Tuberculosis (TB) remains a worldwide health problem, causing around 2 million deaths per year. Despite the bacillus Calmette Guerin vaccine being available for more than 80 years, it has limited effectiveness in preventing TB, with inconsistent results in trials. This highlights the urgent need to develop an improved TB vaccine, based on a better understanding of host-pathogen interactions and immune responses during mycobacterial infection. Recent studies have revealed a potential role for autophagy, an intracellular homeostatic process, in vaccine development against TB, through enhanced immune activation. This review attempts to understand the host innate immune responses induced by a variety of protein antigens from Mycobacterium tuberculosis, and to identify future vaccine candidates against TB. We focus on recent advances in vaccine development strategies, through identification of new TB antigens using a variety of innovative tools. A new understanding of the host-pathogen relationship, and the usefulness of mycobacterial antigens as novel vaccine candidates, will contribute to the design of the next generation of vaccines, and to improving the host protective immune responses while limiting immunopathology during M. tuberculosis infection.
Autophagy ; BCG Vaccine ; Host-Pathogen Interactions ; Immunity, Innate ; Mycobacterium tuberculosis ; Tuberculosis* ; Vaccines

BACKGROUND: Delivery of Bacille Calmette-Gurein (BCG) Tokyo vaccine, with the multipuncture device, has been much preferred over BCG Pasteur, with the intradermal method, possibly due to the easier manner of administration, a desire to avoid any trouble with scars, as well as side effects and higher profits to providers in South Korea. METHODS: To determine BCG scar status in 0~6 year old children vaccinated with two BCG vaccines (Pasteur BCG vaccine with intradermal method and BCG Tokyo vaccine with percutaneous method), the data from the national BCG scar survey in 2006 was analyzed. RESULTS: Based on the national survey, the high proportion that were vaccinated with BCG Tokyo vaccines with the multipuncture method (64.5%) was noted in 0~6 year old Korean children. From inspection of scar formation, as an indicator of vaccination, the median number of the visible pin scars from the percutaneous method was 16 (interquartile range, 12~18) in the Korean children, and pin scars decreased as the age of the children increased (p<0.001). CONCLUSION: The findings in this survey clearly showed a growing preference of parents for the BCG Tokyo vaccines by the multipuncture method in South Korea.
BCG Vaccine ; Child ; Cicatrix ; Humans ; Mycobacterium bovis ; Parents ; Republic of Korea ; Tokyo ; Tuberculosis ; Vaccination ; Vaccines

The anti-tuberculosis Bacille de Calmette et Guerin (BCG) vaccine was developed between 1905 and 1921 at Pasteur Institutes of Lille in France, and was adopted by many countries. BCG strains comprise natural mutants of major virulence factors of Mycobacterium tuberculosis and that BCG sub-strains differ markedly in virulence levels. The tuberculosis became endemic in Korea after the Korean War (1950s). The BCG strain, which was donated by Pasteur Institutes, was brought to Korea in 1955, and the first domestic BCG vaccine was produced by the National Defense Research Institute (NDRI), current Korea Centers for Disease Control and Prevention (KCDC), in 1960. Since 1987, BCG manufacture work was handed over to the Korean Institute of Tuberculosis (KIT), the freeze-dried BCG vaccine was manufactured at a scale required to meet the whole amount of domestic consumption. However, since 2006, the manufacture of BCG vaccine suspended and the whole amount of BCG was imported at this point of time. Now KIT is planning to re-produce the BCG vaccine in Korea under the supervision of KCDC, this will be render great role to National Tuberculosis Control Program (NTP) and provide initiating step for developing new tuberculosis vaccines in Korea.
Academies and Institutes ; BCG Vaccine ; Centers for Disease Control and Prevention (U.S.) ; France ; Hand ; Korea ; Korean War ; Mycobacterium bovis ; Mycobacterium tuberculosis ; Organization and Administration ; Sprains and Strains ; Tuberculosis ; Tuberculosis Vaccines ; Virulence Factors

PURPOSE: In the present study booster efficacies of Ag85 B, Bacillus Calmette-Guerin (BCG), and Ag85B peptides were evaluated using prime boost regimes in BALB/c mice. MATERIALS AND METHODS: Mice were primed with BCG vaccine and subsequently boosted with Ag85B, BCG and cocktail of Ag85B peptides. RESULTS: Based on analysis of immune response it was observed mice boosted with Ag85B peptides showed significant (p < 0.001) cytokines levels (interferon gamma, interleukin 12) and BCG specific antibodies (anti-BCG and anti-purified protein derivative titre) compared to booster dose of BCG, Ag85B and BCG alone. CONCLUSION: Our pilot results suggest that prime boost regimes with Ag85B peptides can boost waning BCG induced immunity and may improve immunogenicity of BCG vaccine. However, lot of work is further needed using experimental model of tuberculosis infection to justify the result.
Animals ; Antibodies ; Bacillus ; BCG Vaccine ; Cytokines ; Interleukins ; Mice* ; Models, Theoretical ; Mycobacterium bovis* ; Peptides* ; Pilot Projects* ; Tuberculosis ; Vaccines*

Tuberculosis (TB) is a serious infectious diseases threating human health, bacillus balmette-guerin vaccine (BCG) is the only available TB vaccine now, neonatal vaccination can significantly reduce the incidence and death of tuberculosis. However, due to its limited protection period, one dose vaccination after birth does not have a protective effect for adolescents and adults. Therefore, how to reduce the prevalence of TB in adolescents and adults effectively is essential for TB prevention and control. In this paper, we reviewed the literature from PubMed, CNKI, and Wanfang database to analyze and summarize the characteristics of BCG vaccine, immune effects and immunity endurance, the effects of BCG vaccination and repeated BCG vaccination in adolescents adults and discuse the change of attitude and trends of BCG use in the three documents issued by the World Health Organization on position of BCG.
Adolescent ; Adult ; Age Factors ; BCG Vaccine/immunology* ; Child ; Child, Preschool ; Humans ; Time Factors ; Tuberculosis/prevention & control* ; Tuberculosis Vaccines ; Vaccination ; World Health Organization

