Potential health effects from non‐specific stimulation of the immune function in early age: The example of BCG vaccination

Abstract

There is increasing, but still inconsistent evidence that vaccinations and childhood infections may play a role in the normal maturation of the immune system, and in the development and balance of immune regulatory pathways, both of which might impact health later in life. This review covers the epidemiological evidence regarding the role of Bacillus Calmette-Guérin (BCG) vaccination on the following inflammatory or autoimmune diseases: asthma and allergic diseases, Crohn's disease (CD), insulin-dependent diabetes mellitus (IDDM), and specific cancers. The literature is more comprehensive for asthma and allergic diseases, with 16 studies reporting the absence of an association while seven rather suggest a protective effect of BCG. We found insufficient evidence on CD to conclude at this point. Overall, the evidence for IDDM based on four studies leans towards no association, although some effects were observed in population subsets. Five epidemiological investigations provide evidence on a possible link with cancer incidence or mortality at various sites, with indications of both increased and decreased risks. Given the potential public health implications, it is imperative to acquire a better understanding of how BCG vaccination could influence the development of such chronic health conditions in the population.

Early Vaccinations Are Not Risk Factors for Celiac Disease

“…[29][30][31][32] On the contrary, previous studies on BCG and T1D found no association, 27,33 but the evidence remains inconsistent. 34 In our study, BCG vaccination was significantly associated with decreased risk for CD (adjusted OR 0.54), but with no difference between girls and boys. Referents received BCG at a younger age, which could indicate that to exert a protective effect, BCG has to be given early in life.…”

Immunometabolic Pathways in BCG-Induced Trained Immunity

“…Furthermore, in two randomized controlled trials, early administration of the BCG vaccination reduced child mortality, mainly as a result of less neonatal sepsis and lower respiratory infections (Aaby et al., 2011, Biering-Sørensen et al., 2012, Kristensen et al., 2000). BCG is also used to treat bladder cancer and appears to be beneficial in treating several other diseases or conditions, such as warts, leishmaniasis, and asthma (Pereira et al., 2009, Rousseau et al., 2008, Salem et al., 2013). As further proof of its non-specific protective effects, BCG was shown to protect mice against lethal candidiasis (van ’t Wout et al., 1992), and, interestingly, this protective effect was also present in SCID (severe combined immunodeficiency) mice, therefore showing that this non-specific protection is T and B cell independent (Kleinnijenhuis et al., 2012).…”

BCG vaccination and allergy: A systematic review and meta-analysis

“…This is because BCG has a T H 1 stimulatory effect, which results in it altering cytokine response patterns in such a way that the T H 2 immunologic response is inhibited, thus antagonizing atopy, as has now been demonstrated both in animal models and human subjects. 12 On this basis, it has been suggested that BCG vaccination administered in infancy might have a protective effect against the development of atopic diseases. 13 Randomized controlled trials (RCTs) are the only study design to allow the effectiveness of interventions to be reliably assessed.…”