scholarly journals Recombinant Fasciola hepatica Fatty Acid Binding Protein as a Novel Anti-Inflammatory Biotherapeutic Drug in an Acute Gram-Negative Nonhuman Primate Sepsis Model

2021 ◽  
Vol 9 (3) ◽  
Author(s):  
Jose J. Rosado-Franco ◽  
Albersy Armina-Rodriguez ◽  
Nicole Marzan-Rivera ◽  
Armando G. Burgos ◽  
Natalie Spiliopoulos ◽  
...  
Keyword(s):  
Fatty Acid Binding Protein ◽  
Causes Of Death ◽  
Fasciola Hepatica ◽  
The United States ◽  
Gram Negative Bacteria ◽  
Fatty Acid Binding ◽  
Gram Negative ◽  
Acid Binding Protein ◽  
Sepsis Model ◽  
Effective Use

Sepsis caused by Gram-negative bacteria affects 1.7 million adults annually in the United States and is one of the most important causes of death at intensive care units. Although the effective use of antibiotics has resulted in improved prognosis of sepsis, the pathological and deathly effects have been attributed to the persistent inflammatory cascade.

scholarly journals Recombinant Fasciola hepatica fatty acid binding protein (Fh15) as a novel anti-inflammatory biotherapeutic in an acute gram-negative non-human primate sepsis model

2021 ◽  
Author(s):  
Jose J. Rosado-Franco ◽  
Albersy Armina-Rodriguez ◽  
Nicole Marzan-Rivera ◽  
Armando Burgos ◽  
Natalie Spiliopoulos ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Immune Cell ◽  
Fasciola Hepatica ◽  
Binding Protein ◽  
Rhesus Macaques ◽  
Fatty Acid Binding ◽  
Gram Negative ◽  
Acid Binding Protein ◽  
Anti Inflammatory

Due to their phylogenetic proximity to human, non-human primates (NHP) are considered and adequate choice for basic and pre-clinical model of sepsis. Gram-negative bacteria are the primary causative of sepsis. During infection bacteria continuously release the potent toxin lipopolysaccharide (LPS) into the bloodstream, which triggers an uncontrolled systemic inflammatory response leading to death. Our previous research has demonstrated in vitro and in vivo using a mouse model of septic shock that Fh15, a recombinant variant of Fasciola hepatica fatty acid binding protein, acts as an antagonist of TLR4 suppressing the LPS-induced pro-inflammatory storm. The present study aimed to demonstrate that Fh15 suppress the cytokine storm and other inflammatory markers during the early phase of endotoxemia induced in rhesus macaques by i.v. infusion with lethal doses of live E. coli. Fh15 was administered as isotonic infusion 30 min prior to the bacterial infusion. Among the novel findings reported in this communication, I) Fh15 significantly prevents bacteremia, suppressed LPS levels in plasma and the production of C-reactive protein and procalcitonin, which are key signature of inflammation and bacterial infection, respectively, II) notably reduced the production of pro-inflammatory cytokines, and III) increased innate immune cell populations in blood, which suggest a role in promoting a prolonged steady state in rhesus macaques even in the presence of inflammatory stimuli. THis is the first report demonstrating that a F. hepatica-derived molecule possesses potential as anti-inflammatory drug against endotoxemia in an NHP model.

scholarly journals Fh15 Blocks the Lipopolysaccharide-Induced Cytokine Storm While Modulating Peritoneal Macrophage Migration and CD38 Expression within Spleen Macrophages in a Mouse Model of Septic Shock

mSphere ◽  
2018 ◽  
Vol 3 (6) ◽  
Author(s):  
Marcos J. Ramos-Benitez ◽  
Caleb Ruiz-Jimenez ◽  
Jose J. Rosado-Franco ◽  
Willy D. Ramos-Pérez ◽  
Loyda B. Mendez ◽  
...  
Keyword(s):  
Septic Shock ◽  
Mouse Model ◽  
Fatty Acid Binding Protein ◽  
Fasciola Hepatica ◽  
Gram Negative Bacteria ◽  
Cytokine Storm ◽  
Fatty Acid Binding ◽  
Content Type ◽  
Acid Binding Protein

