The second Geneva Consensus: Recommendations for novel live TB vaccines (original) (raw)
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Vaccine, 2010
The current World Health Organization Requirements for BCG vaccine are in need of revision to address the diversity of sub-strains used for production, potential improvements of quality control assays for lot release, and the establishment of sub-strain specific Reference Reagents. A consultation meeting was organized to discuss issues regarding the standardization and evaluation of BCG vaccines in the forum of regulators, BCG vaccine manufacturers, developers of selected new live tuberculosis (TB) vaccines and researchers. The development of new recombinant BCG and live attenuated TB vaccines and the characterisation of different BCG sub-strains using state-of-the-art technologies were also reviewed. The objective of the meeting was to revise and update the current recommendations focused on the scope, terminology, manufacturing issues, and the incorporation of new reference reagents and new quality control tests.
Expert Opinion on Biological Therapy, 2012
Introduction: Apart from better diagnostics and new anti-microbial drugs, an effective vaccine for tuberculosis is urgently needed to halt this poverty-related disease, afflicting millions of people worldwide. Areas covered: After a general introduction on the global threat of tuberculosis, the pros and cons of the existing M. bovis BCG vaccine are discussed. As the correlates of protection against tuberculosis remain largely unknown, new findings in biomarker research are described. Next, an update on the ongoing Phase I and Phase II clinical trials is given. Finally, some of the most promising novel pre-clinical developments using live attenuated vaccines, sub-unit vaccines, prime-boost strategies, and new vaccination routes are discussed. The field has made considerable progress and 12 vaccine candidates have now actually entered Phase I or Phase IIa and IIb clinical trials. Expert opinion: It is argued that the variable protection conferred by the existing BCG vaccine against reactivation of latent TB is caused not only by waning of its efficacy with time but also by its weak induction of MHC class I restricted responses. Prime-boost strategies based on the actual BCG vaccine may not be sufficient to overcome this hurdle. The use of plasmid DNA vaccination might offer a solution.
Tuberculosis vaccine: A journey from BCG to present
Life Sciences, 2020
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An Update on Tuberculosis Vaccines
Vaccine Design, 2021
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a leading cause of mortality and morbidity due to a single infectious agent. Aerosol infection with Mtb can result in a range of responses from elimination, active, incipient, subclinical, and latent Mtb infections (LTBI), depending on the host's immune response and the dose and nature of infecting bacilli. Currently, BCG is the only vaccine approved to prevent TB. Although BCG confers protection against severe forms of childhood TB, its use in adults and those with comorbid conditions, such as HIV infection, is questionable. Novel vaccines, including recombinant BCG (rBCG), were developed to improve BCG's efficacy and use as an alternative to BCG in a vulnerable population. The first-generation rBCG vaccines had different Mtb antigens and were tested as a prime, prime-boost, or immunotherapeutic intervention. The novel vaccines target one or more of the following requirements, namely prevention of infection (POI), prevention of disease (POD), prevention of recurrence (POR), and therapeutic vaccines to treat a TB disease. Several vaccine candidates currently in development are classified into four primary categories: live attenuated whole-cell vaccine, inactivated whole-cell vaccine, adjuvanted protein subunit vaccine, and viral-vectored vaccine. Each vaccine's immunogenicity, safety, and efficacy are tested in preclinical animal models and further validated through various phases of clinical trials. This chapter summarizes the various TB vaccine candidates under different clinical trial stages and promises better protection against TB.
Live recombinant vaccines against tuberculosis that are safer and more potent than BCG
SciELO Public Health
Our approach to an improved replacement vaccine for BCG is the development of live recombinant BCG vaccines overexpressing key immunoprotective proteins of Mycobacterium tuberculosis (Mtb). As a vector, BCG advantages include wellestablished safety, a baseline level of protective efficacy, high acceptability worldwide, and an intracellular lifestyle and antigen presentation pathway similar to Mtb. We have previously described rBCG30, the first recombinant BCG vaccine against TB and the first vaccine more potent than BCG. rBCG30 overexpresses the Mtb 30-kDa major secretory protein (Antigen 85B; r30). In the demanding guinea pig model, rBCG30-immunized animals survived significantly longer than BCGimmunized animals after Mtb aerosol challenge, and, in 18 consecutive experiments, had significantly fewer Mtb in the lung (mean 0.8 0.1 log CFU less) and spleen (mean 1.1 0.1 log CFU less). In a Phase 1 human trial, rBCG30 was as welltolerated as BCG and, in contrast to BCG, induced significantly increased Antigen 85B-specific immune responses. To render rBCG30 safe for HIV-positive persons, who suffer disproportionately from tuberculosis but in whom BCG can disseminate, we engineered rBCG(mbtB)30, a recombinant BCG vaccine that overexpresses r30 and is mycobactin/exochelindependent, rendering it defective in iron acquisition and hence growth-limited in vivo. If preloaded with iron, rBCG(mbtB)30 can multiply several times in vivo, sufficient to induce strong immune responses but not to disseminate. In the guinea pig model, rBCG(mbtB)30 is significantly more potent than BCG; in SCID mice, rBCG(mbtB)30 is much safer than BCG. These studies demonstrate the feasibility of vaccines that are concurrently more potent and safer than BCG. Research and development of new generation of live vaccines against Tuberculosis