Genetic susceptibility to infections caused by BCG

Genetic Susceptibility to Infections Caused by BCG

Bacille Calmette-Guérin (BCG) is a vaccine primarily used against tuberculosis (TB). Despite its widespread use and efficacy in preventing severe forms of TB in children, there are instances where individuals, due to genetic susceptibility, develop infections following BCG vaccination. This article delves into the genetic factors that contribute to susceptibility to infections caused by BCG, highlighting the importance of understanding these genetic predispositions for improving vaccine safety and efficacy.

Background

BCG vaccine is derived from a strain of Mycobacterium bovis that is attenuated, meaning it has been modified to reduce its virulence while still stimulating an immune response in humans. Since its introduction in 1921, the BCG vaccine has been a cornerstone in the fight against TB, especially in countries with high prevalence of the disease. However, in a small number of cases, the vaccine can cause adverse reactions ranging from localized skin infections to more severe and disseminated infections, particularly in individuals with underlying immune deficiencies.

Genetic Factors

Research has identified several genetic factors that can increase an individual's susceptibility to infections following BCG vaccination. These factors are primarily related to genes involved in the immune response, including:

Interferon-Gamma Pathway

The Interferon-gamma (IFN-γ) pathway plays a crucial role in the immune response against mycobacterial infections. Mutations in genes associated with the IFN-γ pathway, such as IFNGR1, IFNGR2, STAT1, and IL12B, can lead to a condition known as Mendelian Susceptibility to Mycobacterial Diseases (MSMD). Individuals with MSMD are at a higher risk of developing infections after receiving the BCG vaccine.

IL-12/23-Interferon-Gamma Axis

The IL-12/23-Interferon-Gamma axis is another critical component of the immune response to mycobacteria. Genetic defects in this axis, including mutations in IL12RB1 and IL12B, result in impaired production of IFN-γ, further increasing the risk of adverse reactions to the BCG vaccine.

Other Genetic Factors

Additional genetic factors that may influence susceptibility to BCG-related infections include variations in the NEMO (NF-kappaB essential modulator) gene and other genes involved in the innate and adaptive immune responses. These genetic variations can lead to a broad range of immune deficiencies, making individuals more vulnerable to infections by attenuated pathogens like the BCG vaccine strain.

Clinical Implications

Understanding the genetic susceptibility to infections caused by BCG is crucial for identifying individuals at risk of adverse reactions to the vaccine. Genetic screening for known risk factors can help inform vaccination strategies, particularly in populations with a high prevalence of genetic immune deficiencies. Moreover, this knowledge can guide the development of alternative vaccination approaches for individuals with identified genetic risks.

Conclusion

While the BCG vaccine remains a vital tool in the global fight against tuberculosis, recognizing and understanding the genetic factors that contribute to susceptibility to infections following vaccination is essential. Continued research in this area will enhance our ability to safely and effectively use BCG and other live vaccines, ultimately improving public health outcomes.