Investigation of Biodegradation, Artificial Aging and Antibacterial Properties of Poly(Butylene Succinate) Biocomposites with Onion Peels and Wheat Bran.

The present article focuses on the characterization of the new biocomposites of poly(butylene succinate) (PBS) with fillers of plant origin such as onion peels (OP) and durum wheat bran WB () subjected to composting and artificial aging. The susceptibility to fungal growth, cytotoxicity and antibacterial properties were also examined. The biodegradation of the samples was investigated under normalized conditions simulating an intensive aerobic composting process.

Immunotherapy with biodegradable nanoparticles encapsulating the oligosaccharide galactose-alpha-1,3-galactose enhance immune tolerance against alpha-gal sensitization in a murine model of alpha-gal syndrome.

IgE antibodies against the mammalian oligosaccharide allergen galactose-α-1,3-galactose (αGal) can result in a severe allergic disease known as alpha-gal syndrome (AGS). This syndrome, acquired by tick bites that cause αGal sensitization, leads to allergic reactions after ingestion of non-primate mammalian meat and mammalian-derived products that contain αGal. Allergen-specific immunotherapies for this tickborne allergic syndrome are understudied, as are the immune mechanisms of allergic desensitization that induce clinical tolerance to αGal.

Enhanced mucosal B- and T-cell responses against SARS-CoV-2 after heterologous intramuscular mRNA prime/intranasal protein boost vaccination with a combination adjuvant.

Current COVID-19 mRNA vaccines delivered intramuscularly (IM) induce effective systemic immunity, but with suboptimal immunity at mucosal sites, limiting their ability to impart sterilizing immunity. There is strong interest in rerouting immune responses induced in the periphery by parenteral vaccination to the portal entry site of respiratory viruses, such as SARS-CoV-2, by mucosal vaccination. We previously demonstrated the combination adjuvant, NE/IVT, consisting of a nanoemulsion (NE) and an RNA-based RIG-I agonist (IVT) induces potent systemic and mucosal immune responses in protein-based SARS-CoV-2 vaccines administered intranasally (IN).

A novel intranasal peptide vaccine inhibits non-small cell lung cancer with KRAS mutation.

KRAS mutations occur commonly in the lung and can lead to the development of non-small cell lung cancer (NSCLC). While the mutated KRAS protein is a neoantigen, it usually does not generate an effective anti-tumor immune response on mucosal/epithelial surfaces. Despite this, mutated KRAS remains a potential target for immunotherapy since immune targeting of this protein in animal models has been effective at eliminating tumor cells.

Multicomponent intranasal adjuvant for mucosal and durable systemic SARS-CoV-2 immunity in young and aged mice.

Multiple FDA-approved SARS-CoV-2 vaccines currently provide excellent protection against severe disease. Despite this, immunity can wane relatively fast, particularly in the elderly and novel viral variants capable of evading infection- and vaccination-induced immunity continue to emerge. Intranasal (IN) vaccination more effectively induces mucosal immune responses than parenteral vaccines, which would improve protection and reduce viral transmission.

A multicomponent intranasal adjuvant drives durable humoral, cellular, and mucosal immune responses to SARS-CoV-2 in young and aged mice.

Multiple FDA-approved SARS-CoV-2 vaccines provide excellent protection against severe disease. Despite this, immunity can wane relatively fast, particularly in the elderly and novel viral variants capable of evading infection- and vaccination-induced immunity continue to emerge. Intranasal (IN) vaccination more effectively induces mucosal immune responses than parenteral vaccines, which would improve protection and reduce viral transmission.

Masked Delivery of Allergen in Nanoparticles Safely Attenuates Anaphylactic Response in Murine Models of Peanut Allergy.

Food allergy is a growing health concern worldwide. Current allergen-specific immunotherapy (AIT) approaches require frequent dosing over extended periods of time and may induce anaphylaxis due to allergen-effector cell interactions. A critical need remains to develop novel approaches that refine AIT for the treatment of food allergies.

Targeted allergen-specific immunotherapy within the skin improves allergen delivery to induce desensitization to peanut.

Epicutaneous immunotherapy (EPIT) with peanut has been demonstrated to be safe but efficacy may be limited by allergen uptake through the skin barrier. To enhance allergen uptake into the skin, the authors used peanut-coated microneedles and compared them with EPIT in a peanut allergy mouse model. Sensitized mice were treated with peanut-coated microneedles or peanut-EPIT and then challenged with peanut to determine protection.

