Does BCG revaccination protect against the development of asthma?

Andrade, Cláudia Ribeiro de; Cunha, Sérgio Souza da; Alvim, Cristina Gonçalves; Fontes, Maria Jussara Fernandes; Bedran, Renata Marcos; Binato, Henrique A.; Camargos, Paulo Augusto Moreira

doi:10.1016/j.rmed.2012.10.009

Cited by 6 publications

(3 citation statements)

References 7 publications

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“…4a). These findings of certain anti-inflammatory consequences of BCG-WT may correlate with the observation that in countries that routinely use BCG for TB prevention, vaccinees display reduced levels of asthma and atopic dermatitis 55,56 . In contrast, this expansion of M-MDSCs in macrophages by BCG-WT was reversed by cyclic-di-AMP overexpression, which is in keeping with a recent study showing that STING pathway activation reduces the induction of MDSCs in certain cancers 57 .…”

Section: Discussionsupporting

confidence: 53%

Re-engineered BCG overexpressing cyclic di-AMP augments trained immunity and exhibits improved efficacy against bladder cancer

et al. 2022

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In addition to its role as a TB vaccine, BCG has been shown to elicit heterologous protection against many other pathogens including viruses through a process termed trained immunity. Despite its potential as a broadly protective vaccine, little has been done to determine if BCG-mediated trained immunity levels can be optimized. Here we re-engineer BCG to express high levels of c-di-AMP, a PAMP recognized by stimulator of interferon genes (STING). We find that BCG overexpressing c-di-AMP elicits more potent signatures of trained immunity including higher pro-inflammatory cytokine responses, greater myeloid cell reprogramming toward inflammatory and activated states, and enhances epigenetic and metabolomic changes. In a model of bladder cancer, we also show that re-engineered BCG induces trained immunity and improved functionality. These results indicate that trained immunity levels and antitumor efficacy may be increased by modifying BCG to express higher levels of key PAMP molecules.

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Section: Discussionsupporting

confidence: 53%

Re-engineered BCG overexpressing cyclic di-AMP augments trained immunity and exhibits improved efficacy against bladder cancer

et al. 2022

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“…These findings suggest that classical (WT) BCG may promote some degree of immunosuppression in the TME that may partly offset the benefits of a pro-inflammatory M1 repolarization. This BCG-mediated expansion of M-MDSCs may contribute to BCG unresponsiveness in certain NMIBC patients, and it may explain the observation that in countries which routinely use BCG for TB prevention, vaccinees display reduced levels of asthma and atopic dermatitis 74,75 . In contrast, expansion of M-MDSCs in macrophages by classical (WT) BCG was reversed by STING agonist overexpression which is in keeping with a recently unveiled function of the STING-SOCS1-STAT3 pathway in promoting antitumor immunity by down-regulating the induction of MDSCs in nasopharyngeal carcinoma 76 .…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Recombinant BCG overexpressing a STING agonist elicits trained immunity and improved antitumor efficacy in non-muscle invasive bladder cancer

