Nanotechnology-Based Vaccines for Allergen-Specific Immunotherapy: Potentials and Challenges of Conventional and Novel Adjuvants under Research

The increasing prevalence of allergic diseases demands efficient therapeutic strategies for their mitigation. Allergen-specific immunotherapy (AIT) is the only causal rather than symptomatic treatment method available for allergy. Currently, AIT is being administered using immune response modifiers or adjuvants. Adjuvants aid in the induction of a vigorous and long-lasting immune response, thereby improving the efficiency of AIT. The successful development of a novel adjuvant requires a thorough understanding of the conventional and novel adjuvants under development. Thus, this review discusses the potentials and challenges of these adjuvants and their mechanism of action. Vaccine development based on nanoparticles is a promising strategy for AIT, due to their inherent physicochemical properties, along with their ease of production and ability to stimulate innate immunity. Although nanoparticles have provided promising results as an adjuvant for AIT in in vivo studies, a deeper insight into the interaction of nanoparticle–allergen complexes with the immune system is necessary. This review focuses on the methods of harnessing the adjuvant effect of nanoparticles by detailing the molecular mechanisms underlying the immune response, which includes allergen uptake, processing, presentation, and induction of T cell differentiation.

Download Full-text

Diverse Mechanisms of Allergen Specific Immunotherapy

RUDN Journal of Medicine ◽

10.22363/2313-0245-2019-23-3-233-249 ◽

2019 ◽

Vol 23 (3) ◽

pp. 233-249 ◽

Cited By ~ 1

Author(s):

Lacin Cevhertas ◽

Mübeccel Akdis

Keyword(s):

Immune Response ◽

Molecular Mechanisms ◽

Allergen Immunotherapy ◽

Specific Immunotherapy ◽

Prognostic Markers ◽

Recent Literature ◽

Administration Route ◽

Allergen Specific Immunotherapy ◽

Disease Modifying ◽

Disease Modifying Treatment

Allergen immunotherapy (AIT) is widely used to establish a tolerant immune response and it is currently the only disease modifying treatment. There are different routes to administer the allergen, including subcutaneous, sublingual, intralymphatic, epicutaneous, intradermal, and oral and local nasal allergen immunotherapy. Although the optimal administration route depends on the type of allergen, some patients remain unresponsive and so it is important to predict the outcome before and during treatment. Therefore, there is a need to identify candidate prognostic markers for allergen immunotherapy. Herein, we discuss the recent literature on the molecular mechanisms of AIT.

Download Full-text

Identification of Sulfavant A as the First Synthetic TREM2 Ligand Discloses a Homeostatic Response of Dendritic Cells After Receptor Engagement

10.21203/rs.3.rs-1211312/v1 ◽

2022 ◽

Author(s):

Carmela Gallo ◽

Emiliano Manzo ◽

Giusi Barra ◽

Laura Fioretto ◽

Marcello Ziaco ◽

...

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Mhc Class Ii ◽

Molecular Mechanisms ◽

Vaccine Development ◽

Class Ii ◽

Receptor Activation ◽

T Cell Response ◽

Adjuvant Effect ◽

Adjuvant Activity

Abstract The immune response arises from a fine balance of cellular and molecular mechanisms that provide for surveillance, tolerance, and elimination of dangers as pathogens. Improving the quality of the immune response remains a major goal in immunotherapy and vaccine development. Sulfavant A (SULF A) is a sulfolipid that has shown promising adjuvant activity in a cancer vaccine model. Here we report that SULF A is the first synthetic small molecule binding to the Triggering Receptor Expressed on Myeloid cells-2 (TREM2). The receptor engagement initiates an unconventional maturation of Dendritic cells (DCs) leading to upregulation of the Major Histocompatibility Complex class II (MHC Class II) and costimulatory molecules (CD83, CD86, DC54) without release of T helper type 1 (Th1) or 2 (Th2) cytokines. According to a TREM2 mechanism, this response is mediated by SYK-NFAT axis and is compromised by blockade and gene silencing of the receptor. Activation by SULF A preserved the DC functions to excite the allogeneic T cell response, and induced interleukin-10 (IL-10) release after lipopolysaccharide (LPS) stimulation. These results well support the adjuvant effect of SULF A and offer novel insights into the role of TREM2 in the differentiation of an unprecedented DC phenotype (homeDCs) that contributes to the maintenance of immune homeostasis without compromising lymphocyte activation and immunogenic response. The biological function of SULF-A may be of interest in various physiological and pathological processes involving the immune system.

