Differential productions of lipid virulence factors among BCG vaccine strains and implications on BCG safety

Chen, Jeffrey M.; Islam, Salim T.; Ren, Hui; Liu, Jun

doi:10.1016/j.vaccine.2007.09.041

Cited by 62 publications

(74 citation statements)

References 41 publications

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“…However, in the past decade, the advances in genomic techniques and knowledge of the virulence mechanisms of M. tb have offered unprecedented opportunities to re-evaluate these traditional assumptions. Indeed, our recent studies have provided direct evidence that the distribution of major mycobacterial virulence factors varies among BCG lineages, 20,21 and suggests that different BCG substrains have different mechanisms of attenuation. This review article discusses these new developments and their impacts on vaccine properties, including safety, immunogenicity and protective efficacy.…”

Section: Attenuation Of Bcg Between 1908-1921mentioning

confidence: 99%

“…The direct evidence that BCG strains differ in established virulence factors first came from the comparative biochemical analysis of phthiocerol dimycocerosates (PDIMs) and phenolic glycolipids (PGLs). 21 52 The biosynthesis of PDIMs and PGLs has been a subject of intensive studies in recent years, 52 pioneered by Kolattukudy and co-workers. 53,54 The role of PDIMs and PGLs in virulence has now been well established.…”

Section: Bcg: a Brief Historymentioning

confidence: 99%

“…57 Analysis of 12 BCG strains reveals that BCG-Japan, BCG-Moreau and BCG-Glaxo do not produce PDIMs and PGLs, whereas the other BCG strains do (Table 1). 21 Intriguingly, variation in PDIM and PGL production does not coincide with the genealogy of BCG strains, 43 suggesting that this particular phenotype has emerged multiple times and by multiple mechanisms. Indeed, in BCG-Moreau, the PDIM and PGL defect is likely due to a 975 bp deletion that affects fadD26 and ppsA, 20 which are part of the biosynthetic locus of PDIMs and PGLs.…”

Section: Bcg: a Brief Historymentioning

confidence: 99%

“…As discussed in the previous section, BCG-Japan, -Moreau and -Glaxo do not produce PDIMs and PGLs. 21 BCG-Prague is a natural phoP mutant. 20 Given the well-established roles of PDIM/PGL and phoP in the virulence of M. tb and M. bovis, there is little doubt that these four BCG strains are more attenuated than other BCG strains, which is in a perfect agreement with the evidence from animal infections and clinical studies.…”

Section: © 2 0 0 9 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 99%

“…14 The tuberculin reactivity does not appear to be simply correlated with the virulence level of BCG strains. For instance, BCG-Japan, considered to be the most attenuated, 21 is also one of the strongest inducers of tuberculin reactivity in children. 99 Thus, the exceptionally low tuberculin conversion of BCG-Prague is likely explained specifically by the phoP mutation.…”

Section: Correlation With Immunogenicity and Protective Efficacymentioning

confidence: 99%

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BCG Vaccines: Their mechanisms of attenuation and impact on safety and protective efficacy

Liu

Tran²,

Leung³

et al. 2009

Human Vaccines

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123

117

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by MDR strains that are also resistant to a fluoroquinolone and at least one second-line injectable agent (amikacin, kanamycin and/or capreomycin), caught the world's attention after an outbreak in KwaZulu-Natal, South Africa, where 52 of 53 infected patients died. 2 HIV co-infection was a contributing factor in most of these deaths, and indeed, a deadly association between HIV and TB has been known almost since the start of the HIV-epidemic. Of the 1.7 million people who died from TB in 2006, an estimated 200,000 were co-infected with HIV. 1 Because of these situations, effective approaches alternative to antibiotics are urgently needed for the control of TB.Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis (M. bovis), is currently the only available vaccine against TB. Since 1974, BCG vaccination has been included in the WHO Expanded Program on Immunization. 3 It is estimated that more than 3 billion individuals have been immunized with BCG and over 100 million doses of BCG are administered annually, making it the most widely used vaccine in humans. 3 Meta-analysis studies have confirmed that BCG protects children, providing >80% efficacy against severe forms of TB, including tuberculous meningitis and miliary TB. 4,5 In contrast, evidence for protection against pulmonary TB in adolescents and adults remains contentious as efficacy estimates from clinical trials, observational case control studies and contact studies range from 0 to 80%. 6,7 The reasons for the variable protective efficacy are unknown but several hypotheses have been proposed, including differences among the vaccine strains used in clinical studies, exposure of trial populations to environmental mycobacteria, nutritional or genetic differences in human populations, differences in trial methods, and variations among clinical M. tb strains. 8-13 These explanations are not mutually exclusive and all may contribute to the heterogeneity in vaccine efficacy.A key aspect of this issue may concern the nature of BCG attenuation. Although it is generally considered safe and has been used as a human vaccine since the 1920s, the mechanisms of BCG attenuation remain largely unknown. This is further complicated by the fact that BCG is not a single strain, but instead comprises a number of substrains that exhibit phenotypic and biochemical differences. 14 BCG strains also exhibit differences in residual virulence level. [15][16][17] However, side effects were often attributed to variations in the viability of vaccines during preparation procedures (e.g., freezedrying). 14 In other words, the observed differential virulence among Mycobacterium bovis Bacille Calmette-Guérin (BCG) was developed as an attenuated live vaccine for tuberculosis control nearly a century ago. Despite being the most widely used vaccine in human history, the mechanisms of attenuation of BCG remain poorly understood. BCG is not a single organism, but comprises a number of substrains that differ in genotypes and phenotypes. The impacts of these differences on BCG...

