Extended safety studies of the attenuated live tuberculosis vaccine SO2 based on phoP mutant

Cardona, Père-Joan; Gonzalo-Asensio, Jesús; Arbués, Ainhoa; Otal, Isabel; Lafoz, Carmen; Gil, Olga; Cáceres, Neus; Ausina, V.; Gicquel, Brigitte; Martín, Carlos

doi:10.1016/j.vaccine.2009.02.060

Cited by 50 publications

(29 citation statements)

References 35 publications

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“…H37RvΔphoP shows reduced growth in vitro, is impaired in replication in BMMΦ and in mice [74] Involved in the biosynthesis of lipids [75] Functionally linked with ESX-1 system [73] SO2 mutant is more attenuated than BCG, eliciting high protection in mice and superior protection in guinea pigs [17] SO2 mutant is safe once used as liveattenuated vaccine against TB [77] SigE As ECF, is involved in response to surface stress such as heat-shock, SDS [85] Its depletion in H37Rv results in attenuation in HMΦ and MMΦ, and is more sensitive to killing in the latter [85] SigE null mutant is unable to grow in THP1-MΦ and severely attenuated in mice [85,86] SigE mutant elicits stronger immune response (IFN-γ and TNF-α) and improved protection than BCG in mouse model of TB once administered as liverecombinant vaccine [87] PE delivery system PE domain of PE_PGRS33 delivers proteins to the mycobacterial surface [95,96] Fusion of antigens with the PE domain results in the expression of the latter on the surface [96] which can result in higher immunogenicity and protective activity when employed for rBCG engineering [99] Exploiting the mycobacterial surface M. tuberculosis is an elusive pathogen and as such is an active manipulator of the host immune system, exploiting a large arsenal of biomolecules which allows the bacilli to interact with a wide array of immune ligands [26,27]. Most of these biomolecules are localized in the complex mycobacterial cell wall, which has a very peculiar composition known to play a pivotal role in the pathogenesis of mycobacterial infections.…”

Section: Phopmentioning

confidence: 99%

“…PhoP controls the synthesis of complex mycobacterial lipids which exhibit immunomodulatory properties; in addition to abrogating the secretion of Esat-6, inactivation of phoP in the M. tuberculosis SO2 strain results in significant changes in the mycobacterial cell wall composition [75,76]. As of today, the M. tuberculosis SO2 attenuated strain is one of the new TB vaccines in the most advanced stage of development and the results obtained so far are promising [77].…”

Section: Esx-1mentioning

confidence: 99%

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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: Phopmentioning

confidence: 99%

Section: Esx-1mentioning

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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show abstract

“…Good results with this mutant have been reported in in vitro studies, as well as in mice, guinea pigs, and macaques (45)(46)(47)(48), and an attraction of this candidate is that, unlike BCG, it appears to be a good inducer of central memory T cell responses.…”

Section: Conventional Vaccines Establishing Acquired Specific Resistancementioning

confidence: 88%

Tuberculosis Vaccine Types and Timings

Orme¹

2014

Clin. Vaccine Immunol.

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Traditionally, the design of new vaccines directed against Mycobacterium tuberculosis, the most successful bacterial pathogen on the planet, has focused on prophylactic candidates that would be given to individuals while they are still young. It is becoming more apparent, however, that there are several types of vaccine candidates now under development that could be used under various conditions. Thus, in addition to prophylactic vaccines, such as recombinant Mycobacterium bovis BCG or BCG-boosting vaccines, other applications include vaccines that could prevent infection, vaccines that could be given in emergency situations as postexposure vaccines, vaccines that could be used to facilitate chemotherapy, and vaccines that could be used to reduce or prevent relapse and reactivation disease. These approaches are discussed here, including the type of immunity we are trying to specifically target, as well as the limitations of these approaches.

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“…Importantly, the SO2 strain is fully susceptible to four frontline antimycobacterial drugs (ethambutol, isoniazid, rifampin, and streptomycin) in vivo and does not induce adverse effects following vaccination in guinea pigs previously exposed to M. tuberculosis (20). The SO2 strain is also protective in rhesus monkeys, suggesting real promise that a phoP mutant could be further evaluated for use as an effective live vaccine in humans (163).…”

Section: Vol 75 2011 Tcss In Mycobacterium 571mentioning

confidence: 99%

Adaptation to Environmental Stimuli within the Host: Two-Component Signal Transduction Systems of Mycobacterium tuberculosis

Bretl

Demetriadou

Zahrt

2011

Microbiol Mol Biol Rev

128

133

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SUMMARY Pathogenic microorganisms encounter a variety of environmental stresses following infection of their respective hosts. Mycobacterium tuberculosis , the etiological agent of tuberculosis, is an unusual bacterial pathogen in that it is able to establish lifelong infections in individuals within granulomatous lesions that are formed following a productive immune response. Adaptation to this highly dynamic environment is thought to be mediated primarily through transcriptional reprogramming initiated in response to recognition of stimuli, including low-oxygen tension, nutrient depletion, reactive oxygen and nitrogen species, altered pH, toxic lipid moieties, cell wall/cell membrane-perturbing agents, and other environmental cues. To survive continued exposure to these potentially adverse factors, M. tuberculosis encodes a variety of regulatory factors, including 11 complete two-component signal transduction systems (TCSSs) and several orphaned response regulators (RRs) and sensor kinases (SKs). This report reviews our current knowledge of the TCSSs present in M. tuberculosis . In particular, we discuss the biochemical and functional characteristics of individual RRs and SKs, the environmental stimuli regulating their activation, the regulons controlled by the various TCSSs, and the known or postulated role(s) of individual TCSSs in the context of M. tuberculosis physiology and/or pathogenesis.

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Extended safety studies of the attenuated live tuberculosis vaccine SO2 based on phoP mutant

Cited by 50 publications

References 35 publications

Exploiting the mycobacterial cell wall to design improved vaccines against tuberculosis

Exploiting the mycobacterial cell wall to design improved vaccines against tuberculosis

Tuberculosis Vaccine Types and Timings

Adaptation to Environmental Stimuli within the Host: Two-Component Signal Transduction Systems of Mycobacterium tuberculosis

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