scholarly journals Induction of trained immunity by influenza vaccination - impact on COVID-19

2021 ◽  
Author(s):  
Priya A. Debisarun ◽  
Katharina L. Gössling ◽  
Ozlem Bulut ◽  
Gizem Kilic ◽  
Martijn Zoodsma ◽  
...  
Keyword(s):  
Influenza Vaccination ◽  
Epidemiological Studies ◽  
Innate Immune ◽  
Protective Effects ◽  
Innate Immune Responses ◽  
Dutch Hospital ◽  
Trained Immunity ◽  
Transcriptional Reprogramming ◽  
Potential Benefits

ABSTRACTNon-specific protective effects of certain vaccines have been reported, and long-term boosting of innate immunity, termed trained immunity, has been proposed as one of the mechanisms mediating these effects. Several epidemiological studies suggested cross-protection between influenza vaccination and COVID-19. In a large academic Dutch hospital, we found that SARS-CoV-2 infection was less common among employees who had received a previous influenza vaccination: relative risk reductions of 37% and 49% were observed following influenza vaccination during the first and second COVID-19 waves, respectively. The quadrivalent inactivated influenza vaccine induced a trained immunity program that boosted innate immune responses against various viral stimuli and fine-tuned the anti-SARS-CoV-2 response, which may result in better protection against COVID-19. Influenza vaccination led to transcriptional reprogramming of monocytes and reduced systemic inflammation. These epidemiological and immunological data argue for potential benefits of influenza vaccination against COVID-19, and future randomized trials are warranted to test this possibility.

scholarly journals Induction of trained immunity by influenza vaccination - impact on COVID-19

2021 ◽  
Vol 17 (10) ◽  
pp. e1009928
Author(s):  
Priya A. Debisarun ◽  
Katharina L. Gössling ◽  
Ozlem Bulut ◽  
Gizem Kilic ◽  
Martijn Zoodsma ◽  
...  
Keyword(s):  
Influenza Vaccination ◽  
Epidemiological Studies ◽  
Innate Immune ◽  
Protective Effects ◽  
Innate Immune Responses ◽  
Dutch Hospital ◽  
Trained Immunity ◽  
Transcriptional Reprogramming ◽  
Potential Benefits

Non-specific protective effects of certain vaccines have been reported, and long-term boosting of innate immunity, termed trained immunity, has been proposed as one of the mechanisms mediating these effects. Several epidemiological studies suggested cross-protection between influenza vaccination and COVID-19. In a large academic Dutch hospital, we found that SARS-CoV-2 infection was less common among employees who had received a previous influenza vaccination: relative risk reductions of 37% and 49% were observed following influenza vaccination during the first and second COVID-19 waves, respectively. The quadrivalent inactivated influenza vaccine induced a trained immunity program that boosted innate immune responses against various viral stimuli and fine-tuned the anti-SARS-CoV-2 response, which may result in better protection against COVID-19. Influenza vaccination led to transcriptional reprogramming of monocytes and reduced systemic inflammation. These epidemiological and immunological data argue for potential benefits of influenza vaccination against COVID-19, and future randomized trials are warranted to test this possibility.

scholarly journals The effect of influenza vaccination on trained immunity: impact on COVID-19

2020 ◽  
Author(s):  
Priya A. Debisarun ◽  
Patrick Struycken ◽  
Jorge Domínguez-Andrés ◽  
Simone J.C.F.M. Moorlag ◽  
Esther Taks ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Influenza Vaccination ◽  
Influenza Season ◽  
Winter Season ◽  
Underlying Mechanism ◽  
Epidemiological Studies ◽  
Protective Effects ◽  
Dutch Hospital ◽  
Trained Immunity

ABSTRACTEvery year, influenza causes 290.000 to 650.000 deaths worldwide and vaccination is encouraged to prevent infection in high-risk individuals. Interestingly, cross-protective effects of vaccination against heterologous infections have been reported, and long-term boosting of innate immunity (also termed trained immunity) has been proposed as the underlying mechanism. Several epidemiological studies also suggested cross-protection between influenza vaccination and COVID-19 during the current pandemic. However, the mechanism behind such an effect is unknown. Using an established in-vitro model of trained immunity, we demonstrate that the quadrivalent inactivated influenza vaccine used in the Netherlands in the 2019-2020 influenza season can induce a trained immunity response, including an improvement of cytokine responses after stimulation of human immune cells with SARS-CoV-2. In addition, we found that SARS-CoV-2 infection was less common among Dutch hospital employees who had received influenza vaccination during the 2019/2020 winter season (RR = 0,61 (95% CI, 0.4585 - 0.8195, P = 0.001). In conclusion, a quadrivalent inactivated influenza vaccine can induce trained immunity responses against SARS-CoV-2, which may result in relative protection against COVID-19. These data, coupled with similar recent independent reports, argue for a beneficial effect of influenza vaccination against influenza as well as COVID-19, and suggests its effective deployment in the 2020-2021 influenza season to protect against both infections.