ABSTRACT Sepsis caused by Gram-negative bacteria is the consequence of an unrestrained infection that continuously releases lipopolysaccharide (LPS) into the bloodstream, which triggers an uncontrolled systemic inflammatory response leading to multiorgan failure and death. After scrutinizing the immune modulation exerted by a recombinant Fasciola hepatica fatty acid binding protein termed Fh15, our group demonstrated that addition of Fh15 to murine macrophages 1 h prior to LPS stimulation significantly suppresses the expression of proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL1-β). The present study aimed to demonstrate that Fh15 could exert a similar anti-inflammatory effect in vivo using a mouse model of septic shock. Among the novel findings reported in this article, (i) Fh15 suppressed numerous serum proinflammatory cytokines/chemokines when injected intraperitoneally 1 h after exposure of animals to lethal doses of LPS, (ii) concurrently, Fh15 increased the population of large peritoneal macrophages (LPMs) in the peritoneal cavity (PerC) of LPS-injected animals, and (iii) Fh15 downregulated the expression on spleen macrophages of CD38, a cell surface ectoenzyme with a critical role during inflammation. These findings present the first evidence that the recombinant parasitic antigen Fh15 is an excellent modulator of the PerC cell content and in vivo macrophage activation, endorsing Fh15’s potential as a drug candidate against sepsis-related inflammatory response. IMPORTANCE Sepsis is a potentially life-threatening complication of an infection. Sepsis is mostly the consequence of systemic bacterial infections leading to exacerbated activation of immune cells by bacterial products, resulting in enhanced release of inflammatory mediators. Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is a critical factor in the pathogenesis of sepsis, which is sensed by Toll-like receptor 4 (TLR4). The scientific community highly pursues the development of antagonists capable of blocking the cytokine storm by blocking TLR4. We report here that a recombinant molecule of 14.5 kDa belonging to the Fasciola hepatica fatty acid binding protein (Fh15) is capable of significantly suppressing the LPS-induced cytokine storm in a mouse model of septic shock when administered by the intraperitoneal route 1 h after a lethal LPS injection. These results suggest that Fh15 is an excellent candidate for drug development against endotoxemia.

A Fasciola hepatica-derived fatty acid binding protein induces protection against schistosomiasis caused by Schistosoma bovis using the adjuvant adaptation (ADAD) vaccination system

2014 ◽  
Vol 145 ◽  
pp. 145-151 ◽  
Author(s):  
Belén Vicente ◽  
Julio López-Abán ◽  
José Rojas-Caraballo ◽  
Luis Pérez del Villar ◽  
George V. Hillyer ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Fasciola Hepatica ◽  
Binding Protein ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Schistosoma Bovis

scholarly journals Protection against Schistosoma mansoni infection using a Fasciola hepatica-derived fatty acid binding protein from different delivery systems

2016 ◽  
Vol 9 (1) ◽  
Author(s):  
Belén Vicente ◽  
Julio López-Abán ◽  
Jose Rojas-Caraballo ◽  
Esther del Olmo ◽  
Pedro Fernández-Soto ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Schistosoma Mansoni ◽  
Fatty Acid Binding Protein ◽  
Fasciola Hepatica ◽  
Binding Protein ◽  
Delivery Systems ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

Adaptive Immune Stimulation Is Required To Obtain High Protection with Fatty Acid Binding Protein Vaccine Candidate Against Fasciola hepatica In Balb/C Mice

2012 ◽  
Vol 98 (3) ◽  
pp. 527-535 ◽  
Author(s):  
Julio López-Abán ◽  
Ana Esteban ◽  
Belén Vicente ◽  
José Rojas-Caraballo ◽  
Esther del Olmo ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Vaccine Candidate ◽  
Fasciola Hepatica ◽  
Binding Protein ◽  
Immune Stimulation ◽  
Protein Vaccine ◽  
Fatty Acid Binding ◽  
Adaptive Immune ◽  
Acid Binding Protein

Immunoprophylaxis against Fasciola hepatica in Rabbits Using a Recombinant Fh15 Fatty Acid-Binding Protein

2001 ◽  
Vol 87 (3) ◽  
pp. 697 ◽  
Author(s):  
P. Casanueva ◽  
G. V. Hillyer ◽  
V. Ramajo ◽  
A. Oleaga ◽  
E. Y. Espinoza ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Fasciola Hepatica ◽  
Binding Protein ◽  
Fatty Acid Binding ◽  
Acid Binding Protein
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