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Section: Attenuation Of Bcg Between 1908-1921mentioning

confidence: 99%

Section: Bcg: a Brief Historymentioning

confidence: 99%

Section: Bcg: a Brief Historymentioning

confidence: 99%

Section: © 2 0 0 9 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 99%

Section: Correlation With Immunogenicity and Protective Efficacymentioning

confidence: 99%

See 3 more Smart Citations

BCG Vaccines: Their mechanisms of attenuation and impact on safety and protective efficacy

Liu

Tran²,

Leung³

et al. 2009

Human Vaccines

Self Cite

123

117

View full text Add to dashboard Cite

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Total Synthesis of the Phenolic Glycolipid Mycoside B and the Glycosylated p‐Hydroxybenzoic Acid Methyl Ester HBAD‐I, Virulence Markers of Mycobacterium tuberculosis

Barroso¹,

Geerdink²,

Horst³

et al. 2013

Eur J Org Chem

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The phenolic glycolipid mycoside B, present in Mycobacterium bovis and hypervirulent strains of Mycobacterium tuberculosis, has been synthesized for the first time. Multiple methyl groups were introduced by the extensive use of catalytic asymmetric 1,4‐addition reactions, asymmetric hydrogenation of a β‐keto ester afforded the basis for the central 1,3‐diol moiety, and introduction of the 2‐O‐methyl‐α‐L‐rhamnoside unit was achieved by stereoselective glycosylation with p‐iodophenol and subsequent Sonogashira coupling, providing a basis for the generation of analogues. In addition, the related monosaccharide HBAD‐I, present in the same species, has been efficiently synthesized for the first time by selective methylation of the hydroxy group at C‐2 of a rhamnoside.

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Evolution and Strain Variation in BCG

Abdallah

Behr

2017

Advances in Experimental Medicine and Biology

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BCG vaccines were derived by in vitro passage, during the years 1908-1921, at the Pasteur Institute of Lille. Following the distribution of stocks of BCG to vaccine production laboratories around the world, it was only a few decades before different BCG producers recognized that there were variants of BCG, likely due to different passaging conditions in the different laboratories. This ultimately led to the lyophilization of stable BCG products in the 1950s and 1960s, but not before considerable evolution of the different BCG strains had taken place. The application of contemporary research methodologies has now revealed genomic, transcriptomic and proteomic differences between BCG strains. These molecular differences in part account for phenotypic differences in vitro between BCG strains, such as their variable secretion of antigenic proteins. Yet, the relevance of BCG variability for immunization policy remains elusive. In this chapter we present an overview of what is known about BCG evolution and its resulting strain variability, and provide some speculation as to the potential relevance for a vaccine given to over 100 million newborns each year.

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Differential productions of lipid virulence factors among BCG vaccine strains and implications on BCG safety

Cited by 62 publications

References 41 publications

BCG Vaccines: Their mechanisms of attenuation and impact on safety and protective efficacy

BCG Vaccines: Their mechanisms of attenuation and impact on safety and protective efficacy

Total Synthesis of the Phenolic Glycolipid Mycoside B and the Glycosylated p‐Hydroxybenzoic Acid Methyl Ester HBAD‐I, Virulence Markers of Mycobacterium tuberculosis

Evolution and Strain Variation in BCG

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