Trained immunity: A Yin‐Yang balance

Hu, Zhidong; Lu, Shuihua; Lowrie, Douglas B.; Fan, Xiao‐Yong

doi:10.1002/mco2.121

Cited by 14 publications

(7 citation statements)

References 150 publications

(323 reference statements)

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“…However, trained immunity can also be detrimental in some disease settings. In principle, excessive or chronic activation of innate immune responses by inducing trained immunity could lead to excessive inflammation or immunosuppression during chronic disease [63]. A growing body of research provides evidence that the reprogramming of trained immunity may play a role in the maintenance of a variety of diseases.…”

Section: Discussionmentioning

confidence: 99%

A "trained immunity" inducer-adjuvanted nanovaccine reverses the growth of established tumors in mice

Li²,

Zheng³

et al. 2023

J Nanobiotechnol

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Innate immune cells are critical in antitumor immune surveillance and the development of antitumor adaptive cellular immunity. Trained innate immune cells demonstrate immune memory-like characteristics, producing more vigorous immune responses to secondary homologous or heterologous stimuli. This study aimed to investigate whether inducing trained immunity is beneficial when using a tumor vaccine to promote antitumor adaptive immune responses. A biphasic delivery system was developed with the trained immunity inducer Muramyl Dipeptide (MDP) and specific tumor antigen human papillomavirus (HPV) E7 peptide encapsulated by poly(lactide-co-glycolide)-acid(PLGA) nanoparticles (NPs), and the NPs along with another trained immunity agonist, β-glucan, were further embedded in a sodium alginate hydrogel. The nanovaccine formulation demonstrated a depot effect for E7 at the injection site and targeted delivery to the lymph nodes and dendritic cells (DCs). The antigen uptake and maturation of DCs were significantly promoted. A trained immunity phenotype, characterized by increased production of IL-1β, IL-6, and TNF-α, was induced in vitro and in vivo in response to secondary homologous or heterologous stimulation. Furthermore, prior innate immune training enhanced the antigen-specific INF-γ-expressing immune cell response elicited by subsequent stimulation with the nanovaccine. Immunization with the nanovaccine completely inhibited the growth of TC-1 tumors and even abolished established tumors in mice. Mechanistically, the inclusion of β-glucan and MDP significantly enhanced the responses of tumor-specific effector adaptive immune cells. The results strongly suggest that the controlled release and targeted delivery of an antigen and trained immunity inducers with an NP/hydrogel biphasic system can elicit robust adaptive immunity, which provides a promising tumor vaccination strategy. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

A "trained immunity" inducer-adjuvanted nanovaccine reverses the growth of established tumors in mice

Li²,

Zheng³

et al. 2023

J Nanobiotechnol

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“…However, recently it has been shown that innate immunity also plays an important role in immune memory against homologous or even heterologous challenges ( 145 , 146 ). Trained immunity, a de facto innate immune memory, has been defined as a long-term functional reprogramming of the innate immune cells that is evoked by endogenous or exogenous insults, with the cells then returning to a non-activated state and showing altered inflammatory responses against a second challenge ( 147 , 148 ).…”

Section: Latest Findings That Facilitate Tb Vaccine Research Developmentmentioning

confidence: 99%

Research Advances for Virus-vectored Tuberculosis Vaccines and Latest Findings on Tuberculosis Vaccine Development

Lowrie

et al. 2022

Front. Immunol.