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.

scholarly journals Immunologic Consequences of Hypoxia during Critical Illness

2016 ◽  
Vol 125 (1) ◽  
pp. 237-249 ◽  
Author(s):  
Harmke D. Kiers ◽  
Gert-Jan Scheffer ◽  
Johannes G. van der Hoeven ◽  
Holger K. Eltzschig ◽  
Peter Pickkers ◽  
...  
Keyword(s):  
Immune Responses ◽  
Signaling Pathways ◽  
Daily Practice ◽  
Innate Immune ◽  
Protective Effects ◽  
Innate Immune Responses ◽  
Downstream Signaling ◽  
Pathogen Clearance ◽  
Pharmacologic Modulation ◽  
Oxygen Status

Abstract Hypoxia and immunity are highly intertwined at clinical, cellular, and molecular levels. The prevention of tissue hypoxia and modulation of systemic inflammation are cornerstones of daily practice in the intensive care unit. Potentially, immunologic effects of hypoxia may contribute to outcome and represent possible therapeutic targets. Hypoxia and activation of downstream signaling pathways result in enhanced innate immune responses, aimed to augment pathogen clearance. On the other hand, hypoxia also exerts antiinflammatory and tissue-protective effects in lymphocytes and other tissues. Although human data on the net immunologic effects of hypoxia and pharmacologic modulation of downstream pathways are limited, preclinical data support the concept of tailoring the immune response through modulation of the oxygen status or pharmacologic modulation of hypoxia-signaling pathways in critically ill patients.

scholarly journals Canonical and Noncanonical Autophagy as Potential Targets for COVID-19

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1619 ◽  
Author(s):  
Melissa Bello-Perez ◽  
Isabel Sola ◽  
Beatriz Novoa ◽  
Daniel J. Klionsky ◽  
Alberto Falco
Keyword(s):  
Molecular Mechanisms ◽  
Viral Infections ◽  
Current Knowledge ◽  
Therapeutic Targets ◽  
Innate Immune ◽  
Interacting Proteins ◽  
Innate Immune Responses ◽  
Molecular Machinery ◽  
Autophagy Pathway

The SARS-CoV-2 pandemic necessitates a review of the molecular mechanisms underlying cellular infection by coronaviruses, in order to identify potential therapeutic targets against the associated new disease (COVID-19). Previous studies on its counterparts prove a complex and concomitant interaction between coronaviruses and autophagy. The precise manipulation of this pathway allows these viruses to exploit the autophagy molecular machinery while avoiding its protective apoptotic drift and cellular innate immune responses. In turn, the maneuverability margins of such hijacking appear to be so narrow that the modulation of the autophagy, regardless of whether using inducers or inhibitors (many of which are FDA-approved for the treatment of other diseases), is usually detrimental to viral replication, including SARS-CoV-2. Recent discoveries indicate that these interactions stretch into the still poorly explored noncanonical autophagy pathway, which might play a substantial role in coronavirus replication. Still, some potential therapeutic targets within this pathway, such as RAB9 and its interacting proteins, look promising considering current knowledge. Thus, the combinatory treatment of COVID-19 with drugs affecting both canonical and noncanonical autophagy pathways may be a turning point in the fight against this and other viral infections, which may also imply beneficial prospects of long-term protection.

scholarly journals Characterization of a long-term mouse primary liver 3D tissue model recapitulating innate-immune responses and drug-induced liver toxicity

PLoS ONE ◽  
2020 ◽  
Vol 15 (7) ◽  
pp. e0235745 ◽  
Author(s):  
Ramona Nudischer ◽  
Kasper Renggli ◽  
Andreas Hierlemann ◽  
Adrian B. Roth ◽  
Cristina Bertinetti-Lapatki
Keyword(s):  
Immune Responses ◽  
Liver Toxicity ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Drug Induced ◽  
Tissue Model

scholarly journals Visfatin Serum Levels Predict Mortality in Critically Ill Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Alexander Koch ◽  
Ralf Weiskirchen ◽  
Alexander Krusch ◽  
Jan Bruensing ◽  
Lukas Buendgens ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Serum Levels ◽  
Innate Immune ◽  
Medical Patients ◽  
Innate Immune Responses ◽  
Long Term Follow Up

