Optimizing the synthesis of yeast Beta-glucan via response surface methodology for nanotechnology application.

BACKGROUND: The production of biopolymers from waste resources is a growing trend, especially in high-population countries like Egypt. Beta-glucan (ß-glucan) belongs to natural polysaccharides that are derived from plant and microbial origins. In this study, following increasing demands for ß-glucan owing to its bioactive properties, a statistical model to enhance microbial ß-glucan production was evaluated for its usefulness to the food and pharmaceutical industries. In addition, a trial to convert ß-glucan polymer to nanostructure form was done to increase its bioactivity. RESULTS: Ingredients of low-cost media based on agro-industrial wastes were described using Plackett-Burman and central composite design of response surface methodology for optimizing yeast ß-glucan. Minerals and vitamin concentrations significantly influenced ß-glucan yield for Kluyveromyces lactis and nitrogen and phosphate sources for Meyerozyma guilliermondii. The maximum predicted yields of ß-glucan recovered from K. lactis and M. guilliermondii after optimizing the medium ingredients were 407 and 1188 mg/100 ml; respectively. For the first time, yeast ß-glucan nanoparticles (ßGN) were synthesized from the ß-glucan polymer using N-dimethylformamide as a stabilizer and characterized using UV-vis spectroscopy, transmission electron microscope (TEM), dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FT-IR). The average size of ßGN was about 300 nm as determined by DLS. The quantitative variation of functional groups between ß-glucan polymer and ßGN was evaluated by FT-IR for explaining the difference in their biological activity against Normal Homo sapiens-Hela contaminant and Hepatic cancer cell lines. CONCLUSIONS: Enriching the low-cost media based on agro-industrial wastes with nutritional ingredients improves the yield of yeast ß-glucan. The present study succeeds to form ß-glucan nanoparticles by a simple method.

A "trained immunity" inducer-adjuvanted nanovaccine reverses the growth of established tumors in mice.

Innate immune cells are critical in antitumor immune surveillance and the development of antitumor adaptive cellular immunity. Trained innate immune cells demonstrate immune memory-like characteristics, producing more vigorous immune responses to secondary homologous or heterologous stimuli. This study aimed to investigate whether inducing trained immunity is beneficial when using a tumor vaccine to promote antitumor adaptive immune responses. A biphasic delivery system was developed with the trained immunity inducer Muramyl Dipeptide (MDP) and specific tumor antigen human papillomavirus (HPV) E7 peptide encapsulated by poly(lactide-co-glycolide)-acid(PLGA) nanoparticles (NPs), and the NPs along with another trained immunity agonist, ß-glucan, were further embedded in a sodium alginate hydrogel. The nanovaccine formulation demonstrated a depot effect for E7 at the injection site and targeted delivery to the lymph nodes and dendritic cells (DCs). The antigen uptake and maturation of DCs were significantly promoted. A trained immunity phenotype, characterized by increased production of IL-1ß, IL-6, and TNF-α, was induced in vitro and in vivo in response to secondary homologous or heterologous stimulation. Furthermore, prior innate immune training enhanced the antigen-specific INF-γ-expressing immune cell response elicited by subsequent stimulation with the nanovaccine. Immunization with the nanovaccine completely inhibited the growth of TC-1 tumors and even abolished established tumors in mice. Mechanistically, the inclusion of ß-glucan and MDP significantly enhanced the responses of tumor-specific effector adaptive immune cells. The results strongly suggest that the controlled release and targeted delivery of an antigen and trained immunity inducers with an NP/hydrogel biphasic system can elicit robust adaptive immunity, which provides a promising tumor vaccination strategy.

A vaccine delivery system promotes strong immune responses against SARS-CoV-2 variants.

Global coronavirus disease 2019 (COVID-19) pandemics highlight the need of developing vaccines with universal and durable protection against emerging SARS-CoV-2 variants. Here we developed an extended-release vaccine delivery system (GP-diABZI-RBD), consisting the original SARS-CoV-2 WA1 strain receptor-binding domain (RBD) as the antigen and diABZI stimulator of interferon genes (STING) agonist in conjunction with yeast ß-glucan particles (GP-diABZI) as the platform. GP-diABZI-RBD could activate STING pathway and inhibit SARS-CoV-2 replication. Compared to diABZI-RBD, intraperitoneal injection of GP-diABZI-RBD elicited robust cellular and humoral immune responses in mice. Using SARS-CoV-2 GFP/ΔN transcription and replication-competent virus-like particle system (trVLP), we demonstrated that GP-diABZI-RBD-prototype vaccine exhibited the strongest and durable humoral immune responses and antiviral protection; whereas GP-diABZI-RBD-Omicron displayed minimum neutralization responses against trVLP. By using pseudotype virus (PsVs) neutralization assay, we found that GP-diABZI-RBD-Prototype, GP-diABZI-RBD-Delta, and GP-diABZI-RBD-Gamma immunized mice sera could efficiently neutralize Delta and Gamma PsVs, but had weak protection against Omicron PsVs. In contrast, GP-diABZI-RBD-Omicron immunized mice sera displayed the strongest neutralization response to Omicron PsVs. Taken together, the results suggest that GP-diABZI can serve as a promising vaccine delivery system for enhancing durable humoral and cellular immunity against broad SARS-CoV-2 variants. Our study provides important scientific basis for developing SARS-CoV-2 VOC-specific vaccines.

Primary care experience on Stimunex® gocce in children with recurrent respiratory infections: a real-world study during the COVID-19 pandemic era.