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Tuberculosis (TB), caused by respiratory infection with Mycobacterium tuberculosis, remains a major global health threat. The only licensed TB vaccine, the one-hundred-year-old Bacille Calmette-Guérin has variable efficacy and often provides poor protection against adult pulmonary TB, the transmissible form of the disease. Thus, the lack of an optimal TB vaccine is one of the key barriers to TB control. Recently, the development of highly efficacious COVID-19 vaccines within one year accelerated the vaccine development process in human use, with the notable example of mRNA vaccines and adenovirus-vectored vaccines, and increased the public acceptance of the concept of the controlled human challenge model. In the TB vaccine field, recent progress also facilitated the deployment of an effective TB vaccine. In this review, we provide an update on the current virus-vectored TB vaccine pipeline and summarize the latest findings that might facilitate TB vaccine development. In detail, on the one hand, we provide a systematic literature review of the virus-vectored TB vaccines are in clinical trials, and other promising candidate vaccines at an earlier stage of development are being evaluated in preclinical animal models. These research sharply increase the likelihood of finding a more effective TB vaccine in the near future. On the other hand, we provide an update on the latest tools and concept that facilitating TB vaccine research development. We propose that a pre-requisite for successful development may be a better understanding of both the lung-resident memory T cell-mediated mucosal immunity and the trained immunity of phagocytic cells. Such knowledge could reveal novel targets and result in the innovative vaccine designs that may be needed for a quantum leap forward in vaccine efficacy. We also summarized the research on controlled human infection and ultra-low-dose aerosol infection murine models, which may provide more realistic assessments of vaccine utility at earlier stages. In addition, we believe that the success in the ongoing efforts to identify correlates of protection would be a game-changer for streamlining the triage of multiple next-generation TB vaccine candidates. Thus, with more advanced knowledge of TB vaccine research, we remain hopeful that a more effective TB vaccine will eventually be developed in the near future.

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“…Bacterial and fungal cells and their components (LPS, β-glucan and chitin), virus and parasites are the best-known exogenous ones, but there are other endogenous ones like oxidized low-density lipoprotein, apolipoprotein(a), aldosterone or adrenaline [34]. Since training or tolerizing effects are observed, it must be underscored that TRAIM is a complex delicately balanced mechanism that is only beginning to be understood, and that the same compound, depending on time and concentration might cause opposite effects [53,55].…”

Section: Traim Inductorsmentioning

confidence: 99%

“…Bacterial and fungal cells and their components (LPS, β‐glucan and chitin), virus and parasites are the best‐known exogenous ones, but there are other endogenous ones like oxidized low‐density lipoprotein, apolipoprotein(a), aldosterone or adrenaline [34]. Since training or tolerizing effects are observed, it must be underscored that TRAIM is a complex delicately balanced mechanism that is only beginning to be understood, and that the same compound, depending on time and concentration might cause opposite effects [53, 55]. In this review, we will focus on two examples: on one side, a whole bacterial cell, Mycobacterium bovis inactivated vaccine which would be the closest approach to a natural challenge without its risks, and on the other, one structural component of those types of organism found in bacterial cell wall a broadly known as glycan, an encompassing term grouping large glycosidically bound saccharide polymers including those linked to lipids or proteins, that probably represents the type of true molecular effector of TRAIM present in the former in more complex forms.…”

Section: Traim Inductorsmentioning

confidence: 99%

Heat inactivated mycobacteria, alpha‐Gal and zebrafish: Insights gained from experiences with two promising trained immunity inductors and a validated animal model

et al. 2022

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Trained immunity (TRAIM) may be defined as a form of memory where innate immune cells such as monocytes, macrophages, dendritic and natural killer (NK) cells undergo an epigenetic reprogramming that enhances their primary defensive capabilities. Cross-pathogen protective TRAIM can be triggered in different hosts by exposure to live microbes or microbe-derived products such as heat-inactivated Mycobacterium bovis or with the glycan α-Gal to elicit protective responses against several pathogens. We review the TRAIM paradigm using two models representing distinct scales of immune sensitization: the whole bacterial cell and one of its building blocks, the polysaccharides or glycans. Observations point out to macrophage lytic capabilities and cytokine regulation as two key components in non-specific innate immune responses against infections. The study of the TRAIM response deserves attention to better characterize the

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Trained immunity: A Yin‐Yang balance

Cited by 14 publications

References 150 publications

A "trained immunity" inducer-adjuvanted nanovaccine reverses the growth of established tumors in mice

A "trained immunity" inducer-adjuvanted nanovaccine reverses the growth of established tumors in mice

Research Advances for Virus-vectored Tuberculosis Vaccines and Latest Findings on Tuberculosis Vaccine Development

Heat inactivated mycobacteria, alpha‐Gal and zebrafish: Insights gained from experiences with two promising trained immunity inductors and a validated animal model

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