Download Full-text

Characterization of Weissella viridescens UCO-SMC3 as a Potential Probiotic for the Skin: Its Beneficial Role in the Pathogenesis of Acne Vulgaris

Microorganisms ◽

10.3390/microorganisms9071486 ◽

2021 ◽

Vol 9 (7) ◽

pp. 1486

Author(s):

Marcela Espinoza-Monje ◽

Jorge Campos ◽

Eduardo Alvarez Villamil ◽

Alonso Jerez ◽

Stefania Dentice Maidana ◽

...

Keyword(s):

Immune Response ◽

Oral Treatment ◽

Acne Vulgaris ◽

Topical Administration ◽

In Vivo Studies ◽

Mice Model ◽

Cutibacterium Acnes ◽

Snail Helix Aspersa

Previously, we isolated lactic acid bacteria from the slime of the garden snail Helix aspersa Müller and selected Weissella viridescens UCO-SMC3 because of its ability to inhibit in vitro the growth of the skin-associated pathogen Cutibacterium acnes. The present study aimed to characterize the antimicrobial and immunomodulatory properties of W. viridescens UCO-SMC3 and to demonstrate its beneficial effect in the treatment of acne vulgaris. Our in vitro studies showed that the UCO-SMC3 strain resists adverse gastrointestinal conditions, inhibits the growth of clinical isolates of C. acnes, and reduces the adhesion of the pathogen to keratinocytes. Furthermore, in vivo studies in a mice model of C. acnes infection demonstrated that W. viridescens UCO-SMC3 beneficially modulates the immune response against the skin pathogen. Both the oral and topical administration of the UCO-SCM3 strain was capable of reducing the replication of C. acnes in skin lesions and beneficially modulating the inflammatory response. Of note, orally administered W. viridescens UCO-SMC3 induced more remarkable changes in the immune response to C. acnes than the topical treatment. However, the topical administration of W. viridescens UCO-SMC3 was more efficient than the oral treatment to reduce pathogen bacterial loads in the skin, and effects probably related to its ability to inhibit and antagonize the adhesion of C. acnes. Furthermore, a pilot study in acne volunteers demonstrated the capacity of a facial cream containing the UCO-SMC3 strain to reduce acne lesions. The results presented here encourage further mechanistic and clinical investigations to characterize W. viridescens UCO-SMC3 as a probiotic for acne vulgaris treatment.

Download Full-text

The Antitumor Activity of Sodium Selenite Alone and in Combination with Gemcitabine in Pancreatic Cancer: An In Vitro and In Vivo Study

Cancers ◽

10.3390/cancers13133169 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3169

Author(s):

Kevin Doello ◽

Cristina Mesas ◽

Francisco Quiñonero ◽

Gloria Perazzoli ◽

Laura Cabeza ◽

...

Keyword(s):

