Recombinant BCG Expressing the Subunit 1 of Pertussis Toxin Induces Innate Immune Memory and Confers Protection against Non-Related Pathogens

Kanno, Alex I.; Boraschi, Diana; Leite, Luciana C. C.; Rodríguez, Dunia

doi:10.3390/vaccines10020234

Cited by 8 publications

(5 citation statements)

References 43 publications

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“…Very recently, rBCG::PTA was also found to be a stronger inducer of innate immune memory than pBCG [ 94 ]. Mouse bone-marrow-derived macrophages and peritoneal macrophages stimulated with rBCG::PTA produced more inflammatory cytokines, such as TNF-α and IL-6, upon heterologous challenge with Candida albicans , Staphylococcus aureus or lipopolysaccharide than pBCG-stimulated cells.…”

Section: Recombinant Bcg Strains Producing Bacterial Effectorsmentioning

confidence: 99%

Recombinant BCG to Enhance Its Immunomodulatory Activities

Kowalewicz-Kulbat

Locht

2022

Vaccines

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The bacillus Calmette–Guérin (BCG) is an attenuated Mycobacterium bovis derivative that has been widely used as a live vaccine against tuberculosis for a century. In addition to its use as a tuberculosis vaccine, BCG has also been found to have utility in the prevention or treatment of unrelated diseases, including cancer. However, the protective and therapeutic efficacy of BCG against tuberculosis and other diseases is not perfect. For three decades, it has been possible to genetically modify BCG in an attempt to improve its efficacy. Various immune-modulatory molecules have been produced in recombinant BCG strains and tested for protection against tuberculosis or treatment of several cancers or inflammatory diseases. These molecules include cytokines, bacterial toxins or toxin fragments, as well as other protein and non-protein immune-modulatory molecules. The deletion of genes responsible for the immune-suppressive properties of BCG has also been explored for their effect on BCG-induced innate and adaptive immune responses. Most studies limited their investigations to the description of T cell immune responses that were modified by the genetic modifications of BCG. Some studies also reported improved protection by recombinant BCG against tuberculosis or enhanced therapeutic efficacy against various cancer forms or allergies. However, so far, these investigations have been limited to mouse models, and the prophylactic or therapeutic potential of recombinant BCG strains has not yet been illustrated in other species, including humans, with the exception of a genetically modified BCG strain that is now in late-stage clinical development as a vaccine against tuberculosis. In this review, we provide an overview of the different molecular engineering strategies adopted over the last three decades in order to enhance the immune-modulatory potential of BCG.

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Section: Recombinant Bcg Strains Producing Bacterial Effectorsmentioning

confidence: 99%

Recombinant BCG to Enhance Its Immunomodulatory Activities

Kowalewicz-Kulbat

Locht

2022

Vaccines

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“…Intriguingly, Toll-like receptors or NOD-like receptors agonists were effective against Toxoplasma and E. coli, respectively [42][43][44]. Likewise, compelling evidence of BCG vaccines unveiled a profound effect on preventing infection without involving adaptive immune cells [15,45]. The nonspecific innate memory induced by BCG was mediated by type II interferon.…”

Section: Characteristics Of Adaptive and Trained Immunitymentioning

confidence: 99%

Trained Immunity as a Prospective Tool against Emerging Respiratory Pathogens

Joseph

2022

Vaccines

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Although parental vaccines offer long-term protection against homologous strains, they rely exclusively on adaptive immune memory to produce neutralizing antibodies that are ineffective against emerging viral variants. Growing evidence highlights the multifaceted functions of trained immunity to elicit a rapid and enhanced innate response against unrelated stimuli or pathogens to subsequent triggers. This review discusses the protective role of trained immunity against respiratory pathogens and the experimental models essential for evaluating novel inducers of trained immunity. The review further elaborates on the potential of trained immunity to leverage protection against pathogens via the molecular patterns of antigens by pathogen recognition receptors (PPRs) on innate immune cells. The review also focuses on integrating trained innate memory with adaptive memory to shape next-generation vaccines by coupling each one’s unique characteristics.

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“…Intriguingly, Toll-like receptors or NOD-like receptors agonists were effective against toxoplasma and E.coli, respectively [33][34][35][36]. Likewise, compelling evidence of BCG vaccines unveiled a profound effect on preventing heterogenous infection without involving adaptive immune cells [14] [37]. The nonspecific innate memory induced by BCG was mediated by type II interferon.…”

Section: Characteristics Of Adaptive and Trained Immunitymentioning

confidence: 99%

Trained Immunity as a Prospective Tool against Emerging Respiratory Pathogens

Joseph¹

2022

Preprint

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The COVID-19 pandemic exposed the vulnerability of current vaccine technologies characterized by a slow onset of action and antigen-specific immune response. Although parental vaccines offer long-term protection against homologous strains, they rely exclusively on adaptive immune memory to produce neutralizing antibodies that are ineffective against new vaccine variants. Moreover, growing evidence highlights the multifaceted functions of trained immunity to elicit a rapid and enhanced innate response against unrelated stimuli or pathogens to subsequent triggers. This review discusses the protective role of trained immunity against respiratory pathogens and the experimental models essential for evaluating novel inducers of trained immunity. We further elaborate on the potential of trained immunity to leverage protection against emerging pathogens via recognition of diverse antigens by pathogen recognition receptors (PPRs) on innate immune cells. We also propose integrating trained- with adaptive- immunity to shape next-generation vaccines by coupling each one's unique characteristics.

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Recombinant BCG Expressing the Subunit 1 of Pertussis Toxin Induces Innate Immune Memory and Confers Protection against Non-Related Pathogens

Cited by 8 publications

References 43 publications

Recombinant BCG to Enhance Its Immunomodulatory Activities

Recombinant BCG to Enhance Its Immunomodulatory Activities

Trained Immunity as a Prospective Tool against Emerging Respiratory Pathogens

Trained Immunity as a Prospective Tool against Emerging Respiratory Pathogens

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