WHO Informal Consultation on standardization and evaluation of BCG vaccines Geneva, Switzerland 22–23 September 2009 (original) (raw)
Related papers
The second Geneva Consensus: Recommendations for novel live TB vaccines
Vaccine, 2010
Infection with Mycobacterium tuberculosis continues to be a major public health burden in most developing parts of the world and efforts to develop effective strategies for containing the disease remain a priority. It has long been evident that effective mass vaccination programmes are a cost effective and efficient approach to controlling communicable diseases in a public health setting and tuberculosis (TB) continues to be a major target. One approach with increasing acceptance is based upon on live mycobacterial vaccines, either as recombinant BCG or rationally attenuated M. tuberculosis, thus generating a new live TB vaccine. The Geneva Consensus published in March 2005 set out the opinion on priorities and requirements for developing live mycobacterial vaccines for Phase I trials. In the intervening period much progress has been made in both preclinical and clinical development of new TB vaccines and has provided the impetus for organising the second Geneva Consensus (held at WHO headquarters, April 2009) to discuss issues, including:
BCG Vaccine and New Tuberculosis Vaccines Against Mycobacterium tuberculosis: A review
2020
Mycobacterium tuberculosis (M. tuberculosis) causes tuberculosis (TB) which is a serious infectious disease. Bacteria are spread from person to person through tiny droplets released into the air via sneezing and coughing. Despite global efforts to control TB, the disease is the second most common cause of death after Acquired Immune Deficiency Syndrome (AIDS). Currently, Bacillus Calmette-Guerin (BCG) vaccine is used to prevent tuberculous meningitis and miliary disease, particularly in young children, but its protective efficacy is variable in adults. Therefore, there is an urgent need for the development of alternative TB vaccines. Recently, new TB vaccine development efforts have been advanced in different clinical studies. Most of these vaccines are live-attenuated or recombinant mycobacterium, live viral vector-based, and protein/adjuvant vaccines. This review explains the recapitulation of the current status of new TB vaccines updated with scientific literature references.
The influence of BCG vaccine strain on the immune response against tuberculosis: a randomised trial
The Bacille Calmette-Guérin (BCG) vaccine has been used for more than 80 years to protect against tuberculosis. Worldwide, over 90% of children are immunized with BCG, making it the most commonly administered vaccine, with more than 120 million doses used each year. Although new tuberculosis vaccines are under investigation, BCG will remain the cornerstone of the strategy to fight the worsening tuberculosis pandemic for the foreseeable future. The recent delineation of genetic differences between BCG vaccine strains has renewed interest in the influence of the vaccine strain on the protective efficacy against tuberculosis. This review critically examines the data from animal and human studies comparing BCG vaccine strains. Although there is good evidence to support the notion that the induced immune response and protection afforded against tuberculosis differs between BCG vaccine strains, currently, there are insufficient data to favour or recommend one particular strain. Identifying BCG strains with superior protection would have a dramatic effect on tuberculosis control at a population level: a small increment in protection provided by BCG immunization will prevent large numbers of cases of severe tuberculosis and deaths, particularly in children.
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
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.
Protection by BCG Vaccine Against Tuberculosis: A Systematic Review of Randomized Controlled Trials
Clinical Infectious Diseases, 2014
This new systematic review and analysis suggests BCG vaccination in infancy or BCG vaccination when stringent tuberculin testing excludes those with a small degree of prior infection or sensitization to environmental mycobacteria protects against pulmonary diseases even in the tropics Abstract Background: Randomized trials assessing BCG vaccine protection against tuberculosis have widely varying results, for reasons that are not well understood.
Influence of BCG vaccine strain on the immune response and protection against tuberculosis
FEMS microbiology reviews, 2008
The Bacille Calmette-Guérin (BCG) vaccine has been used for more than 80 years to protect against tuberculosis. Worldwide, over 90% of children are immunized with BCG, making it the most commonly administered vaccine, with more than 120 million doses used each year. Although new tuberculosis vaccines are under investigation, BCG will remain the cornerstone of the strategy to fight the worsening tuberculosis pandemic for the foreseeable future. The recent delineation of genetic differences between BCG vaccine strains has renewed interest in the influence of the vaccine strain on the protective efficacy against tuberculosis. This review critically examines the data from animal and human studies comparing BCG vaccine strains. Although there is good evidence to support the notion that the induced immune response and protection afforded against tuberculosis differs between BCG vaccine strains, currently, there are insufficient data to favour or recommend one particular strain. Identifyin...
The establishment of sub-strain specific WHO Reference Reagents for BCG vaccine
Vaccine, 2014
As the latest addition to the sub-strain specific WHO Reference Reagents of BCG vaccine, an international collaborative study was completed to evaluate the suitability of a candidate BCG Moreau-RJ sub-strain as a WHO Reference Reagent of BCG vaccine. This follows the recent replacement of the WHO 1st International Reference Preparation for BCG vaccine, by three sub-strain specific WHO Reference Reagents of BCG vaccine (Danish 1331, Tokyo 172-1 and Russian BCG-I) in order to complete the coverage of most predominant sub-strains used for BCG vaccine production and distribution for use worldwide. The study used cultural viable count and modified ATP assays to quantify the preparation and multiplex PCR to confirm the identity of the sub-strain. The establishment of this WHO Reference Reagent of BCG vaccine of Moreau-RJ sub-strain was approved by the WHO Expert Committee on Biological Standardization meeting in October 2012. This preparation is available for distribution by NIBSC-MHRA, U...