Pancreatic Cancer ◽

Sodium Selenite ◽

Molecular Mechanisms ◽

Combined Therapy ◽

Significant Inhibition ◽

In Vivo Studies ◽

C57bl Mice ◽

Migration Capacity

Sodium selenite acts by depleting enzymes that protect against cellular oxidative stress. To determine its effect alone or in combination with gemcitabine (GMZ) in pancreatic cancer, we used PANC-1 and Pan02 cell lines and C57BL mice bearing a Pan02-generated tumor. Our results demonstrated a significant inhibition of pancreatic cancer cell viability with the use of sodium selenite alone and a synergistic effect when associated with GMZ. The molecular mechanisms of the antitumor effect of sodium selenite alone involved apoptosis-inducing factor (AIF) and the expression of phospho-p38 in the combined therapy. In addition, sodium selenite alone and in association with GMZ significantly decreased the migration capacity and colony-forming ability, reduced tumor activity in multicellular tumor spheroids (MTS) and decreased sphere formation of cancer stem cells. In vivo studies demonstrated that combined therapy not only inhibited tumor growth (65%) compared to the untreated group but also relative to sodium selenite or GMZ used as monotherapy (up to 40%), increasing mice survival. These results were supported by the analysis of C57BL/6 albino mice bearing a Pan02-generated tumor, using the IVIS system. In conclusion, our results showed that sodium selenite is a potential agent for the improvement in the treatment of pancreatic cancer and should be considered for future human clinical trials.

Download Full-text

Unraveling the neurotoxicity of titanium dioxide nanoparticles: focusing on molecular mechanisms

Beilstein Journal of Nanotechnology ◽

10.3762/bjnano.7.57 ◽

2016 ◽

Vol 7 ◽

pp. 645-654 ◽

Cited By ~ 17

Author(s):

Bin Song ◽

Yanli Zhang ◽

Jia Liu ◽

Xiaoli Feng ◽

Ting Zhou ◽

...

Keyword(s):

Dna Methylation ◽

Titanium Dioxide ◽

Molecular Mechanisms ◽

Titanium Dioxide Nanoparticles ◽

Brain Dysfunction ◽

In Vivo Studies ◽

Cell Components ◽

New Perspective ◽

The Brain

Titanium dioxide nanoparticles (TiO2 NPs) possess unique characteristics and are widely used in many fields. Numerous in vivo studies, exposing experimental animals to these NPs through systematic administration, have suggested that TiO2 NPs can accumulate in the brain and induce brain dysfunction. Nevertheless, the exact mechanisms underlying the neurotoxicity of TiO2 NPs remain unclear. However, we have concluded from previous studies that these mechanisms mainly consist of oxidative stress (OS), apoptosis, inflammatory response, genotoxicity, and direct impairment of cell components. Meanwhile, other factors such as disturbed distributions of trace elements, disrupted signaling pathways, dysregulated neurotransmitters and synaptic plasticity have also been shown to contribute to neurotoxicity of TiO2 NPs. Recently, studies on autophagy and DNA methylation have shed some light on possible mechanisms of nanotoxicity. Therefore, we offer a new perspective that autophagy and DNA methylation could contribute to neurotoxicity of TiO2 NPs. Undoubtedly, more studies are needed to test this idea in the future. In short, to fully understand the health threats posed by TiO2 NPs and to improve the bio-safety of TiO2 NPs-based products, the neurotoxicity of TiO2 NPs must be investigated comprehensively through studying every possible molecular mechanism.

Download Full-text

An Update on the Role of Dietary Phytochemicals in Human Skin Cancer: New Insights into Molecular Mechanisms

Antioxidants ◽

10.3390/antiox9100916 ◽

2020 ◽

Vol 9 (10) ◽

pp. 916 ◽

Cited By ~ 1

Author(s):

Salman Ul Islam ◽

Muhammad Bilal Ahmed ◽

Haseeb Ahsan ◽

Mazharul Islam ◽

Adeeb Shehzad ◽

...

