Long-term effects of BCG vaccination on telomere length and telomerase activity.

This study explores the effects of Bacillus Calmette-Guérin (BCG) vaccination on telomere maintenance, an aging-related process, in immune cells. While BCG reduces systemic inflammation and enhances innate immune responsiveness by inducing trained immunity, its effects on other immune aging hallmarks, such as telomere shortening, are not fully understood. We assessed telomere length in two independent human cohorts before and three months after BCG vaccination.

Long-term DNA methylation changes mediate heterologous cytokine responses after BCG vaccination.

Background: Epigenetic reprogramming shapes immune memory in both innate (trained immunity) and adaptive immune cells following Bacillus Calmette-Guérin (BCG) vaccination. However, the role of dynamic DNA methylation changes in post-vaccination immune responses remains unclear.

Results: We established a cohort of 284 healthy Dutch individuals, profiling genome-wide DNA methylation and cytokine responses to ex vivo stimulation at baseline, 14 days, and 90 days post-BCG vaccination.

Seasonal variation in BCG-induced trained immunity.

The Bacille Calmette-Guerin (BCG) vaccine is a well-established inducer of innate immune memory (also termed trained immunity), causing increased cytokine production upon heterologous secondary stimulation. Innate immune responses are known to be influenced by season, but whether seasons impact induction of trained immunity is not known. To explore the influence of season on innate immune memory induced by the BCG vaccine, we vaccinated healthy volunteers with BCG either during winter or spring.

Determinants of Systemic SARS-CoV-2-Specific Antibody Responses to Infection and to Vaccination: A Secondary Analysis of Randomised Controlled Trial Data.

SARS-CoV-2 infections elicit antibodies against the viral spike (S) and nucleocapsid (N) proteins; COVID-19 vaccines against the S-protein only. The BCG-Corona trial, initiated in March 2020 in SARS-CoV-2-naïve Dutch healthcare workers, captured several epidemic peaks and the introduction of COVID-19 vaccines during the one-year follow-up. We assessed determinants of systemic anti-S1 and anti-N immunoglobulin type G (IgG) responses using trial data.

Alendronate modulates cytokine responses in healthy young individuals after BCG vaccination.

Bacillus Calmette-Guérin (BCG) vaccination induces memory characteristics in innate immune cells and their progenitors, a process called trained immunity mediated by epigenetic and metabolic reprogramming. Cholesterol synthesis plays an amplifying role in trained immunity through mevalonate release. Nitrogen-containing bisphosphonates (N-BPs), such as alendronate, can inhibit cholesterol synthesis.

MMR vaccination induces trained immunity via functional and metabolic reprogramming of γδ T cells.

The measles, mumps, and rubella (MMR) vaccine protects against all-cause mortality in children, but the immunological mechanisms mediating these effects are poorly known. We systematically investigated whether MMR can induce long-term functional changes in innate immune cells, a process termed trained immunity, that could at least partially mediate this heterologous protection. In a randomized, placebo-controlled trial, 39 healthy adults received either the MMR vaccine or a placebo.

Fatty acid desaturation and lipoxygenase pathways support trained immunity.

Infections and vaccines can induce enhanced long-term responses in innate immune cells, establishing an innate immunological memory termed trained immunity. Here, we show that monocytes with a trained immunity phenotype, due to exposure to the Bacillus Calmette-Guérin (BCG) vaccine, are characterized by an increased biosynthesis of different lipid mediators (LM) derived from long-chain polyunsaturated fatty acids (PUFA). Pharmacological and genetic approaches show that long-chain PUFA synthesis and lipoxygenase-derived LM are essential for the BCG-induced trained immunity responses of human monocytes.

The fungal-derived compound AM3 modulates pro-inflammatory cytokine production and skews the differentiation of human monocytes.

The proper functioning of the immune system depends on an appropriate balance between pro-inflammation and anti-inflammation. When the balance is disrupted and the system is excessively biased towards inflammation, immune responses cannot return within the normal range, which favors the onset of diseases of autoimmune or inflammatory nature. In this scenario, it is fundamental to find new compounds that can help restore this balance and contribute to the normal functioning of the immune system in humans.

Peripheral T Cell Populations are Differentially Affected in Familial Mediterranean Fever, Chronic Granulomatous Disease, and Gout.

Both innate errors of immunity, such as familial Mediterranean fever (FMF) and chronic granulomatous disease (CGD), and the common inflammatory disease gout are characterized by episodes of sterile inflammatory attacks in the absence of an infection. While these disorders encompass distinct pathologies due to differentially affected metabolic pathways and inflammasome activation mechanisms, their common features are the excessive production of interleukin (IL)-1ß and innate immune cell hyperreactivity. On the other hand, the role of T cells and innate-like lymphocytes such as gamma delta (γδ) T cells in these pathologies is ill-defined.

Evaluation of the safety and immunological effects of Bacillus Calmette-Guérin in combination with checkpoint inhibitor therapy in a patient with neuroendocrine carcinoma: a case report.

Background: Immune checkpoint inhibitors have revolutionized therapy of advanced and metastatic cancers. However, a significant proportion of patients do not respond to immune checkpoint inhibitors or develop resistance. Therefore, novel therapies or combinations of therapies that may act synergistically are needed.

Differences in Immune Responses in Individuals of Indian and European Origin: Relevance for the COVID-19 Pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic, large differences in susceptibility and mortality due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported between populations in Europe and South Asia. While both host and environmental factors (including Mycobacterium bovis BCG vaccination) have been proposed to explain this, the potential biological substrate of these differences is unknown. We purified peripheral blood mononuclear cells from individuals living in India and the Netherlands at baseline and 10 to 12 weeks after BCG vaccination.

The impact of BCG dose and revaccination on trained immunity.

The innate immune system can display heterologous memory-like responses termed trained immunity after stimulation by certain vaccinations or infections. In this randomized, placebo-controlled trial, we investigated the modulation of Bacille Calmette-Guérin (BCG)-induced trained immunity by BCG revaccination or high-dose BCG administration, in comparison to a standard dose. We show that monocytes from all groups of BCG-vaccinated individuals exerted increased TNFα production after ex-vivo stimulation with various unrelated pathogens.

Bacillus Calmette-Guérin vaccine to reduce healthcare worker absenteeism in COVID-19 pandemic, a randomized controlled trial.

Objectives: The COVID-19 pandemic increases healthcare worker (HCW) absenteeism. The bacillus Calmette-Guérin (BCG) vaccine may provide non-specific protection against respiratory infections through enhancement of trained immunity. We investigated the impact of BCG vaccination on HCW absenteeism during the COVID-19 pandemic.

Induction of trained immunity by influenza vaccination - impact on COVID-19.

Non-specific protective effects of certain vaccines have been reported, and long-term boosting of innate immunity, termed trained immunity, has been proposed as one of the mechanisms mediating these effects. Several epidemiological studies suggested cross-protection between influenza vaccination and COVID-19. In a large academic Dutch hospital, we found that SARS-CoV-2 infection was less common among employees who had received a previous influenza vaccination: relative risk reductions of 37% and 49% were observed following influenza vaccination during the first and second COVID-19 waves, respectively.

induction of trained immunity in adherent human monocytes.

A growing number of studies show that innate immune cells can undergo functional reprogramming, facilitating a faster and enhanced response to heterologous secondary stimuli. This concept has been termed "trained immunity." We outline here a protocol to recapitulate this using adherent monocytes from consecutive isolation of peripheral blood mononuclear cells.