MTBVAC vaccine is safe, immunogenic and confers protective efficacy against Mycobacterium tuberculosis in newborn mice

Aguilo, Nacho; Uranga, Santiago; Marinova, Dessislava; Monzón, Marta; Badiola, Juan José; Martín, Carlos

doi:10.1016/j.tube.2015.10.010

Cited by 49 publications

(39 citation statements)

References 17 publications

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“…Additionally, biodistribution and formal toxicity studies showed that intradermal inoculation of MTBVAC presents lack of toxicity, limited organ biodistribution and persistence, and untraceable excretion in urine and stool up to six months post vaccination, comparable to BCG SSI, as well as appears to be less reactogenic than BCG in mice and guinea pigs [39]. Finally, in newborn mice MTBVAC and BCG SSI presented a comparable safety and lack of toxicity profile, as measured by health appearance, normal growth and development behavior, survived until fixed end point (6 months), and there were no effects on organ development at necropsy [71].…”

Section: Preclinical Characterization Of Mtbvacmentioning

confidence: 80%

“…Moreover, upon M. tuberculosis challenge, SO2 group showed significantly greater recall of vaccine-induced memory cells to secondary infection which was of increased magnitude compared to that of the BCG group [67]. In newborn C57BL/6 mice, MTBVAC vaccination induced differential immune response to Ag85B compared to BCG vaccination, as measured by IFNγ secretion in splenocytes [71]. A plausible explanation for these differential immune responses to Ag85B between MTBVAC (or SO2) and BCG could be due to an acquired point mutation in the fbpB gene in all BCG sub-strains, which results in an unstable protein [50].…”

Section: Protective Efficacy and Immunogenicity Of Mtbvac And Prototymentioning

confidence: 90%

“…Serum C-reactive protein assessment indicated that vaccination with prototype SO2 or BCG Danish leads to significant reduction in systemic inflammatory response after challenge when compared to unvaccinated controls [68]. In adult and newborn C57BL/6 mice MTBVAC confers significantly greater protection than BCG SSI as measured by significant CFU reduction (>0.5 log) in lung bacterial burden [39,71]. Of note, in the well-established guinea pig model at PHE, BCG is given at a lower 5×10 4 CFU dose, and in those studies MTBVAC and SO2 administration normally followed the same vaccination regimen as that of BCG to allow for data comparison.…”

Section: Protective Efficacy and Immunogenicity Of Mtbvac And Prototymentioning

confidence: 99%

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MTBVAC from discovery to clinical trials in tuberculosis-endemic countries

Marinova

Gonzalo-Asensio

Aguilo

et al. 2017

Expert Review of Vaccines

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Introduction: BCG remains the only vaccine against tuberculosis (TB) in use today and despite its impressive global coverage, the nature of BCG protection against the pulmonary forms of TB remains subject to ongoing debate. Because of the limitations of BCG, novel TB vaccine candidates have been developed and several have reached the clinical pipeline. One of these candidates is MTBVAC, the first and only TB vaccine in the clinical pipeline to date based on live-attenuated Mycobacterium tuberculosis that has successfully entered clinical evaluation, a historic milestone in human vaccinology. Areas covered: This review describes development of MTBVAC from discovery to clinical development in high burden TB-endemic countries. The preclinical experiments where MTBVAC has shown to confer improved safety and efficacy over BCG are presented and the clinical development plans for MTBVAC are revealed. The search of all supportive literature in this manuscript was carried out via Pubmed. Expert commentary: Small experimental medicine trials in humans and preclinical efficacy studies with a strong immunological component mimicking clinical trial design are considered essential by the scientific community to help identify reliable vaccine-specific correlates of protection in order to support and accelerate community-wide efficacy trials of new TB vaccines. ARTICLE HISTORY

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Section: Preclinical Characterization Of Mtbvacmentioning

confidence: 80%

Section: Protective Efficacy and Immunogenicity Of Mtbvac And Prototymentioning

confidence: 90%

Section: Protective Efficacy and Immunogenicity Of Mtbvac And Prototymentioning

confidence: 99%

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MTBVAC from discovery to clinical trials in tuberculosis-endemic countries

Marinova

Gonzalo-Asensio

Aguilo

et al. 2017

Expert Review of Vaccines

Self Cite

View full text Add to dashboard Cite

show abstract

“…Others have developed attenuated M. tuberculosis and, indeed, one is based on two independent stable deletion mutations in the virulence genes phoP and fadD26 and is in clinical trials [21]. The current study examined the use, as a vaccine, of an M. tuberculosis mutant in which the sigE gene was disrupted.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis sigE mutant ST28 used as a vaccine induces protective immunity in the guinea pig model

et al. 2017

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With more than 9 million new infections and 1.5 million deaths claimed every year, tuberculosis remains one of the major scourges of humankind. The only vaccine available against this disease, the attenuated strain Mycobacterium bovis, BCG is effective against severe forms of the disease in infants, but scarcely effective in protecting adults from the pulmonary form of the disease, thus not stopping transmission. Consequently, the development of an effective anti-tuberculosis vaccine is a major goal for improving global health. The most common concept is that a more effective vaccine should include a first immunization with a live vaccine followed by the administration of an acellular boosting vaccine. In this approach, the live vaccine might be either BCG or a different, more efficient attenuated strain. Recently, we showed that a Mycobacterium tuberculosis mutant missing the gene encoding for the extracellular function sigma factor SigE, is strongly attenuated and is able to induce a more effective protection from M. tuberculosis infection compared to BCG in mice. We now further characterize the protective potential of this novel strain in the guinea pig model of tuberculosis. In the guinea pig, it had limited growth but induced a Th1 immune response and was able to significantly reduce the number of colony forming units as well as prolong survival. Taken together these data provide evidence for the use of the M. tuberculosis sigE mutant as the basis for further development as a vaccine against infection.

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“…Moreover, this vaccine has the important advantage to target antigens expressed during early M. tb infection. Interestingly, the MTBVAC vaccine has demonstrated improved protection compared to BCG in adult and newborn animal models . In clinical phase 1, this vaccine demonstrated comparable safety to BCG .…”

Section: Introductionmentioning

confidence: 99%

Current challenges and opportunities for bacillus Calmette‐Guérin replacement vaccine candidates

Méndez-Samperio¹

2019

Scand J Immunol

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Bacillus Calmette‐Guérin (BCG) remains the only licensed vaccine against human tuberculosis (TB). BCG is a live‐attenuated strain of Mycobacterium bovis, with limitations in efficacy against respiratory TB, the most common form of the disease responsible for transmission. However, continues to be used in the immunization programmes of different countries in the absence of another alternative. In order to improve BCG efficacy against pulmonary TB, in the current clinical TB vaccine pipeline, there are live‐attenuated TB vaccines to replace BCG. This review discusses the current status of the development of live vaccine candidates designed to replace BCG from the rational strategies and immunological challenges to its clinical trial and identify key areas in the next years considered essential to confer improved safety and efficacy over BCG.

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MTBVAC vaccine is safe, immunogenic and confers protective efficacy against Mycobacterium tuberculosis in newborn mice

Cited by 49 publications

References 17 publications

MTBVAC from discovery to clinical trials in tuberculosis-endemic countries

MTBVAC from discovery to clinical trials in tuberculosis-endemic countries

Mycobacterium tuberculosis sigE mutant ST28 used as a vaccine induces protective immunity in the guinea pig model

Current challenges and opportunities for bacillus Calmette‐Guérin replacement vaccine candidates

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