Keyword(s):

Skin Cancer ◽

Human Skin ◽

Cancer Progression ◽

Fruits And Vegetables ◽

Molecular Mechanisms ◽

In Vivo Studies ◽

Skin Malignancy ◽

Dietary Phytochemicals

Human skin is continuously subjected to environmental stresses, as well as extrinsic and intrinsic noxious agents. Although skin adopts various molecular mechanisms to maintain homeostasis, excessive and repeated stresses can overwhelm these systems, leading to serious cutaneous damage, including both melanoma and non-melanoma skin cancers. Phytochemicals present in the diet possess the desirable effects of protecting the skin from damaging free radicals as well as other benefits. Dietary phytochemicals appear to be effective in preventing skin cancer and are inexpensive, widely available, and well tolerated. Multiple in vitro and in vivo studies have demonstrated the significant anti-inflammatory, antioxidant, and anti-angiogenic characteristics of dietary phytochemicals against skin malignancy. Moreover, dietary phytochemicals affect multiple important cellular processes including cell cycle, angiogenesis, and metastasis to control skin cancer progression. Herein, we discuss the advantages of key dietary phytochemicals in whole fruits and vegetables, their bioavailability, and underlying molecular mechanisms for preventing skin cancer. Current challenges and future prospects for research are also reviewed. To date, most of the chemoprevention investigations have been conducted preclinically, and additional clinical trials are required to conform and validate the preclinical results in humans.

Download Full-text

Angiostatic activity of the antitumor cytokine interleukin-21

Blood ◽

10.1182/blood-2007-09-113878 ◽

2008 ◽

Vol 112 (13) ◽

pp. 4940-4947 ◽

Cited By ~ 36

Author(s):

Karolien Castermans ◽

Sebastien P. Tabruyn ◽

Rong Zeng ◽

Judy R. van Beijnum ◽

Cheryl Eppolito ◽

...

Keyword(s):

Immune Response ◽

Tumor Angiogenesis ◽

Chorioallantoic Membrane ◽

Antitumor Immune Response ◽

In Vivo Studies ◽

Type I ◽

Stat3 Phosphorylation ◽

Interleukin 21

Abstract Interleukin-21 (IL-21) is a recently described immunoregulatory cytokine. It has been identified as a very potent immunotherapeutic agent in several cancer types in animal models, and clinical studies are ongoing. IL-21 belongs to the type I cytokine family of which other members, ie, IL-2, IL-15, and IL-4, have been shown to exert activities on vascular endothelial cells (ECs). We hypothesized that IL-21, in addition to inducing the antitumor immune response, also inhibits tumor angiogenesis. In vitro experiments showed a decrease of proliferation and sprouting of activated ECs after IL-21 treatment. We found that the IL-21 receptor is expressed on vascular ECs. Furthermore, in vivo studies in the chorioallantoic membrane of the chick embryo and in mouse tumors demonstrated that IL-21 treatment disturbs vessel architecture and negatively affects vessel outgrowth. Our results also confirm the earlier suggested angiostatic potential of IL-2 in vitro and in vivo. The angiostatic effect of IL-21 is confirmed by the decrease in expression of angiogenesis-related genes. Interestingly, IL-21 treatment of ECs leads to a decrease of Stat3 phosphorylation. Our research shows that IL-21 is a very powerful antitumor compound that combines the induction of an effective antitumor immune response with inhibition of tumor angiogenesis.

Download Full-text

Pleiotropic Biological Effects of Dietary Phenolic Compounds and their Metabolites on Energy Metabolism, Inflammation and Aging

Molecules ◽

10.3390/molecules25030596 ◽

2020 ◽

Vol 25 (3) ◽

pp. 596 ◽

Cited By ~ 3

Author(s):

María del Carmen Villegas-Aguilar ◽

Álvaro Fernández-Ochoa ◽

María de la Luz Cádiz-Gurrea ◽

Sandra Pimentel-Moral ◽

Jesús Lozano-Sánchez ◽

...

Keyword(s):

Energy Metabolism ◽

Phenolic Compounds ◽

Molecular Mechanisms ◽

Biological Effects ◽

Biological Properties ◽

In Vivo Studies ◽

Wide Range ◽

High Prevalence

Dietary phenolic compounds are considered as bioactive compounds that have effects in different chronic disorders related to oxidative stress, inflammation process, or aging. These compounds, coming from a wide range of natural sources, have shown a pleiotropic behavior on key proteins that act as regulators. In this sense, this review aims to compile information on the effect exerted by the phenolic compounds and their metabolites on the main metabolic pathways involved in energy metabolism, inflammatory response, aging and their relationship with the biological properties reported in high prevalence chronic diseases. Numerous in vitro and in vivo studies have demonstrated their pleiotropic molecular mechanisms of action and these findings raise the possibility that phenolic compounds have a wide variety of roles in different targets.

