Protective effects of Surfacen® in allergen-induced asthma mice model

Blanco, Odalys; Ramírez, Wendy; Lugones, Yuliannis; Díaz, Elaine; Morejón, Alain; Rodríguez, Valentín S; Alfonso, Wilma; Labrada, Alexis

doi:10.1016/j.intimp.2021.108391

Cited by 6 publications

(5 citation statements)

References 40 publications

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“…This fraction, named DS1/DS2, contains both major allergens, Der s 1 and Der s 2 at a proportion of 5:1. It was obtained by a purification process in Good Manufacturing Practices (GMPs) conditions ( 20 ), starting from the standardized freeze-dried allergen extract VALERGEN-DS (BIOCEN, Cuba) ( 21 ).…”

Section: Methodsmentioning

confidence: 99%

Immunogenicity of a novel anti-allergic vaccine based on house dust mite purified allergens and a combination adjuvant in a murine prophylactic model

et al. 2022

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The outer-membrane-derived proteoliposome (PL) of Neisseria meningitidis has been reported as a potent vaccine adjuvant, inducing a Th1-skewed response. This work aimed to assess the immunogenicity of a novel anti-allergic vaccine candidate based on allergens from Dermatophagoides siboney house dust mite and a combination adjuvant containing PL and Alum. In a preventative experimental setting, BALB/c mice were administered with three doses containing 2 µg of Der s1 and 0.4 µg Der s2 allergen, PL and Alum, at 7 days intervals, by subcutaneous route. Furthermore, mice were subjected to an allergen aerosol challenge for 6 consecutive days. Serum IgE, IgG1, and IgG2a allergen-specific antibodies were assessed by ELISA. Cytokine levels in supernatants of D. siboney stimulated lymphocyte cultures and in bronchoalveolar lavage (BAL) were measured by ELISA. Lung tissues were subjected to histological examination. The vaccine prevented the development of both, systemic (IgE) and local allergic responses (featuring lower IL-4, and IL-5 levels in BAL) upon allergen exposure by the inhalant route. Histological examination showed also a diminished allergic inflammatory response in the lungs. After the allergen challenge, cytokine levels in stimulated lymphocyte cultures showed lower values of IL-13 and augmented IFN-γ and IL-10. The vaccine induced a mixed IgG2a/IgG1 antibody response; although only IgG2a was PL-dependent. Both, IgG1/IgE and IgG2a/IgE ratios, showed significantly greater values in vaccinated mice. The findings support a preventative anti-allergic effect associated with the induction of a Th1-like IFN-γ/IL-10 response. IgG1/IgE and IgG2a/IgE ratios could be useful biomarkers for translation into clinical trials.

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Section: Methodsmentioning

confidence: 99%

Immunogenicity of a novel anti-allergic vaccine based on house dust mite purified allergens and a combination adjuvant in a murine prophylactic model

et al. 2022

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“…Pulmonary surfactants are a unique mixture of lipids and proteins that create a layer between tissue fluid and inhaled air over the entire surface of pulmonary alveoli (18,21,22). Initially, surfactants were assumed to perform a purely physical (biomechanical) function.…”

Section: Surfactants: General Information On Structure and Functionmentioning

confidence: 99%

“…Increased expression of SP-A and SP-D is associated with a lower frequency and severity of allergic reactions. In contrast, surfactant deficiency enhances allergic immune responses, indicating these molecules' potential role in preventing BA development (18). It is believed that the most important role in the pathogenesis of BA is played precisely by SP-A and SP-D (35).…”

Section: Role Of Surfactants In Immunomodulationmentioning

confidence: 99%

“…The complexity of BA pathogenesis and the instability of response to treatment further emphasize the need for continued research to clarify the pathogenesis and search for new therapeutic targets in this disease. A promising direction in the study of BA pathogenesis is analyzing the role of surfactants, changes in the state of which are considered an aspect of the pathogenesis and diagnosis of the disease, as well as a potential therapeutic target (17)(18)(19). To date, the positive effect of surfactants has been established in several diseases and pathological conditions of the respiratory system, which is believed to be due to their protective properties (20,21).…”

Section: Introductionmentioning

confidence: 99%

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A systematic review of the role of surfactants in bronchial asthma: Implications for pathogenesis and treatment of the disease

