vaccine, Mycobacterium bovis Bacillus Calmette Guérin in Deer

Reference genome for the WHO reference strain for Mycobacterium bovis BCG Danish, the present tuberculosis vaccine

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