Download Full-text

Yeast as a Model to Understand Actin-Mediated Cellular Functions in Mammals—Illustrated with Four Actin Cytoskeleton Proteins

Cells ◽

10.3390/cells9030672 ◽

2020 ◽

Vol 9 (3) ◽

pp. 672 ◽

Cited By ~ 1

Author(s):

Zain Akram ◽

Ishtiaq Ahmed ◽

Heike Mack ◽

Ramandeep Kaur ◽

Richard C. Silva ◽

...

Keyword(s):

Actin Cytoskeleton ◽

Molecular Mechanisms ◽

Budding Yeast ◽

Animal Cell ◽

Molecular Genetic ◽

In Vivo Studies ◽

Yeast Saccharomyces Cerevisiae ◽

Higher Eukaryotes

The budding yeast Saccharomyces cerevisiae has an actin cytoskeleton that comprises a set of protein components analogous to those found in the actin cytoskeletons of higher eukaryotes. Furthermore, the actin cytoskeletons of S. cerevisiae and of higher eukaryotes have some similar physiological roles. The genetic tractability of budding yeast and the availability of a stable haploid cell type facilitates the application of molecular genetic approaches to assign functions to the various actin cytoskeleton components. This has provided information that is in general complementary to that provided by studies of the equivalent proteins of higher eukaryotes and hence has enabled a more complete view of the role of these proteins. Several human functional homologues of yeast actin effectors are implicated in diseases. A better understanding of the molecular mechanisms underpinning the functions of these proteins is critical to develop improved therapeutic strategies. In this article we chose as examples four evolutionarily conserved proteins that associate with the actin cytoskeleton: (1) yeast Hof1p/mammalian PSTPIP1, (2) yeast Rvs167p/mammalian BIN1, (3) yeast eEF1A/eEF1A1 and eEF1A2 and (4) yeast Yih1p/mammalian IMPACT. We compare the knowledge on the functions of these actin cytoskeleton-associated proteins that has arisen from studies of their homologues in yeast with information that has been obtained from in vivo studies using live animals or in vitro studies using cultured animal cell lines.

Download Full-text

Nutraceuticals for the Treatment of Diabetic Retinopathy

Nutrients ◽

10.3390/nu11040771 ◽

2019 ◽

Vol 11 (4) ◽

pp. 771 ◽

Cited By ~ 20

Author(s):

Maria Grazia Rossino ◽

Giovanni Casini

Keyword(s):

Diabetic Retinopathy ◽

Molecular Mechanisms ◽

Treatment Options ◽

Vitreoretinal Surgery ◽

In Vivo Studies ◽

Early Diabetes ◽

Advanced Stages ◽

Endothelial Growth Factor

Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus and is characterized by degeneration of retinal neurons and neoangiogenesis, causing a severe threat to vision. Nowadays, the principal treatment options for DR are laser photocoagulation, vitreoretinal surgery, or intravitreal injection of drugs targeting vascular endothelial growth factor. However, these treatments only act at advanced stages of DR, have short term efficacy, and cause side effects. Treatment with nutraceuticals (foods providing medical or health benefits) at early stages of DR may represent a reasonable alternative to act upstream of the disease, preventing its progression. In particular, in vitro and in vivo studies have revealed that a variety of nutraceuticals have significant antioxidant and anti-inflammatory properties that may inhibit the early diabetes-driven molecular mechanisms that induce DR, reducing both the neural and vascular damage typical of DR. Although most studies are limited to animal models and there is the problem of low bioavailability for many nutraceuticals, the use of these compounds may represent a natural alternative method to standard DR treatments.

Download Full-text