scholarly journals Hypothetical Immunological and Immunogenetic Model of Heterogenous Effects of BCG Vaccination in SARS-CoV-2 Infections: BCG-induced Trained and Heterologous Immunity

2021 ◽  
pp. e551
Author(s):  
Dženan Kovačić ◽  
Andrej A. Gajić ◽  
Dado Latinović ◽  
Adna Softić
Keyword(s):  
Cross Reactivity ◽  
Innate Immune ◽  
Cytokine Secretion ◽  
Bcg Vaccine ◽  
Immune Memory ◽  
Host Immune System ◽  
Bcg Vaccination ◽  
Heterologous Immunity ◽  
Specific Effects ◽  
Secretion Profile

Though SARS-CoV-2 infections are yet to be completely characterised in a host-pathogen interaction context, some of the mechanisms governing the interaction between the novel betacoronavirus and the human host, have been brought to light in satisfactory detail. Among the emerging evidence, postulates regarding potential benefits of innate immune memory and heterologous immunity have been put under discussion. Innate immune memory entails epigenetic reprogramming of innate immune cells caused by vaccination or infections, whereas heterologous immunity denotes cross-reactivity of T cells with unrelated epitopes and bystander CD8+ activation. Familiarization of the host immune system with a certain pathogen, educates monocytes, macrophages and other innate cells into phenotypes competent for combating unrelated pathogens. Indeed, the resolution at which non-specific innate immune memory occurs, is predominant at the level of enhanced cytokine secretion as a result of epigenetic alterations. One vaccine whose non-specific effects have been documented and harnessed in treating infections, cancer and autoimmunity, is the Bacillus Calmette–Guérin (BCG) vaccine currently used for immunization against pulmonary tuberculosis (TB). The BCG vaccine induces a diverse cytokine secretion profile in immunized subjects, which in turn may stimulate epigenetic changes mediated by immunoreceptor signalling. Herein, we provide a concise summarization of previous findings regarding the effects of the BCG vaccine on innate immune memory and heterologous immunity, supplemented with clinical evidence of the non-specific effects of this vaccine on non-mycobacterial infections, cancer and autoimmunity. This interpretative synthesis aims at providing a plausible immunological and immunogenetic model by which BCG vaccination may, in fact, be beneficial for the current efforts in combating COVID-19.

scholarly journals BCG Vaccine Derived Peptides Induce SARS-CoV-2 T Cell Cross-Reactivity

2021 ◽  
Vol 12 ◽  
Author(s):  
Peter J. Eggenhuizen ◽  
Boaz H. Ng ◽  
Janet Chang ◽  
Ashleigh L. Fell ◽  
Rachel M. Y. Cheong ◽  
...  
Keyword(s):  
Clinical Trials ◽  
T Cell ◽  
Epidemiological Studies ◽  
Cross Reactivity ◽  
Bcg Vaccine ◽  
Protective Effects ◽  
Cell Reactivity ◽  
Bcg Vaccination ◽  
T Cell Reactivity

Epidemiological studies and clinical trials suggest Bacillus Calmette-Guérin (BCG) vaccine has protective effects against coronavirus disease 2019 (COVID-19). There are now over 30 clinical trials evaluating if BCG vaccination can prevent or reduce the severity of COVID-19. However, the mechanism by which BCG vaccination can induce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses is unknown. Here, we identify 8 novel BCG-derived peptides with significant sequence homology to either SARS-CoV-2 NSP3 or NSP13-derived peptides. Using an in vitro co-culture system, we show that human CD4+ and CD8+ T cells primed with a BCG-derived peptide developed enhanced reactivity to its corresponding homologous SARS-CoV-2-derived peptide. As expected, HLA differences between individuals meant that not all persons developed immunogenic responses to all 8 BCG-derived peptides. Nevertheless, all of the 20 individuals that were primed with BCG-derived peptides developed enhanced T cell reactivity to at least 7 of 8 SARS-CoV-2-derived peptides. These findings provide an in vitro mechanism that may account, in part, for the epidemiologic observation that BCG vaccination confers some protection from COVID-19.

scholarly journals Gamma-Irradiated Bacille Calmette-Guérin Vaccination Does Not Modulate the Innate Immune Response during Experimental Human Endotoxemia in Adult Males

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Linda A. C. Hamers ◽  
Matthijs Kox ◽  
Rob J. W. Arts ◽  
Bastiaan Blok ◽  
Jenneke Leentjens ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Ex Vivo ◽  
Innate Immune ◽  
Bcg Vaccine ◽  
Controlled Study ◽  
Bacille Calmette Guerin ◽  
Bcg Vaccination ◽  
Gamma Irradiated

Bacille Calmette-Guérin (BCG) vaccine exerts nonspecific immunostimulatory effects and may therefore represent a novel therapeutic option to treat sepsis-induced immunoparalysis. We investigated whether BCG vaccination modulates the systemic innate immune response in humansin vivoduring experimental endotoxemia. We used inactivated gamma-irradiated BCG vaccine because of the potential risk of disseminated disease with the live vaccine in immunoparalyzed patients. In a randomized double-blind placebo-controlled study, healthy male volunteers were vaccinated with gamma-irradiated BCG (n=10) or placebo (n=10) and received 1 ng/kg lipopolysaccharide (LPS) intravenously on day 5 after vaccination to assess thein vivoimmune response. Peripheral blood mononuclear cells were stimulated with various related and unrelated pathogens 5, 8 to 10, and 25 to 35 days after vaccination to assessex vivoimmune responses. BCG vaccination resulted in a scar in 90% of vaccinated subjects. LPS administration elicited a profound systemic immune response, characterized by increased levels of pro- and anti-inflammatory cytokines, hemodynamic changes, and flu-like symptoms. However, BCG modulated neither thisin vivoimmune response, norex vivoleukocyte responses at any time point. In conclusion, gamma-irradiated BCG is unlikely to represent an effective treatment option to restore immunocompetence in patients with sepsis-induced immunoparalysis. This trial is registered withNCT02085590.

