Development of New Tuberculosis Vaccines: A Global Perspective on Regulatory Issues

Brennan, Michael J.; Fruth, Uli; Milstien, Julie B.; Tiernan, Rosemary; Nishioka, Sérgio de Andrade; Chocarro, Liliana; Panel, TB Expert

doi:10.1371/journal.pmed.0040252

Cited by 39 publications

(20 citation statements)

References 17 publications

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“…BCG has a widely proven safety record and it is certainly one of the most frequently administered vaccines in the world [5]. In countries where TB is endemic, newborns are immunized with BCG immediately after birth since it protects infants from the most insidious forms of TB, such as disseminated infection and meningeal TB.…”

Section: Need For a New Vaccinementioning

confidence: 99%

Exploiting the mycobacterial cell wall to design improved vaccines against tuberculosis

Morandi

Sali

Manganelli

et al. 2013

J Infect Dev Ctries

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The only vaccine available against tuberculosis (TB), the Bacille Calmette-Guerin (BCG), does not provide effective protection against the most common forms of adult TB and in recent years efforts have been made to develop a new and improved vaccine. Among the strategies implemented, the generation of a new live attenuated mycobacterial strain is seen as one of the most promising and feasible, for scientific, ethical and practical reasons. The new understanding of the biology of the tubercle bacilli and of host-pathogen interaction processes, coupled with the possibility to engineer BCG or M. tuberculosis, opened new avenues to design "intelligent" vaccines, capable of eliciting the immune response associated with protection while avoiding the induction of the host immune response associated with immunopathology. The complex and highly immunogenic mycobacterial cell wall can shape the general and antigen specific immune response elicited following immunization, and the possibility to exploit this knowledge may lead to the development of new vaccines that could help conquer this ancient human disease.

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Section: Need For a New Vaccinementioning

confidence: 99%

Exploiting the mycobacterial cell wall to design improved vaccines against tuberculosis

Morandi

Sali

Manganelli

et al. 2013

J Infect Dev Ctries

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“…In fact, despite all the problems (2), BCG is still the gold standard vaccine in animal models and very few vaccines have provided better protection (13). Moreover, the introduction of an rBCG strain in human studies is seen as less problematic than the introduction of other live vaccines for ethical reasons (5,10). Overexpression of dominant antigens like the Ag85 complex (27,28) or reintroduction of selected genes lost during attenuation of BCG, like those from RD1, are two examples of the strategies implemented so far to develop rBCG (42).…”

mentioning

confidence: 99%

Surface Expression of MPT64 as a Fusion with the PE Domain of PE_PGRS33 EnhancesMycobacterium bovisBCG Protective Activity againstMycobacterium tuberculosisin Mice

Sali¹,

Sante²,

Cascioferro

et al. 2010

Infect Immun

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To improve the current vaccine against tuberculosis, a recombinant strain of Mycobacterium bovis bacillus Calmette-Guérin (rBCG) expressing a Mycobacterium tuberculosis vaccine candidate antigen (MPT64) in strong association with the mycobacterial cell wall was developed. To deliver the candidate antigen on the surface, we fused the mpt64 gene to the sequence encoding the PE domain of the PE_PGRS33 protein of M. tuberculosis (to create strain H PE-⌬MPT64-BCG), which we have previously shown to transport proteins to the bacterial surface. In a series of protection experiments in the mouse model of tuberculosis, we showed that (i) immunization of mice with H PE-⌬MPT64-BCG provides levels of protection significantly higher than those afforded by the parental BCG strain, as assessed by bacterial colonization in lungs and spleens and by lung involvement

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“…Revue gouvernance hiver 2011 2 (Kirigia et al 2005;Brennan et al 2007;Nyika et al 2009). À notre connaissance, il n'y a pas encore de consensus clair sur les facteurs qui influencent la régulation.…”

Section: Maïga Lamothe Williams-jones Et Blaisunclassified

Facteurs influençant la régulation des essais cliniques au Mali

Maïga¹,

Lamothe²,

Williams‐Jones³

et al. 2017

gouvernance

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Depuis 2005, le Mali participe à des activités de renforcement des autorités nationales de réglementation (ANR) initiées par l’OMS en vue d’une bonne régulation des essais cliniques. Malgré cette participation, il y a peu de régulation des essais et cette faiblesse s’explique en partie par un manque d’appropriation des mesures par les autorités nationales. Ainsi, il semble essentiel de comprendre quels facteurs influencent la régulation des essais cliniques, aspect encore peu étudié. En utilisant un cadre analytique basé sur la théorie néo-institutionnelle, cette étude qualitative à visée exploratoire, a été réalisée à partir d’entrevues semi-dirigées avec les ANR, les comités d’éthique, des chercheurs, des administrateurs, des praticiens hospitaliers et d’examens documentaires. Les résultats montrent que la configuration du champ organisationnel et la position des pouvoirs publics dans ce champ apparaissent essentiels à la compréhension des facteurs qui influencent la régulation des essais cliniques. La prépondérance des barrières à la régulation des essais, associée à l’incapacité des pouvoirs publics de renforcer la régulation et la faible structuration du champ organisationnel, plaident en faveur d’une réforme intégrale plutôt que pour l’adoption de mesures partielles comme, par exemple, les revues et inspections conjointes d’essais cliniques promues par l’OMS.

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Development of New Tuberculosis Vaccines: A Global Perspective on Regulatory Issues

Abstract: What are the regulatory challenges for testing and introducing investigative TB vaccines into countries where the disease is endemic?

Cited by 39 publications

References 17 publications

Exploiting the mycobacterial cell wall to design improved vaccines against tuberculosis

Exploiting the mycobacterial cell wall to design improved vaccines against tuberculosis

Surface Expression of MPT64 as a Fusion with the PE Domain of PE_PGRS33 EnhancesMycobacterium bovisBCG Protective Activity againstMycobacterium tuberculosisin Mice

Facteurs influençant la régulation des essais cliniques au Mali

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