Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice

Stevens, Natalie E.; Wolfswinkel, Marjolein van; Bao, Winnie; Ryan, Feargal J.; Brook, Byron; Amenyogbe, Nelly; Marshall, Helen; Lynn, Miriam A.; Kollmann, Tobias R.; Tumes, Damon J.; Lynn, David J.

doi:10.1016/j.vaccine.2021.03.084

Cited by 7 publications

(5 citation statements)

References 61 publications

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“…Similarly, in their ATAC seq data, Steven et al. ( 38 ) found that BCG immunization increased the accessibility of genes related to specific immune and metabolic pathways.…”

Section: Introductionmentioning

confidence: 84%

“…Stevens et al. ( 38 ) observed genes involved in IFN-α, IFN-γ responses, and IL6/JAK/STAT3 signaling were statistically enriched among genes with altered chromatin accessibility when evaluating epigenetic changes in cDCs from either BCG or DTPw-immunized mice. In γδ T cells from BCG-immunized calves, annotation of the genes proximal to the DAPs in the open chromatin showed up to a 4-log2 FC increase in genes related to immune functions compared to γδ T cells from control calves, including genes related to inflammatory responses and IFN-α responses ( Supplementary Material 4 ).…”

Section: Discussionmentioning

confidence: 99%

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Evidence of innate training in bovine γδ T cells following subcutaneous BCG administration

Samuel,

Diaz,

Maina

et al. 2024

Front. Immunol.

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The Bacillus Calmette Guerin (BCG) vaccine has been shown to induce non-specific protection against diseases other than tuberculosis in vaccinated individuals, attributed to the induction of trained immunity. We have previously demonstrated that BCG administration induces innate immune training in mixed peripheral blood mononuclear cells and monocytes in calves. Gamma Delta (γδ) T cells are non-conventional T cells that exhibit innate and adaptive immune system features. They are in higher proportion in the peripheral blood of cattle than humans or rodents and play an essential role in bovine immune response to pathogens. In the current study, we determined if BCG administration induced innate immune training in bovine γδ T cells. A group of 16 pre-weaned Holstein calves (2-4 d age) were enrolled in the study and randomly assigned to vaccine and control groups (n=8/group). The vaccine group received two doses of 106 colony forming units (CFU) BCG Danish strain subcutaneously, separated by 2 weeks. The control group remained unvaccinated. Gamma delta T cells were purified from peripheral blood using magnetic cell sorting three weeks after receiving the 1st BCG dose. We observed functional changes in the γδ T cells from BCG-treated calves shown by increased IL-6 and TNF-α cytokine production in response to in vitro stimulation with Escherichia coli LPS and PAM3CSK4. ATAC-Seq analysis of 78,278 regions of open chromatin (peaks) revealed that γδ T cells from BCG-treated calves had an altered epigenetic status compared to cells from the control calves. Differentially accessible peaks (DAP) found near the promoters of innate immunity-related genes like Siglec14, Irf4, Ifna2, Lrrfip1, and Tnfrsf10d were 1 to 4-fold more accessible in cells from BCG-treated calves. MOTIF enrichment analysis of the sequences within DAPs, which explores transcription factor binding motifs (TFBM) upstream of regulatory elements, revealed TFBM for Eomes and IRF-5 were among the most enriched transcription factors. GO enrichment analysis of genes proximal to the DAPs showed enrichment of pathways such as regulation of IL-2 production, T-cell receptor signaling pathway, and other immune regulatory pathways. In conclusion, our study shows that subcutaneous BCG administration in pre-weaned calves can induce innate immune memory in the form of trained immunity in γδ T cells. This memory is associated with increased chromatin accessibility of innate immune response-related genes, thereby inducing a functional trained immune response evidenced by increased IL-6 and TNF-α cytokine production.

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“…Similarly, in their ATAC seq data, Steven et al. ( 38 ) found that BCG immunization increased the accessibility of genes related to specific immune and metabolic pathways.…”

Section: Introductionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Evidence of innate training in bovine γδ T cells following subcutaneous BCG administration

Samuel,

Diaz,

Maina

et al. 2024

Front. Immunol.

