Lessons from Bacillus Calmette-Guérin: Harnessing Trained Immunity for Vaccine Development

Pasco, Samuel T; Anguíta, Juan

doi:10.3390/cells9092109

Cited by 18 publications

(12 citation statements)

References 83 publications

(110 reference statements)

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“…24 Importantly, molecular mechanisms underlying these long-term responses have been, at least partly, elucidated in the last two decades, 9,[25][26][27] increasing the possibility of improving, for example, vaccination strategies. 28,29 However, these studies have been only focused on analyzing the response of innate immune cells to pathogenic microbes, such as Candida albicans or Mycobacterium tuberculosis, almost exclusively using microbe-derived PAMPs or dead microbial cells. 11 Unfortunately, no attention has been paid to the role of this phenomenon in the interaction of the host with the myriads of beneficial microbial species inhabiting the human body, even though a huge plasticity of innate immune memory in response to diverse stimuli has been previously reported.…”

Section: Discussionmentioning

confidence: 99%

The commensal bacterium Lactiplantibacillus plantarum imprints innate memory-like responses in mononuclear phagocytes

et al. 2021

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Gut microbiota is a constant source of antigens and stimuli to which the resident immune system has developed tolerance. However, the mechanisms by which mononuclear phagocytes, specifically monocytes/macrophages, cope with these usually pro-inflammatory signals are poorly understood. Here, we show that innate immune memory promotes anti-inflammatory homeostasis, using as model strains of the commensal bacterium Lactiplantibacillus plantarum. Priming of monocytes/ macrophages with bacteria, especially in its live form, enhances bacterial intracellular survival and decreases the release of pro-inflammatory signals to the environment, with lower production of TNF and higher levels of IL-10. Analysis of the transcriptomic landscape of these cells shows downregulation of pathways associated with the production of reactive oxygen species (ROS) and the release of cytokines, chemokines and antimicrobial peptides. Indeed, the induction of ROS prevents memory-induced bacterial survival. In addition, there is a dysregulation in gene expression of several metabolic pathways leading to decreased glycolytic and respiratory rates in memory cells. These data support commensal microbe-specific metabolic changes in innate immune memory cells that might contribute to homeostasis in the gut.

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Section: Discussionmentioning

confidence: 99%

The commensal bacterium Lactiplantibacillus plantarum imprints innate memory-like responses in mononuclear phagocytes

et al. 2021

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“…A number of lines of evidence have indicated that childhood vaccination with some live-attenuated vaccines, such as the tuberculosis vaccine, bacilli Calmette-Guerin (BCG), smallpox and polio vaccines, can induce beneficial, nonspecific, heterologous vaccine effects against unrelated pathogens by eliciting innate cell-mediated immune responses (Nascimento et al, 2020;Pasco and Anguita, 2020). These innate cell-based heterologous effects are referred to as trained immunity.…”

Section: Heterologous Vaccine Effects Of Licensed Bacterial and Viral...mentioning

confidence: 99%

COVID-19 vaccine development based on recombinant viral and bacterial vector systems: combinatorial effect of adaptive and trained immunity

Lee

Kim

2022

J Microbiol.

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Severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) infection, which causes coronavirus disease 2019 (COVID-19), has led to many cases and deaths worldwide. Therefore, a number of vaccine candidates have been developed to control the COVID-19 pandemic. Of these, to date, 21 vaccines have received emergency approval for human use in at least one country. However, the recent global emergence of SARS-CoV-2 variants has compromised the efficacy of the currently available vaccines. To protect against these variants, the use of vaccines that modulate T cell-mediated immune responses or innate immune cell memory function, termed trained immunity, is needed. The major advantage of a vaccine that uses bacteria or viral systems for the delivery of COVID-19 antigens is the ability to induce both T cell-mediated and humoral immune responses. In addition, such vaccine systems can also exert off-target effects via the vector itself, mediated partly through trained immunity; compared to other vaccine platforms, suggesting that this approach can provide better protection against even vaccine escape variants. This review presents the current status of the development of COVID-19 vaccines based on recombinant viral and bacterial delivery systems. We also discuss the current status of the use of licensed live vaccines for other infections, including BCG, oral polio and MMR vaccines, to prevent COVID-19 infections.

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“…Altogether, harnessing the TIbV concept has been suggested as a crucial step in future vaccine development and implementation, because a wide range of clinical applications may benefit to some extent from their use [150].…”

Section: The Potential Clinical Applications Of Tibvs In the Context ...mentioning

confidence: 99%

Trained Immunity-Based Vaccines: A Ready-to-Act Strategy to Tackle Viral Outbreaks

Conejero¹,

Saz-Leal²,

Subiza³

2022

Current Perspectives on Viral Disease Outbreaks - Epidemiology, Detection and Control

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Viral outbreaks have become significant threats to global human public health. New emerging viruses, pathogen mutations, and even the progressive loss of efficacy in some existing vaccines are behind this problem, which is amplified by the rapid virus spread given the ease of current mobility. Taking into account that these outbreaks arise in the absence of conventional effective vaccines, alternative approaches based on trained (innate) immunity are being considered. This immunity is dependent on a functional reprogramming of innate immune cells, leading to an enhanced nonspecific response towards different pathogens, including viruses. Trained immunity-based vaccines (TIbVs), defined as vaccine formulations containing trained immunity inducers, could be used during viral outbreaks to confer non-specific protection but also to enhance adaptive specific immune responses. In this chapter, we aim to illustrate how TIbVs could tackle the above-mentioned situations derived from viral outbreaks, reviewing the potential of available TIbVs in such urgent situations with a special mention to COVID-19.

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Lessons from Bacillus Calmette-Guérin: Harnessing Trained Immunity for Vaccine Development

Cited by 18 publications

References 83 publications

The commensal bacterium Lactiplantibacillus plantarum imprints innate memory-like responses in mononuclear phagocytes

The commensal bacterium Lactiplantibacillus plantarum imprints innate memory-like responses in mononuclear phagocytes

COVID-19 vaccine development based on recombinant viral and bacterial vector systems: combinatorial effect of adaptive and trained immunity

Trained Immunity-Based Vaccines: A Ready-to-Act Strategy to Tackle Viral Outbreaks

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