Singh

Praharaj

Lombardo

et al. 2020

Preprint

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BCG remains first-line therapy for non-muscle invasive bladder cancer (NIMBC) but its mechanism of action is not fully understood. We developed a recombinant BCG (rBCG) that releases the STING agonist, c-di-AMP. Compared with BCG, rBCG demonstrated superior antitumor efficacy in models of NMIBC, more potent pro-inflammatory cytokine responses, greater myeloid cell reprogramming (M1 shift) and enhanced epigenetic and metabolomic changes favoring antitumor immunity. These findings are signatures of trained immunity and reveal that STING pathway activation is a proximal trigger in trained immunity remodeling. Trained immunity may be a central mechanism for both BCG and rBCG antitumor activity in NMIBC. INTRODUCTION:Bacillus Calmette-Guérin (BCG)--the only FDA-approved bacterial agent for cancer immunotherapy--has been in use for the treatment of high-risk non-muscle invasive bladder cancer (NMIBC) as a first-line therapy since the late 1970s. More than one-third of patient's with NMIBC will experience tumor recurrence after receiving BCG, and these patients have limited options other than removal of the bladder and creation of a urinary diversion -a major life-altering event. Thus, there is a significant unmet need for improved versions of BCG that provide superior response rates and prevent disease progression 1 . At the current time intravesical options for bladder preserving therapy remain limited.Following bladder instillation, BCG induces a local inflammatory response accompanied by infiltration of granulocytes, macrophages, natural killer (NK) cells, dendritic cells (DCs), and CD4 + and CD8 + T cells, accompanied by release of pro-inflammatory cytokines including IL-6, TNF-a, and IFN-g 2-7 . However, the specific immune mechanisms leading to BCG-mediated tumor eradication as well as BCG-resistance are not well-understood. BCG has been found to impart potent heterologous protection against non-related viral and bacterial infections; it elicits this protection via an innate immune memory mechanism known as trained immunity 8-11 . Trained immunity is characterized by metabolic, epigenetic and transcriptional reprogramming of both myeloid and lymphoid lineages 12-15 but it has not been extensively studied as an antitumor mechanism during BCG immunotherapy for NMIBC.Recent studies have implicated the DNA-sensing receptor cyclic GMP-AMP synthase (cGAS) and its downstream signaling effector, stimulator of interferon genes (STING), in a key immune response pathway known as the cytosolic surveillance pathway (CSP), which responds to DNA and cyclic dinucleotides aberrantly present in the cytosol [16][17][18][19] . Activated cGAS catalyzes the formation of 2′3′-cGAMP, a cyclic dinucleotide (CDN) that is a potent STING agonist.Activation of STING leads to stimulation of Type I interferon and NF-κB-mediated immune responses, including elevated dendritic cell priming and T-effector (Teff) cell recruitment 20-23 . 4Small molecule STING agonists elicit potent pro-inflammatory responses, and correspondingly have shown signific...

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“…В свою очередь, исследователи не обнаружили связи между заболеваемостью бронхиальной астмой, ассоциированной и не ассоциированной с аллергическим ринитом и атопическим дерматитом, и ревакцинацией BCG среди 2213 детей в возрасте 12-13 лет [37].…”

Section: частота развития аллергопатологии у детей вакцинированных против туберкулезаunclassified

Prevalence of Allergic Diseases in Children Vaccinated Against Tuberculosis and Hepatitis B in the Early Neonatal Period: Literature Review

2021

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Background. T-cell response is shifted towards Th2-type predominance in newborns. This makes them particularly vulnerable to exposure of various external pathogens, development of severe infections, moreover, it is also a risk factor for allergic diseases development. Various methods of switching the immune response to Th1-type are currently under research, and one of them is vaccination.Objective. The aim of the study is to provide data on the prevalence of allergic pathology among children vaccinated against tuberculosis and hepatitis B, as well as the effect of vaccines on immune response type.Results. Data on both increase and decrease in the prevalence of atopic conditions in children vaccinated with BCG and against hepatitis B were analyzed, thus, most of them cannot be considered reliable. The results of several large studies do not reveal any correlation between vaccination and the presence of allergic disease in children. There is data that BCG and hepatitis B vaccines shift the immune response towards Th1-type activation.Conclusion. Vaccination in the early neonatal period may affect switching of the immune response towards Th1-type. That, in turn, can affect the prevalence of allergic pathology in vaccinated children. However, the data available for now is not sufficient to reliably estimate the possible effect of vaccination on atopic conditions manifestation in the future.

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Does BCG revaccination protect against the development of asthma?

Cited by 6 publications

References 7 publications

Re-engineered BCG overexpressing cyclic di-AMP augments trained immunity and exhibits improved efficacy against bladder cancer

Re-engineered BCG overexpressing cyclic di-AMP augments trained immunity and exhibits improved efficacy against bladder cancer

WITHDRAWN: Recombinant BCG overexpressing a STING agonist elicits trained immunity and improved antitumor efficacy in non-muscle invasive bladder cancer

Prevalence of Allergic Diseases in Children Vaccinated Against Tuberculosis and Hepatitis B in the Early Neonatal Period: Literature Review

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