The ‘experimental stable’ of the BCG vaccine: safety, efficacy, proof, and standards, 1921–1933

Bonah, Christian

doi:10.1016/j.shpsc.2005.09.003

Cited by 40 publications

(27 citation statements)

References 5 publications

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“…An infant was given three 2 mg doses (6 mg total; ~2.4 x 10 8 cfu) by the oral route. 27 There were no deleterious side effects and, most importantly, the child did not develop TB even though the infant's mother had died of TB shortly after giving birth. Over the next year, additional newborns were vaccinated and no ill effects were reported.…”

Section: Bcg: a Brief Historymentioning

confidence: 94%

“…For the first time, a safe and apparently effective vaccine was available for the prevention of human TB. 27 As early as 1924, cultures of BCG were distributed by the Institute Pasteur to laboratories around the world. 25 The implementation of BCG varied from country to country, and several fascinating histories have been written about specific strains (e.g., BCG-Japan 28 and BCG-Moreau 29 ).…”

Section: Bcg: a Brief Historymentioning

confidence: 99%

“…27 Research addressed questions of standardization, target populations (groups at risk), routes of administration and the utility of booster vaccinations. Issues related to the types of BCG strains phoP-phoR.…”

Section: Correlation With Residual Virulence and Reactogenicitymentioning

confidence: 99%

“…27 Over the following decades, numerous researches showed that BCG indeed never reverted to pathogenicity and the low virulence of existing strains was confirmed directly through the vaccinations of humans. However, marked differences in the residual virulence, immunogenic and sensitizing potency of BCG strains were also demonstrated in animal models of infection, 19,44 which raised the concern that certain BCG strains might not be virulent enough to be effective in humans.…”

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

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: Bcg: a Brief Historymentioning

confidence: 94%

Section: Bcg: a Brief Historymentioning

confidence: 99%

Section: Correlation With Residual Virulence and Reactogenicitymentioning

confidence: 99%

Section: Correlation With Immunogenicity and Protective Efficacymentioning

confidence: 99%

See 2 more Smart Citations

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

Liu

Tran²,

Leung³

et al. 2009

Human Vaccines

123

117

View full text Add to dashboard Cite

show abstract

“…MOJ Immunol 2016, 3 (2): 00085 elusive to the scientific community in terms of its interaction with the host and its ability to evade the immune system. Unlike other bacteria, Mycobacterium tuberculosis has eluded us in our understanding of its complex genes that gives the pathogen an added survival advantage.…”

Section: Mini Reviewmentioning

confidence: 99%