BCG Vaccine Trains Innate Immunity

Highlights

• Researchers studied the mechanism of action of BCG vaccine to understand the factors that contributed better immunity against infections.
• The BCG vaccine was found to induce //metabolic changes that included changes to DNA methylation that affected innate immunity.
• This study dispels earlier belief that innate immunity could not provide long term immunity.
• Further drug therapies and vaccines could be designed that work on similar principles of trained innate immunity.

The vaccine for tuberculosis, Bacillus Calmette-Guerin, is known to protect against other infectious diseases and even cancer. It is one of the most widely used vaccine and is found to be effective against multiple infections due to trained immunity in white blood cells where metabolic and epigenetic changes are carried out. Tuberculosis is caused by the bacteria Mycobacterium tuberculosis and is characterized by infection of the lung. The initial infection may be contained by the host’s immune response but when the host’s immune system is weakened due to other infections, like HIV infection or underlying factors in the host’s body, there is a return of infection.

Researchers are now trying to understand the mechanism of action of BCG vaccine to enable immunological and metabolic stimulation which would increase the effectiveness of other vaccines.

Radboud University Medical Center’s Mihai Netea who is also the senior author of the study said "The implications of these findings are double: On the one hand, we have uncovered new biological interactions that link cellular metabolism with immune responses, and on the other hand, we have opened the door for new therapeutic approaches in which metabolism modulators modulate innate immune responses and can serve as potential novel immunotherapies. However, what it is important to realize is that this is the beginning of the process to bring this to clinical practice, and more studies are needed for that."

BCG Vaccine
The BCG vaccine is made from a form of bacteria that closely resembles the TB bacteria. The vaccine provides 70 to 80% protection against TB infections, including TB meningitis. In India, BCG vaccine is administered to all infants.

• Found to protect against lower respiratory tract infections leading to lowered mortality.
• Used in the treatment of bladder cancer
• Effective against asthma
• Used against parasitic infections

Mechanism
Netae and colleagues served to understand the mechanism of action of the BCG vaccine by studying the metabolic changes induced by the vaccine in monocytes. The researchers found that

• There was a long lasting effect on glycolysis and to a lower level, on glutamine metabolism.
• The change from glucose metabolism to glycolysis was required for the BCG induced trained immunity.
• These changes are mediated via epigenetic mechanism where there is no change in the gene.
• Such changes aid in increasing the ability of the innate immune system to mount an effective immune response to pathogens.
• The metabolic changes induced by the BCG vaccine were necessary for histone modification.

In humans, the gene variations that were responsible for glycolysis enzymes lead to innate immunity in monocytes being affected. The metabolic changes induced by the BCG vaccine resulted in trained immunity.

Adaptive Innate Immune System
Scientists had long believed that the innate immune system could not be adapted to provide long term immunity on exposure to pathogens or vaccinations. However, this study showed that BCG could alter metabolic processes which resulted in adaptive innate immunity. This was the acquired immunity that was believed to provide long term immune response against pathogens or vaccines.

Host Immune Response
When a pathogen enters the human body, the body responds with a swift but non-specific immune response called the innate immune response. The acquired immune response acts after a period of time but it is specific and the memory of the pathogen is retained for long term immunity.

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The study by Netea and colleagues has shown that the innate immunity could be trained using the BCG vaccine. An understanding of this mechanism can be used in the development of other vaccines for better protection.

BCG Vaccine in Cancer Therapy
Previous studies have shown that the BCG vaccine is effective as a treatment for bladder cancer. It protects the lining of the bladder and is found to lower the risk of the cancer becoming invasive.

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The BCG vaccine will be provided for 6 weeks and then there will be a break for 6 weeks. The vaccine is then provided every week with a gap of 1 to 3 weeks.

The effectiveness of this vaccine against a host of infections and certain forms of cancer is indicative of the effective mechanism adopted by the vaccine. A good understanding of the mechanism will aid in understanding the intricacies of the immune system and its ability to mount an effective innate immune response.

Studies show that the BCG vaccine is underestimated and that it has a lot more potential benefits in the treatment of infections than has been documented. Earlier studies showed that BCG vaccine was effective against many tuberculosis infections but not against infection by TB bacteria. However, later studies showed that the BCG vaccine was effective against a host of infections caused by the TB bacteria, including TB meningitis.

References

1. BCG treatment for early (non-invasive) bladder cancer - http://www.macmillan.org.uk/cancerinformation/cancertypes/bladder/treatingearly/bcgtreatment.aspx)
2. International study suggests benefits of TB vaccine have been underestimated - http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_15-8-2012-14-11-37)
3. BCG Vaccine – Current use, safety & skin test - http://www.tbfacts.org/bcg-tb-vaccine/)

Source-Medindia