A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine.

Several SARS-CoV-2 vaccines have received EUAs, but many issues remain unresolved, including duration of conferred immunity and breadth of cross-protection. Adjuvants that enhance and shape adaptive immune responses that confer broad protection against SARS-CoV-2 variants will be pivotal for long-term protection as drift variants continue to emerge. We developed an intranasal, rationally designed adjuvant integrating a nanoemulsion (NE) that activates TLRs and NLRP3 with an RNA agonist of RIG-I (IVT DI).

Bactericidal and Fungistatic Properties of LDPE Modified with a Biocide Containing Metal Nanoparticles.

The aim of this study was to ascertain whether the combined action of metal nanoparticles (silver, copper, zinc oxide, iron oxide) would ensure the appropriate biocidal properties oflow-density polyethylene (LDPE) against pathogenic microorganisms. According to the research hypothesis, appropriately selected concentrations of the applied metal nanoparticles allow for a high level of biocidal activity of polymeric materials against both model and pathogenic bacterial strains (, , , , subsp. ) and fungi (, , , ), whilst ensuring the safety of use due to the lack of migration of particles to the surrounding environment.

Intranasal delivery of allergen in a nanoemulsion adjuvant inhibits allergen-specific reactions in mouse models of allergic airway disease.

Background: Atopic diseases are an increasing problem that involve both immediate hypersensitivity reactions mediated by IgE and unique cellular inflammation. Many forms of specific immunotherapy involve the administration of allergen to suppress allergic immune responses but are focused on IgE-mediated reactions. In contrast, the effect of allergen-specific immunotherapy on allergic inflammation is complex, not entirely consistent and not well understood.

Combined use of strains and Miscanthus for accelerating biodegradation of poly(lactic acid) and poly(ethylene terephthalate).

Background: The aim of this study was to verify whether the presence of strains and of miscanthus influence biodegradation and formed of biofilm of poly(lactic acid) (PLA) and poly(ethylene terephthalate) (PET).

Methods: The experiment conducted in compost soil showed that strains and isolated from heavy metal contaminated environment have biochemical activity and accelerate biodegradation of both plastic materials.

Results: For PLA film it was found that the carbonyl index dropped by over 15% in the presence of , while the film tensile strength decreased by 35% and the oxygen to carbon O/C ratio was higher by 3% in the presence of , and the presence of miscanthus resulted in a loss of weight.

Mucosal Nanoemulsion Allergy Vaccine Suppresses Alarmin Expression and Induces Bystander Suppression of Reactivity to Multiple Food Allergens.

We have demonstrated that intranasal immunotherapy with allergens formulated in a nanoemulsion (NE) mucosal adjuvant suppresses Th2/IgE-mediated allergic responses and protects from allergen challenge in murine food allergy models. Protection conferred by this therapy is associated with strong suppression of allergen specific Th2 cellular immunity and increased Th1 cytokines. Here we extend these studies to examine the effect of NE-allergen immunization in mice sensitized to multiple foods.

A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine.

Several SARS-CoV-2 vaccines have received EUAs, but many issues remain unresolved, including duration of conferred immunity and breadth of cross-protection. Adjuvants that enhance and shape adaptive immune responses that confer broad protection against SARS-CoV-2 variants will be pivotal for long-term protection. We developed an intranasal, rationally designed adjuvant integrating a nanoemulsion (NE) that activates TLRs and NLRP3 with an RNA agonist of RIG-I (IVT DI).

Combined Intranasal Nanoemulsion and RIG-I Activating RNA Adjuvants Enhance Mucosal, Humoral, and Cellular Immunity to Influenza Virus.

Current influenza virus vaccines are focused on humoral immunity and are limited by the short duration of protection, narrow cross-strain efficacy, and suboptimal immunogenicity. Here, we combined two chemically and biologically distinct adjuvants, an oil-in-water nanoemulsion (NE) and RNA-based agonists of RIG-I, to determine whether the diverse mechanisms of these adjuvants could lead to improved immunogenicity and breadth of protection against the influenza virus. NE activates TLRs, stimulates immunogenic apoptosis, and enhances cellular antigen uptake, leading to a balanced T1/T2/T17 response when administered intranasally.