Ismailov

2024

Gac Méd Caracas

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The study aims to examine existing literature and highlight the significance of surfactants as a factor in pathogenesis and a potential therapeutic target in bronchial asthma. A systematic search is conducted in Scopus, Web of Science, and PubMed/Medline, utilizing specific keywords related to surfactants and bronchial asthma. The findings demonstrate that surfactants, a unique mixture of lipids and proteins, play a crucial role in the mechanisms of innate and adaptive immunity in the lungs. They act as a mechanical barrier, modulate inflammatory responses, and interact with pathogens. Changes in surfactant composition and levels have been associated with various lung diseases, including bronchial asthma

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“…[20] In addition to its biophysical function, Surfacen has an in vitro anti-infl ammatory eff ect, decreasing tumor necrosis factoralpha (TNF alpha) and interleukin 6 (IL-6), [21] and has shown an anti-infl ammatory and anti-allergic immunomodulatory eff ect in an animal model of allergen-induced asthma. [22] Pulmonary surfactant has been evaluated as a drug carrier or vehicle since the 1990s; [23] it has been used as a budesonide carrier in premature newborns at risk of developing bronchopulmonary dysplasia and is currently undergoing clinical trials. [24,25] Those studies provide the fi rst clinical proof of concept for a surfactant-drug combination and justify research on its possible use in combination therapies with other drugs.…”

Section: Original Researchmentioning

confidence: 99%

Effect of Cuban Porcine Pulmonary Surfactant (Surfacen) and rCmPI-II Protease Inhibitor on Neutrophil Elastase Activity"

et al. 2022

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INTRODUCTIONIn infl ammatory respiratory diseases, the imbalance between proteases and endogenous protease inhibitors leads to an exacerbated activity of human neutrophil elastase (a protease that destroys the extracellular matrix and stimulates proinfl ammatory cytokine release). Elastase is considered a target in the search for therapeutic treatments for infl ammatory respiratory diseases. Pulmonary surfactant is a promising product for this purpose, because in addition to its biophysical function, it has anti-infl ammatory properties.OBJECTIVE Evaluate eff ect of the Cuban porcine pulmonary surfactant (Surfacen), the rCmPI-II elastase inhibitor, and the Surfacen/rCmPI-II combination on activated neutrophil elastase activity in vitro, and determine if Surfacen's interface property changes in the presence of the inhibitor. METHODSThe anti-elastase eff ect of Surfacen, rCmPI-II and the Surfacen/rCmPI-II combination was evaluated in an in vitro model of activated neutrophils, previously purifi ed from the blood of healthy subjects. The cells were stimulated with LPS/fMLP and were incubated with diff erent concentrations of Surfacen, rCmPI-II and the Surfacen/rCmPI-II combination. Elastase activity was measured. The interface property was determined on a Langmuir surface balance. RESULTSSurfacen at 10 mg/mL inhibited 71% of stimulated neutrophil elastase activity. rCmPI-II at 0.1 μM reduced 20% of elastase activity; at 200 μM-the maximum concentration evaluated-inhibition was 68%. Both products had a dosedependent eff ect. The Surfacen/inhibitor combination (0.5 mg/ mL/80 μM) did not aff ect the surfactant interface property or the inhibitory activity of rCmPI-II against human neutrophil elastase.CONCLUSIONS Surfacen and the rCmPI-II inhibitor have an anti-elastase eff ect on an activated neutrophil model. rCmPI-II does not aff ect Surfacen's interface property and, therefore, both can be evaluated for combined use in treating infl ammatory lung diseases.

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Protective effects of Surfacen® in allergen-induced asthma mice model

Cited by 6 publications

References 40 publications

Immunogenicity of a novel anti-allergic vaccine based on house dust mite purified allergens and a combination adjuvant in a murine prophylactic model

Immunogenicity of a novel anti-allergic vaccine based on house dust mite purified allergens and a combination adjuvant in a murine prophylactic model

A systematic review of the role of surfactants in bronchial asthma: Implications for pathogenesis and treatment of the disease

Effect of Cuban Porcine Pulmonary Surfactant (Surfacen) and rCmPI-II Protease Inhibitor on Neutrophil Elastase Activity"

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