Recent studies show that the vector of recombinant Bacillus Calmette-Guérin (rBCG) has a series of advantages. With exogenous gene and vaccine in one inoculation, it can obtain strong and persistent immune response at one time so that BCG is considered as a kind of ideal vector for live recombinant vaccine. This review outlines the application of rBCG vaccine and its vector in infectious diseases caused by bacteria, viruses, other microorganisms and parasites.
AIDS Vaccines ; genetics ; immunology ; Antigens, Bacterial ; genetics ; immunology ; BCG Vaccine ; genetics ; immunology ; metabolism ; Communicable Disease Control ; methods ; Genetic Vectors ; genetics ; HIV Infections ; prevention & control ; HIV-1 ; Mycobacterium tuberculosis ; Recombinant Proteins ; biosynthesis ; genetics ; immunology ; Tuberculosis ; prevention & control ; Vaccines, Synthetic ; immunology

Tuberculosis (TB) is a contagious disease that has been responsible for the death of one billion people in the last 200 years. Until now, the only vaccine approved for the prevention of TB is Bacillus Calmette-Guérin (BCG), which is prepared by attenuating Mycobacterium bovis. However, one of the limitations of BCG is that its preventive effect against pulmonary TB varies from person to person. Therefore, there arises a need for a new TB vaccine to replace or supplement BCG. In this review, we have summarized the findings of current clinical trials on preventive and therapeutic TB vaccine candidates. In addition, we have discussed a novel vaccination approach using the cell-based vaccine presenting early secretory antigenic target-6 (ESAT-6), which is a potent immunogenic antigen. The role of ESAT-6 in hosts has also been described.
Bacillus ; Humans ; Mycobacterium bovis ; Tuberculosis* ; Vaccination ; Vaccines*

The best way to debunk a scientific dogma is to throw irrefutable evidence at it. This is especially true if the dogma in question has been nurtured over many decades, as is the case with the apparent redundancy of antibodies (Abs) against intracellular pathogens. Although not fully compelling yet, that ‘hard core’ evidence is nevertheless now slowly beginning to emerge. This is true for several clinically relevant infections but none more so than Mycobacterium tuberculosis, the archetype intracellular pathogen that poses a great health challenge to the mankind. Here, prompted by a spate of recent high-profile reports on the effects of Abs in various experimental models of tuberculosis, we step back and take a critical look at the progress that has been made in the last 5 years and highlight some of the strengths and shortcomings of the presented evidence. We conclude that the tide of the opinion has begun to turn in favour of Abs but we also caution against overinterpreting the currently available limited evidence. For, until definitive evidence that can withstand even the most rigorous of experimental tests is produced, the dogma may yet survive. Or indeed, we may find that the truth is hidden somewhere in between the dogma and the unfulfilled scientific prophecy.
Antibodies ; Immunotherapy ; Models, Theoretical ; Mycobacterium tuberculosis ; Tuberculosis ; Vaccines

Tuberculosis (TB) is the second leading infectious cause of mortality worldwide with about two million deaths per year. The only licensed TB vaccine, Mycobacterium bovis bacillus Calmette-Guerin (BCG) shows limited protection efficacy suggesting an improved vaccination strategy is required. Recently, several TB vaccine candidates have entered clinical trials. These vaccine candidates are live mycobacterial vaccines designed to replace BCG or subunit vaccines designed to boost immunity induced by BCG. Vaccines with different strategy such as therapeutic vaccines, which can also be used in combination with drug therapy, are in the early stages of development to resolve latent TB or reactivation from the latent state. In this review, we discuss about development of BCG and BCG-based vaccines and further studies necessary for novel TB vaccine development to sterilize tuberculosis.
Bacillus* ; Drug Therapy ; Mortality ; Mycobacterium bovis* ; Mycobacterium tuberculosis ; Tuberculosis* ; Vaccination ; Vaccines* ; Vaccines, Subunit

OBJECTIVETo review recent developments in therapeutic DNA vaccines against tuberculosis.

DATA SOURCESThe data used in this review were obtained mainly from the studies of therapeutic DNA vaccines against tuberculosis reported from 2000 to 2006.

STUDY SELECTIONRelevant articles about studies of therapeutic DNA vaccines against tuberculosis were selected.

DATA EXTRACTIONData were mainly extracted from the 32 articles listed in the reference section of this review.

RESULTSSome DNA vaccines which previously showed to induce protective immunity against infection by Mycobacterium tuberculosis in a prophylactic manner are also surprisingly effective when used therapeutically, including persistent Mycobacterium tuberculosis and multidrug-resistant tuberculosis which are refractory to immune system and antibacterial chemotherapy alone. When used in combination with antibacterial drugs, therapeutic DNA vaccines could effectively eliminate residual bacteria in infected animals and shorten the therapy course of conventional chemotherapy. Detailed studies demonstrated that therapeutic effects of DNA vaccines may at least partly be due to the restoration of the Th(1)/Th(2) balance. Some problems have also emerged along with these exciting results.

CONCLUSIONSTherapeutic DNA vaccine is a promising strategy against tuberculosis, however developing an ideal DNA vaccine for therapy of tuberculosis will require further development.