BACKGROUND: Respiratory infections (RI) significantly burden society, mainly when there are recurrent respiratory infections (RRI). Thus, there is a need to prevent RI in clinical practice. In this regard, the modulation of the immune system and resolution of the inflammatory cascade could represent an ideal way to prevent RI. Stimunex® gocce, a multicomponent food supplement, contains Sambucus nigra extract, ß-glucan, Zinc, and Vitamin D3. This study investigated its ability to prevent RRI in children using a real-world setting: the pediatric primary care. MATERIALS AND METHODS: Two hundred and ninety-eight children with RRI were enrolled in the current study. The food supplement was randomly prescribed to 160 children with RRI daily for 4 months (Active group); the remaining 138 children with RRI were treated only with standard therapy for RI (Control group). The number and duration of RI, parental perception of symptom severity and treatment efficacy, use of medications, and school and working absence were evaluated. RESULTS: Children treated with Stimunex® gocce had significantly less RI than the Control group, both concerning upper and lower RI (p˂0.001 and 0.003, respectively) during the follow-up period. Moreover, children in the Active group experienced shorter RI duration during the treatment and follow-up phases (p˂0.001 for both). In addition, parents of treated children perceived less severe symptoms and better treatment efficacy during the first and follow-up phases (p˂0.001 for all). The food supplement was well tolerated and there was no adverse event. CONCLUSIONS: The current real-world study demonstrated that Stimunex® gocce supplementation in children with RRI might safely prevent RI episodes and reduce RI duration. These outcomes should be highlighted as obtained during the COVID-19 pandemic era, characterized by a dramatic reduction of RI.

A concise review of mushrooms antiviral and immunomodulatory properties that may combat against COVID-19.

The World Health Organization (WHO) declared COVID-19 as a pandemic on March 11, 2020, because of its widespread transmission and infection rates. The unique severe disease was found in Wuhan, China, since December 2019, and swiftly spread throughout the world. Natural chemicals derived from herbal medicines and medicinal mushrooms provide a significant resource for the development of novel antiviral drugs. Many natural drugs have been proven to have antiviral properties against a variety of virus strains, such as the coronavirus and the herpes simplex virus (HSV).. In this research, successful dietary treatments for different COVID illnesses were compared to potential of mushroom products in its therapy. In Google Scholar, Science Direct, PubMed, and Scopus, search keywords like COVID, COVID-19, SARS, MERS, mushrooms, and their compounds were utilized. In this review of the literature we foucsed popular mushrooms such as Agaricus subrufescens Peck, Agaricus blazei Murill, Cordyceps sinensis (Berk.) Sacc., Ganoderma lucidum (Curtis.) P. Karst., Grifola frondosa (Dicks.) Gray, Hericium erinaceus (Bull.) Pers., Inonotus obliquus (Arch. Ex Pers.) Pilát., Lentinula edodes (Berk.) Pegler, Pleurotus ostreatus (Jacq.) P. Kumm., Poria cocos F.A. Wolf, and Trametes versicolor (L.) Lloyd.,. Changed forms of ß-Glucan seem to have a good impact on viral replication suppression and might be used in future studies. However, the results seems terpenoids, lectins, glycoproteins, lentinan, galactomannan, and polysaccharides from mushrooms are promising prophylactic or therapeutic agents against COVID-19.

Chitosan, alginate, hyaluronic acid, gums, and ß-glucan as potent adjuvants and vaccine delivery systems for viral threats including SARS-CoV-2: A review.

Pathogen transmission is a widespread threat to global human health. Vaccines are very important during the outbreak of a pandemic. Destructive fractures caused by a sudden outbreak of COVID-19 have spurred vaccine production at an unprecedented rate. The strategy of an effective vaccine delivery system is opening up novel probabilities to make more immunization. Indeed, vaccination is the most successful way to prevent deaths from infectious diseases. In order to optimal immune response production or improvement in the effectiveness of vaccines, delivery systems or adjuvants are required. Natural polymers such as chitosan, alginate, hyaluronic acid, gums, and ß-glucan with antiviral activity have good potential as adjuvant or delivery systems for vaccine formulation development and design vaccine delivery devices. According to the antiviral performance and immunomodulation of these biopolymers, they will play significant characters in the anti-COVID-19 field. In this mini-review, the recent progress in vaccine development by using biopolymers is presented which, provides a reference for their research on anti-COVID-19 drugs and vaccines.

Could the Induction of Trained Immunity by ß-Glucan Serve as a Defense Against COVID-19?

As the SARS-CoV-2 virus wreaks havoc on the populations, health care infrastructures and economies of nations around the world, finding ways to protect health care workers and bolster immune responses in the general population while we await an effective vaccine will be the difference between life and death for many people. Recent studies show that innate immune populations may possess a form of memory, termed Trained Immunity (TRIM), where innate immune cells undergo metabolic, mitochondrial, and epigenetic reprogramming following exposure to an initial stimulus that results in a memory phenotype of enhanced immune responses when exposed to a secondary, heterologous, stimulus. Throughout the literature, it has been shown that the induction of TRIM using such inducers as the BCG vaccine and ß-glucan can provide protection through altered immune responses against a range of viral infections. Here we hypothesize a potential role for ß-glucan in decreasing worldwide morbidity and mortality due to COVID-19, and posit several ideas as to how TRIM may actually shape the observed epidemiological phenomena related to COVID-19. We also evaluate the potential effects of ß-glucan in relation to the immune dysregulation and cytokine storm observed in COVID-19. Ultimately, we hypothesize that the use of oral ß-glucan in a prophylactic setting could be an effective way to boost immune responses and abrogate symptoms in COVID-19, though clinical trials are necessary to confirm the efficacy of this treatment and to further examine differential effects of ß-glucan's from various sources.