Prospects in Mycobacterium bovis Bacille Calmette et Guérin (BCG) vaccine diversity and delivery: Why does BCG fail to protect against tuberculosis?

Moliva, Juan I.; Turner, Joanne; Torrelles, Jordi B.

doi:10.1016/j.vaccine.2015.08.033

Cited by 80 publications

(72 citation statements)

References 89 publications

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“…These antigens are constituents of some of the most clinically advanced subunit vaccines in the pipeline to date [2,3], designed to boost BCG-induced immunity at birth mainly in adolescents and adults [78]. Ag85B was expressed in the recombinant BCG, rBCG30, demonstrating improved efficacy in guinea pigs over BCG [79].…”

Section: Protective Efficacy and Immunogenicity Of Mtbvac And Prototymentioning

confidence: 99%

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: Protective Efficacy and Immunogenicity Of Mtbvac And Prototymentioning

confidence: 99%

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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“…In developing countries, TB infection still constitutes a major public health problem among children. Even if, great improvement has been done to improve TB immunization, the challenge remains still the same (Moliva 2015). In fact, the protective efficacy of BCG and its duration varies significantly according to geography and population age (Moliva 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Even if, great improvement has been done to improve TB immunization, the challenge remains still the same (Moliva 2015). In fact, the protective efficacy of BCG and its duration varies significantly according to geography and population age (Moliva 2015). Many new vaccines seek to improve upon BCG using genetic modifications, and although new vaccines are in development there remain several challenges to implementing them worldwide (Moliva 2015).…”

Section: Introductionmentioning

confidence: 99%

“…In fact, the protective efficacy of BCG and its duration varies significantly according to geography and population age (Moliva 2015). Many new vaccines seek to improve upon BCG using genetic modifications, and although new vaccines are in development there remain several challenges to implementing them worldwide (Moliva 2015). Tremendous progress in improving vaccination coverage has been made over the past four decades in many African countries (WHO 2005; (Lakew 2015).…”

Section: Introductionmentioning

confidence: 99%

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Co-administration of Oal Polio Vaccine and Bacillus Calmette Guerin in Infants: Systematic Review of Low and Middle-income Countries

Tamuzi¹,

Muyaya²,

Tshimwanga³

2017

IAM

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Background: Immunization decreases 2 to 3 million deaths annually; however, an additional 1.5 million deaths could be avoided if global vaccination coverage improves. Immunization is one of the cornerstone interventions to reach the Millennium Development Goals (MDGs), especially the goal to decrease deaths among children under five years old. Childhood vaccinations have been illustrated to be effective in protecting children against vaccine preventable diseases in low and middle-income countries. As one of the earliest vaccines of the World Health Organization's (WHO) Expanded Program on Immunization established in 1974, Bacillus Calmette-Guérin (BCG) is the main stone of childhood vaccination. Administering OPV together with BCG might downregulate the response to BCG vaccine (Kaur 2002;Faridi 2015). Reviewing different studies, it has reported that this may downregulate response to BCG in the form of fewer numbers of scar formation, reduced scar size, reduced in vivo response to purified protein derivative (PPD) and significantly lower IL-13 and IFN-γ and a tendency to have lower IL-10 in response to PPD at 6 weeks following immunization. Objectives: To investigate whether co-administration of BCG and oral polio vaccine increased infant mortality rate.  To investigate whether co-administration of oral polio vaccine and BCG attenuate the immune response to BCG compared to the administration of BCG alone. Search methods: We searched through the following databases: MEDLINE, Register of Controlled Trials (CENTRAL); Scopus; CINAHL (EBSCO); Google Scholar; Clinicaltrials.gov and WHO International Clinical Trials Registry Platform (ICTRP). Main results: We found 1777 studies were through systematic electronic search. Therefore 1356 studies remained after excluding duplicated studies. We assessed and screened 855 studies, and only 11 articles were fully assessed. Among them, 6 studies were included in data analysis. There is high evidence that infant mortality rate was reduced by 22 % in BCG group compared to BCG-OPV group with a p-value of 0.09. Therefore, the evidence was moderate and low in specific mortality rate respectively boys and girls. Then, the mortality rate was reduced by 28% and 15 % respectively in boys and girls (p-value of 0.09 and 0.31). Local immune reaction (scar) was 41 % less likely present in BCG-OPV group compared to BCG alone. ). Therefore, the 95% CI is very wide and including the null value. Authors' Conclusions: An increasing number of vaccines targeting some of the leading causes of morbidity and mortality are reaching the world's children. Evidence suggests that receipt of BCG reduce overall infant mortality. This review has shown that co-administration BCG-OPV could increase infant mortality. Therefore, the results could be considered in a context of several limitations.

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“…It is a live M. bovis that has lost its virulence and has been widely used since 1945. However, the efficacy of BCG to protect against tuberculosis in humans has shown to be highly variable and dependent on different factors, such as the genetic of the subject population, environmental factors and the BCG substrain diversity [4]. In cattle, vaccination with BCG has demonstrated reductions in disease severity after experimental challenge with virulent M. bovis strains but the protection induced was, in general, not complete [5].…”

Section: Introductionmentioning

confidence: 99%