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“…Training of Monocytes/Macrophages in Blood Ex Vivo: In vitro training of primary monocytes/macrophages in blood was performed according to the method mentioned before. [42] 100 μL of EDTA-anticoagulated blood was washed with PBS and centrifuged at 300 g for 5 min. The cell pellets were lysed with 1000 μL red blood cell lysis buffer at room temperature for 2 min to obtain single cells.…”

Section: Methodsmentioning

confidence: 99%

Engineered Probiotic‐Based Personalized Cancer Vaccine Potentiates Antitumor Immunity through Initiating Trained Immunity

Chen,

Yong,

Wei

et al. 2023

Advanced Science

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Cancer vaccines hold great potential for clinical cancer treatment by eliciting T cell‐mediated immunity. However, the limited numbers of antigen‐presenting cells (APCs) at the injection sites, the insufficient tumor antigen phagocytosis by APCs, and the presence of a strong tumor immunosuppressive microenvironment severely compromise the efficacy of cancer vaccines. Trained innate immunity may promote tumor antigen‐specific adaptive immunity. Here, a personalized cancer vaccine is developed by engineering the inactivated probiotic Escherichia coli Nissle 1917 to load tumor antigens and β‐glucan, a trained immunity inducer. After subcutaneous injection, the cancer vaccine delivering model antigen OVA (BG/OVA@EcN) is highly accumulated and phagocytosed by macrophages at the injection sites to induce trained immunity. The trained macrophages may recruit dendritic cells (DCs) to facilitate BG/OVA@EcN phagocytosis and the subsequent DC maturation and T cell activation. In addition, BG/OVA@EcN remarkably enhances the circulating trained monocytes/macrophages, promoting differentiation into M1‐like macrophages in tumor tissues. BG/OVA@EcN generates strong prophylactic and therapeutic efficacy to inhibit tumor growth by inducing potent adaptive antitumor immunity and long‐term immune memory. Importantly, the cancer vaccine delivering autologous tumor antigens efficiently prevents postoperative tumor recurrence. This platform offers a facile translatable strategy to efficiently integrate trained immunity and adaptive immunity for personalized cancer immunotherapy.

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“…Accessibility of transcription factors to their cognate gene targets results in a more rapid and potent response to future stimulation to the same signals, essentially the innate immune response version of T cell and B cell memory. Importantly, trained immunity has been demonstrated to enhance immune responses in the context of vaccination, initially with Bacillus Calmette-Guérin (BCG) [66][67][68] and the diphtheria, tetanus and pertussis (DTP) vaccines 66 and more recently with the influenza vaccines 55 . Studies have been performed to identify pre-vaccination signatures that predict vaccine efficacy and outcome [69][70][71][72] .…”

Section: Memory: It Is Not Just For T Cells and B Cells Anymorementioning

confidence: 99%

Fighting the SARS-CoV-2 pandemic requires a global approach to understanding the heterogeneity of vaccine responses

et al. 2022

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ver the past two decades, the world has experienced a substantial number of disease outbreaks from viral infections including yellow fever, dengue fever, Ebola, Zika, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome and the ongoing novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic 1 . The SARS-CoV-2 pandemic has illuminated how disruptive sustained infectious disease outbreaks can be on society. Given the unpredictability of when the next pandemic will emerge, strengthening our ability to respond rapidly to any infectious disease threat is a global priority.In what may be one of the most impressive accomplishments of modern medicine, multiple effective vaccines were developed against SARS-CoV-2 in less than 12 months after the initial outbreak. As of February 2022 ten coronavirus disease 2019 (COVID-19) vaccines are currently approved for full or emergency use authorization by the World Health Organization (https://covid19.trackvaccines.org/agency/who/). These approved vaccines span four distinct vaccine platforms, providing an additional layer of diversity in potential vaccine responses. The Moderna and Pfizer-BioNTech vaccines both use modified mRNAs to produce antigen upon vaccination 2,3 . Both vaccines use lipid nanoparticle-encapsulated formulations to deliver mRNA that encodes for a prefusion stabilized, full-length SARS-CoV-2 spike (S) protein. The Johnson & Johnson (Ad26 vector) and AstraZeneca AZD1222 (ChAdOx1 vector) vaccines use distinct replication-incompetent adenoviral vectors to deliver antigen (the prefusion stabilized, full-length S protein) 4,5 . The Sinopharm and Sinovac-CoronaVac platforms utilize β-propiolactone-inactivated virus produced in Vero E6 cells and are formulated with the adjuvant alum to promote immunogenicity 6,7 . Protein subunit-based platforms are in advanced stages of development, with one approved for emergency use authorization in Indonesia (Novavax 8 ; clinical trial no. NCT04742738). Approved vaccines have efficacy rates of ~50-95%, with Moderna and Pfizer exhibiting the highest rates of short-term efficacy.

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Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice

Cited by 7 publications

References 61 publications

Evidence of innate training in bovine γδ T cells following subcutaneous BCG administration

Evidence of innate training in bovine γδ T cells following subcutaneous BCG administration

Engineered Probiotic‐Based Personalized Cancer Vaccine Potentiates Antitumor Immunity through Initiating Trained Immunity

Fighting the SARS-CoV-2 pandemic requires a global approach to understanding the heterogeneity of vaccine responses

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