Efficacy of BCG vaccine in animal models of neurological disorders

Cossu, Davide; Ruberto, Stefano; Yokoyama, Kazumasa; Sechi, Leonardo Antonio

doi:10.1016/j.vaccine.2021.12.005

Cited by 8 publications

(4 citation statements)

References 55 publications

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“…For example, the influenza vaccine reduces cerebrovascular events, a known risk factor for dementia ( 52 , 53 ); the herpes zoster vaccine prevents reactivation of herpes virus in the brain; and intravesical BCG instillation significantly increases serum IL-2 levels, which leads to an expansion of the number of neuroprotective Treg cells ( 54 , 55 ). In fact, previous studies have also shown that influenza and BCG vaccines in animal models can enhance and maintain microglia activation, restore brain immune homeostasis and reduce Aβ burden, ultimately improving cognitive impairment ( 56 , 57 ). It is therefore possible that these vaccines have preventive benefits by intervening in the pathological process of dementia.…”

Section: Discussionmentioning

confidence: 99%

Adult Vaccination as a Protective Factor for Dementia: A Meta-Analysis and Systematic Review of Population-Based Observational Studies

He²,

Xia

et al. 2022

Front. Immunol.

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BackgroundCommon vaccinations may have impacts on dementia risk, but current evidence is inconsistent. We therefore investigated the association between vaccinations and dementia risk by systematic review and meta-analysis approach.MethodsWe conducted an extensive search of PubMed, Embase, Cochrane Library, and Web of Science to identify studies that compared the risk of dementia in vaccinated versus unvaccinated populations. The adjusted hazard ratio (HR) and corresponding 95% confidence intervals (CIs) were pooled as measures.ResultsOf the 9124 records initially retrieved, 17 studies with 1857134 participants were included in our analysis. The overall pooled results showed that vaccinations were associated with a 35% lower dementia risk (HR=0.65, 95% CI: 0.60-0.71, Poverall effect < 0.001; I2 =91.8%, Pheterogeneity<0.001). All types of vaccination were associated with a trend toward reduced dementia risk, with rabies (HR=0.43), tetanus & diphtheria & pertussis (Tdap) (HR=0.69), herpes zoster (HR=0.69), influenza (HR=0.74), hepatitis A (HR=0.78), typhoid (HR=0.80), and hepatitis B (HR=0.82) vaccinations being significant. Individuals with more full vaccination types and more annual influenza vaccinations were less likely to develop dementia. Gender and age had no effect on this association.ConclusionRoutine adult vaccinations are associated with a significant reduction in dementia risk and may be an effective strategy for dementia prevention. Further research is needed to elucidate the causal effects of this association and the underlying mechanisms.

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Section: Discussionmentioning

confidence: 99%

Adult Vaccination as a Protective Factor for Dementia: A Meta-Analysis and Systematic Review of Population-Based Observational Studies

He²,

Xia

et al. 2022

Front. Immunol.

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“…Based on the reports for BCG and neurodegenerative diseases, its strain and dose-dependent mechanism of action, related to modulation of peripheral and CNS immune components, are primarily responsible for its neuroprotective effect. 48 Accordingly, in this study, we investigated changes in the levels of the immune factors as well as their effects on dendritic morphology in APP/PS1 mice after BCG immunization. Thus, we observed an increase in the IFN-γ and IL-4 levels, regarded as neurotrophic factors, and a decrease in the TNF-α level in both the serum and hippocampus of APP+BCG mice, relative to the control mice; changes were more pronounced in the APP +3BCG group.…”

Section: Discussionmentioning

confidence: 99%

Changes in dendritic complexity and spine morphology following BCG immunization in APP/PS1 mice

Li¹,

Wang²,

Wang³

et al. 2022

Human Vaccines & Immunotherapeutics

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Bacillus Calmette – Guerin (BCG) is an immune regulator that can enhance hippocampal synaptic plasticity in rats; however, it is unclear whether it can improve synaptic function in a mouse model with Alzheimer’s disease (AD). We hypothesized that BCG plays a protective role in AD mice and investigated its effect on dendritic morphology. The results obtained show that BCG immunization significantly increases dendritic complexity, as indicated by the increased number of dendritic intersections and branch points, as well as the increase in the fractal dimension. Furthermore, the number of primary neurites and dendritic length also increased following BCG immunization, which increased the number of spines and promoted maturation. IFN-γ and IL-4 levels increased, while TNF-α levels decreased following BCG immunization; expression levels of p -JAK2, P-STAT3, SYN, and PSD-95 also increased. Therefore, this study demonstrates that BCG immunization in APP/PS1 mice mitigated hippocampal dendritic spine pathology, especially after the third round of immunization. This effect could possibly be attributed to; changes in dendritic arborization and spine morphology or increases in SYN and PSD-95 expression levels. It could also be related to mechanisms of BCG-induced increases in IFN-γ or IL-4/JAK2/STAT3 levels.

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“…On the other hand, studies in animal models have shown that different types of Bacillus Calmette-Guerin vaccine can confer non-specific neuroprotection and therapeutic benefits in PD by inducing specific regulatory T (Treg) responses and reducing microglia proliferation and activation [104]. Interestingly, rifampin, an antibiotic used for the treatment of mycobacterial infections, can inhibit microglial inflammation and neurodegeneration induced by α-syn fibrillary aggregates [105].…”

Section: Gut Microbiota Infections and Mitochondrial Dysfunction In Pdmentioning

confidence: 99%

The Role of Immune Dysfunction in Parkinson’s Disease Development

Cossu,

Hatano,

Hattori

2023

IJMS

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Recent research has unveiled intriguing insights suggesting that the body’s immune system may be implicated in Parkinson’s disease (PD) development. Studies have observed disparities in pro-inflammatory and anti-inflammatory markers between PD patients and healthy individuals. This finding underscores the potential influence of immune system dysfunction in the genesis of this condition. A dysfunctional immune system can serve as a primary catalyst for systemic inflammation in the body, which may contribute to the emergence of various brain disorders. The identification of several genes associated with PD, as well as their connection to neuroinflammation, raises the likelihood of disease susceptibility. Moreover, advancing age and mitochondrial dysfunction can weaken the immune system, potentially implicating them in the onset of the disease, particularly among older individuals. Compromised integrity of the blood–brain barrier could facilitate the immune system’s access to brain tissue. This exposure may lead to encounters with native antigens or infections, potentially triggering an autoimmune response. Furthermore, there is mounting evidence supporting the notion that gut dysbiosis might represent an initial trigger for brain inflammation, ultimately promoting neurodegeneration. In this comprehensive review, we will delve into the numerous hypotheses surrounding the role of both innate and adaptive immunity in PD.

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Efficacy of BCG vaccine in animal models of neurological disorders

Cited by 8 publications

References 55 publications

Adult Vaccination as a Protective Factor for Dementia: A Meta-Analysis and Systematic Review of Population-Based Observational Studies

Adult Vaccination as a Protective Factor for Dementia: A Meta-Analysis and Systematic Review of Population-Based Observational Studies

Changes in dendritic complexity and spine morphology following BCG immunization in APP/PS1 mice

The Role of Immune Dysfunction in Parkinson’s Disease Development

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