The adipokine visfatin, also termed pre-B-cell colony-enhancing factor (PBEF), is mainly derived from adipose tissue but has been implicated in the regulation of innate immune responses. We hypothesized that visfatin could be a potential circulating biomarker in critical illness and sepsis. We therefore measured serum levels of visfatin in a cohort of 229 critically ill medical patients upon admission to the intensive care unit (ICU). In comparison to 53 healthy controls, visfatin levels were significantly elevated in medical ICU patients, especially in patients with sepsis. Visfatin serum concentrations were strongly associated with disease severity and organ failure but did not differ between patients with or without obesity or type 2 diabetes. Visfatin levels correlated with biomarkers of renal failure, liver dysfunction, and other adipokines (e.g., resistin, leptin, and adiponectin) in critically ill patients. High visfatin levels at ICU admission indicated an increased mortality, both at the ICU and during long-term follow-up of approximately two years. Our data therefore demonstrate that circulating visfatin is a valuable biomarker for risk and prognosis assessment in critically ill patients. Furthermore, visfatin seems to be involved in the pathogenesis of excessive systemic inflammation, supporting further research on visfatin as a therapeutic target.

scholarly journals Inactivated trivalent influenza vaccination is associated with lower mortality among patients with COVID-19 in Brazil

2020 ◽  
pp. bmjebm-2020-111549 ◽  
Author(s):  
Günther Fink ◽  
Nina Orlova-Fink ◽  
Tobias Schindler ◽  
Sandra Grisi ◽  
Ana Paula S Ferrer ◽  
...  
Keyword(s):  
Influenza Vaccination ◽  
Large Scale ◽  
Sociodemographic Factors ◽  
Intensive Care Treatment ◽  
Protective Effects ◽  
Innate Immune Responses ◽  
Lower Odds ◽  
Hospitalised Patients ◽  
Specific Mortality ◽  
Target Effects

ObjectiveTo estimate associations between trivalent influenza vaccination and COVID-19 mortality as well as severe clinical outcomes among hospitalised patients.DesignRetrospective observational study.SettingThis study was conducted among hospitalised patients with COVID-19 in Brazil.ParticipantsWe analysed all hospitalised patients with COVID-19 with available vaccination information captured in Brazil’s national electronic respiratory infection data system between 1 January 2020 and 23 June 2020.Main outcome measuresThe primary outcomes were age-specific mortality rates of hospitalised patients with COVID-19 with and without recent inactivated trivalent influenza vaccination.ResultsA total of 53 752 clinically confirmed COVID-19 cases were analysed. Controlling for health facility of treatment, comorbidities as well as an extensive range of sociodemographic factors, patients who received a recent influenza vaccine experienced on average 7% lower odds of needing intensive care treatment (95% CI 0.87 to 0.98), 17% lower odds of requiring invasive respiratory support (95% CI 0.77 to 0.88) and 16% lower odds of death (95% CI 0.78 to 0.90). Protective effects were larger when the vaccine was administered after onset of symptoms as well as among younger patients.ConclusionPatients with COVID-19 with recent inactivated influenza vaccination experience significantly better health outcomes than non-vaccinated patients in Brazil. Beneficial off-target effects of influenza vaccination through trained innate immune responses seem plausible and need to be further explored. Large-scale promotion of influenza vaccines seems advisable, especially in populations at high risk for severe COVID-19 disease progression.

scholarly journals Controlled Human Malaria Infection Induces Long-Term Functional Changes in Monocytes

2020 ◽  
Vol 7 ◽  
Author(s):  
Jona Walk ◽  
Farid Keramati ◽  
L. Charlotte J. de Bree ◽  
Rob J. W. Arts ◽  
Bas Blok ◽  
...  
Keyword(s):  
Malaria Infection ◽  
Oxidized Ldl ◽  
Acute Infection ◽  
Innate Immune ◽  
Immune Memory ◽  
Functional Changes ◽  
Human Malaria ◽  
Trained Immunity ◽  
Controlled Human Malaria Infection

Innate immune memory responses (also termed “trained immunity”) have been described in monocytes after BCG vaccination and after stimulation in vitro with microbial and endogenous ligands such as LPS, β-glucan, oxidized LDL, and monosodium urate crystals. However, whether clinical infections are also capable of inducing a trained immunity phenotype remained uncertain. We evaluated whether Plasmodium falciparum infection can induce innate immune memory by measuring monocyte-derived cytokine production from five volunteers undergoing Controlled Human Malaria Infection. Monocyte responses followed a biphasic pattern: during acute infection, monocytes produced lower amounts of inflammatory cytokines upon secondary stimulation, but 36 days after malaria infection they produced significantly more IL-6 and TNF-α in response to various stimuli. Furthermore, transcriptomic and epigenomic data analysis revealed a clear reprogramming of monocytes at both timepoints, with long-term changes of H3K4me3 at the promoter regions of inflammatory genes that remain present for several weeks after parasite clearance. These findings demonstrate an epigenetic basis of trained immunity induced by human malaria in vivo.

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