scholarly journals Rationale for Randomized Clinical Trials Investigating the Potential of BCG Vaccination in Preventing COVID-19 Infection

2021 ◽  
pp. 1-11
Author(s):  
Magali Noval Rivas ◽  
Charles J. Rosser ◽  
Moshe Arditi
Keyword(s):  
Clinical Trials ◽  
Healthcare Workers ◽  
Randomized Clinical Trials ◽  
Innate Immune ◽  
Bcg Vaccine ◽  
Mitigation Measures ◽  
Medical Care System ◽  
Cancer Data ◽  
Bcg Vaccination ◽  
Frontline Healthcare Workers

Despite the implementation of mitigation measures, Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still spreading worldwide, and has caused more than 1 million deaths so far. Although recent reports indicate that three vaccine candidates are effective against SARS-CoV-2, more time is needed to generate enough doses for the general population. Meanwhile, frontline healthcare workers are at high risk of SARS-CoV-2 exposure. To avoid collapse of the medical care system, there is a need to develop novel approaches to limit SARS-CoV-2 spread. Through a process called trained immunity, the Bacillus Calmette-Guerin (BCG) vaccine boosts the action of innate immune cells, resulting in a nonspecific reduction in the incidence of viral infections. Due to this immunomodulatory action, the BCG vaccine is currently used as a therapeutic in bladder cancer. Data collected from epidemiological and observational studies indicate that BCG vaccination might provide protection against COVID-19. While these observations do not provide evidence of causality and are limited by cofounding and intrinsic biases, it is crucial to explore the hypothesis that BCG vaccination may provide a nonspecific innate immune boost and therefore protect against COVID-19 in randomized controlled clinical trials, particularly for people at higher risk of developing COVID-19, such as frontline healthcare workers.

scholarly journals BCG vaccine derived peptides induce SARS-CoV-2 T cell cross-reactivity

2020 ◽  
Author(s):  
Peter J. Eggenhuizen ◽  
Boaz H. Ng ◽  
Janet Chang ◽  
Ashleigh L. Fell ◽  
Wey Y. Wong ◽  
...  
Keyword(s):  
T Cell ◽  
Epidemiological Studies ◽  
Cross Reactivity ◽  
T Cell Response ◽  
Bcg Vaccine ◽  
Protective Effects ◽  
Cell Reactivity ◽  
Bcg Vaccination ◽  
Mechanistic Basis

AbstractEpidemiological studies suggest that the Bacillus Calmette-Guérin (BCG) vaccine may have protective effects against coronavirus disease 2019 (COVID-19); and, there are now more than 15 ongoing clinical trials seeking to determine if BCG vaccination can prevent or reduce the severity of COVID-19 (1). However, the mechanism by which BCG vaccination can induce a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific T cell response is unknown. Here, in silico, we identify 8 BCG derived peptides with significant sequence homology to either SARS-CoV-2 NSP3 or NSP13 derived peptides. Using an in vitro co-culture system, we show that human CD4+ and CD8+ T cells primed with a BCG derived peptide developed enhanced reactivity to its corresponding SARS-CoV-2 derived peptide. As expected, HLA differences between individuals meant that not all persons developed immunogenic responses to all 8 BCG derived peptides. Nevertheless, all of the 20 individuals that were primed with BCG derived peptides developed enhanced T cell reactivity to at least 7 of 8 SARS-CoV-2 derived peptides. These findings provide a mechanistic basis for the epidemiologic observation that BCG vaccination confers protection from COVID-19; and supports the use of BCG vaccination to induce cross-reactive SARS-CoV-2 specific T cell responses.

Innate immune memory mediates increased susceptibility to Alzheimeŕs disease-like pathology in sepsis surviving mice

2021 ◽  
Author(s):  
Virginia L. De Sousa ◽  
Suzana B. Araújo ◽  
Leticia M. Antonio ◽  
Mariana Silva-Queiroz ◽  
Lilian C. Colodeti ◽  
...  
Keyword(s):  
Innate Immune ◽  
Immune Memory ◽  
Alzheimers Disease ◽  
Increased Susceptibility

scholarly journals The Role of Cell Metabolism in Innate Immune Memory

2020 ◽  
pp. 1-9
Author(s):  
Anaisa Valido Ferreira ◽  
Jorge Domiguéz-Andrés ◽  
Mihai Gheorghe Netea
Keyword(s):  
Metabolic Pathways ◽  
Tricarboxylic Acid Cycle ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Immune Memory ◽  
Functional Changes ◽  
Trained Immunity ◽  
Health And Disease

Immunological memory is classically attributed to adaptive immune responses, but recent studies have shown that challenged innate immune cells can display long-term functional changes that increase nonspecific responsiveness to subsequent infections. This phenomenon, coined <i>trained immunity</i> or <i>innate immune memory</i>, is based on the epigenetic reprogramming and the rewiring of intracellular metabolic pathways. Here, we review the different metabolic pathways that are modulated in trained immunity. Glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, amino acid, and lipid metabolism are interplaying pathways that are crucial for the establishment of innate immune memory. Unraveling this metabolic wiring allows for a better understanding of innate immune contribution to health and disease. These insights may open avenues for the development of future therapies that aim to harness or dampen the power of the innate immune response.

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