Safety and Immunogenicity of the Recombinant Mycobacterium bovis BCG Vaccine VPM1002 in HIV-Unexposed Newborn Infants in South Africa (original) (raw)

Mycobacterium tuberculosis & its recent vaccine approach: A review

In this review, we argue current advancement in the improvement, recent researches, general manifestation, epidemiology, global TB control program, pathogenesis, clinical features, diagnosis, treatment, risk factors and prevention. In excess of the last 24 years, incredible evolution has been made in TB vaccine research and expansion: In adding up inventive approaches are being pursued to more develop accessible vaccines, as well as discover fresh ones. Thus, there is superior reason for confidence in the field of TB vaccines that it will be probable to build up better vaccines than BCG. Because this BCG vaccine has certain issues which need to be addressed. BCG vaccine has a little impact on the pulmonary TB, means the disease is still transmissible and also the protective ability of BCG against pulmonary TB in adults is incomplete and inconsistent. Another issue of concern that compromises BCG's utility is that infants with HIV have an increased risk of developing disseminated...

Immune Responses Following BCG Immunization of Infants in Uganda and United Kingdom Are Similar for Purified Protein Derivative but Differ for Secretory Proteins of Mycobacterium tuberculosis

Frontiers in Immunology

Introduction:The immunogenicity of BCG vaccination in infants differs between populations. We hypothesized that prenatal exposure to mycobacterial antigens might explain the differences in immune responses to BCG seen in other studies of infants in Africa and the United Kingdom (UK) and we explored this in birth cohorts in Uganda and the UK.Materials and Methods:Blood samples were obtained from BCG-immunized infants of mothers with (n= 110) and without (n= 121) latentMycobacterium tuberculosisinfection (LTBI) in Uganda and BCG-immunized infants of mothers without LTBI (n= 25) in the UK at 10 and 52 weeks after birth. Cytokine and chemokine responses to PPD were measured to assess responses to BCG immunization, and to ESAT6/CFP10 to assess exposure to or infection withM. tuberculosisor non-tuberculous mycobacteria (NTM) in 6-day whole blood culture supernatants by a 17-plex Luminex assay. Median responses were compared between Ugandan infants (together, and separated by maternal LTBI...

Natural Variation in Immune Responses to Neonatal Mycobacterium bovis Bacillus Calmette-Guerin (BCG) Vaccination in a Cohort of Gambian Infants

PLoS ONE, 2008

Background: There is a need for new vaccines for tuberculosis (TB) that protect against adult pulmonary disease in regions where BCG is not effective. However, BCG could remain integral to TB control programmes because neonatal BCG protects against disseminated forms of childhood TB and many new vaccines rely on BCG to prime immunity or are recombinant strains of BCG. Interferon-gamma (IFN-c) is required for immunity to mycobacteria and used as a marker of immunity when new vaccines are tested. Although BCG is widely given to neonates IFN-c responses to BCG in this age group are poorly described. Characterisation of IFN-c responses to BCG is required for interpretation of vaccine immunogenicity study data where BCG is part of the vaccination strategy.

A Replication-Limited Recombinant Mycobacterium bovis BCG Vaccine against Tuberculosis Designed for Human Immunodeficiency Virus-Positive Persons Is Safer and More Efficacious than BCG

Infection and Immunity, 2008

Tuberculosis is the leading cause of death in AIDS patients, yet the current tuberculosis vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), is contraindicated for immunocompromised individuals, including human immunodeficiency virus-positive persons, because it can cause disseminated disease; moreover, its efficacy is suboptimal. To address these problems, we have engineered BCG mutants that grow normally in vitro in the presence of a supplement, are preloadable with supplement to allow limited growth in vivo, and express the highly immunoprotective Mycobacterium tuberculosis 30-kDa major secretory protein. The limited replication in vivo renders these vaccines safer than BCG in SCID mice yet is sufficient to induce potent cell-mediated and protective immunity in the outbred guinea pig model of pulmonary tuberculosis. In the case of one vaccine, rBCG( mbtB )30, protection was superior to that with BCG (0.3-log fewer CFU of M. tuberculosis in the lung [ P < 0.04] and 0...

Novel Human In Vitro System for Evaluating Antimycobacterial Vaccines

Infection and Immunity, 2004

Major research efforts are directed towards the development of a better antimycobacterial vaccine. But progress in the field of tuberculosis vaccine development has been hampered by the lack of human in vitro models to assess vaccine immunogenicity and efficacy. New candidate vaccines will have to be evaluated against the existing Mycobacterium bovis BCG “gold standard.” It is therefore important to understand the type of immune responses elicited by BCG vaccination to enable comparisons with potential new candidates. We used a novel human in vitro whole-blood model, which measures immune responses to mycobacteria by use of reporter gene-tagged BCG (BCG lux), to study immune responses to BCG vaccination in 50 neonates in a setting in Cape Town, Republic of South Africa, where tuberculosis is endemic. BCG vaccination significantly reduced growth of BCG lux in whole blood (prevaccination median growth ratio [GR], 9.6; range, 1.3 to 24; postvaccination median GR, 3.9; range, 0.6 to 12....