Intranasal nanoemulsion vaccine confers long-lasting immunomodulation and sustained unresponsiveness in a murine model of milk allergy.

Background: Immunotherapy for food allergy requires prolonged treatment protocols and, in most cases, does not lead to durable modulation of the allergic immune response. We have demonstrated an intranasal (IN) nanoemulsion adjuvant that redirects allergen-specific Th2 responses toward Th1 and Th17 immunity, and protects from allergen challenge after only 2-4 monthly administrations. Here, we investigate the ability of this technology to provide long-term modulation of allergy in a murine model of cow's milk allergy.

Nanoemulsion adjuvant-driven redirection of T2 immunity inhibits allergic reactions in murine models of peanut allergy.

Background: Immunotherapy for food allergies involves progressive increased exposures to food that result in desensitization to food allergens in some subjects but not tolerance to the food. Therefore new approaches to suppress allergic immunity to food are necessary. Previously, we demonstrated that intranasal immunization with a nanoemulsion (NE) adjuvant induces robust mucosal antibody and T17-polarized immunity, as well as systemic T1-biased cellular immunity with suppression of pre-existing T2-biased immunity.

Immunomodulation of TH2 biased immunity with mucosal administration of nanoemulsion adjuvant.

TH2-biased immune responses are associated with inadequate protection against some pathogens and with cancer, colitis, asthma and allergy. Since most currently used vaccine adjuvants induce a TH2-biased response, this has led to interest in developing adjuvants capable of activating TH1 immunity and modulating existing TH2 responses. Immunotherapies to shift immune responses from TH2 to TH1 have generally required prolonged immunization protocols and have not induced effective TH1 responses.

Formulation, high throughput in vitro screening and in vivo functional characterization of nanoemulsion-based intranasal vaccine adjuvants.

Vaccine adjuvants have been reported to induce both mucosal and systemic immunity when applied to mucosal surfaces and this dual response appears important for protection against certain pathogens. Despite the potential advantages, however, no mucosal adjuvants are currently approved for human use. Evaluating compounds as mucosal adjuvants is a slow and costly process due to the need for lengthy animal immunogenicity studies.

Distinct pathways of humoral and cellular immunity induced with the mucosal administration of a nanoemulsion adjuvant.

Nasal administration of an oil-in-water nanoemulsion (NE) adjuvant W805EC produces potent systemic and mucosal, Th-1- and Th-17-balanced cellular responses. However, its molecular mechanism of action has not been fully characterized and is of particular interest because NE does not contain specific ligands for innate immune receptors. In these studies, we demonstrate that W805EC NE adjuvant activates innate immunity, induces specific gene transcription, and modulates NF-κB activity via TLR2 and TLR4 by a mechanism that appears to be distinct from typical TLR agonists.

Nanoemulsion mucosal adjuvant uniquely activates cytokine production by nasal ciliated epithelium and induces dendritic cell trafficking.

While the nasal mucosa is a potentially useful site for human immunization, toxin-based nasal adjuvants are generally unsafe and less effective in humans. Safe mucosal adjuvants that activate protective immunity via mucosal administration are highly dependent on barrier antigen sampling by epithelial and DCs. Here, we demonstrate that protein antigens formulated in unique oil-in-water nanoemulsions (NEs) result in distinctive transcellular antigen uptake in ciliated nasal epithelial cells, leading to delivery into nasal associated lymphoid tissue.

Induction of Th17 cellular immunity with a novel nanoemulsion adjuvant.

T17 (T-helper-17) cytokine responses have been recently recognized as an important component for the protective immunity produced by vaccination. However, the mechanism by which immune adjuvants induce T17 immunity has not been defined. We have developed a novel mucosal nanoemulsion (NE) adjuvant that produces a robust humoral and T1 cellular immunity.

Pre-clinical evaluation of a novel nanoemulsion-based hepatitis B mucosal vaccine.

Background: Hepatitis B virus infection remains an important global health concern despite the availability of safe and effective prophylactic vaccines. Limitations to these vaccines include requirement for refrigeration and three immunizations thereby restricting use in the developing world. A new nasal hepatitis B vaccine composed of recombinant hepatitis B surface antigen (HBsAg) in a novel nanoemulsion (NE) adjuvant (HBsAg-NE) could be effective with fewer administrations.