Boosting DNA vaccine power by lipid nanoparticles surface engineered with amphiphilic bioresorbable copolymer.

Successful DNA vaccination generally requires the aid of either a viral vector within vaccine components or an electroporation device into the muscle or skin of the host. However, these systems come with certain obstacles, including limited transgene capacity, broad preexisting immunity in humans, and substantial cell death caused by high voltage pulses, respectively. In this study, we repurposed the use of an amphiphilic bioresorbable copolymer (ABC), called PLA-PEG, as a surface engineering agent that conciliates lipid nanoparticles (LNPs) between stability during preparation and biocompatibility post-vaccination.

Omicron-specific mRNA vaccine induced cross-protective immunity against ancestral SARS-CoV-2 infection with low neutralizing antibodies.

The major challenge in COVID-19 vaccine effectiveness is immune escape by SARS-CoV-2 variants. To overcome this, an Omicron-specific messenger RNA (mRNA) vaccine was designed. The extracellular domain of the spike of the Omicron variant was fused with a modified GCN4 trimerization domain with low immunogenicity (TSomi).

Formulation of SARS-CoV-2 Spike Protein with CpG Oligodeoxynucleotides and Squalene Nanoparticles Modulates Immunological Aspects Following Intranasal Delivery.

Nasal spray vaccination is viewed as a promising strategy for inducing both mucosal and systemic protection against respiratory SARS-CoV-2 coronavirus. Toward this goal, a safe and efficacious mucosal adjuvant is necessary for the transportation of the antigen across the mucosal membrane and antigen recognition by the mucosal immune system to generate broad-spectrum immune responses. This study describes the immunological aspects of SARS-CoV-2 spike (S)-protein after being formulated with CpG oligodeoxynucleotides (ODNs) and squalene nanoparticles (termed PELC).

Structure Effect on the Response of ZnGaO Gas Sensor for Nitric Oxide Applications.

We fabricated a gas sensor with a wide-bandgap ZnGaO (ZGO) epilayer grown on a sapphire substrate by metalorganic chemical vapor deposition. The ZGO presented (111), (222) and (333) phases demonstrated by an X-ray diffraction system. The related material characteristics were also measured by scanning electron microscopy, transmission electron microscopy and X-ray photoelectron spectroscopy.

Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated Immunity.

Clinical cases of allergic reaction that are due to excipients containing polyethylene glycol (PEG), a hydrophilic molecule commonly used in drug/vaccine formulations, has attracted much attention in recent years. In order to develop PEG-free adjuvants, we investigated the feasibility of natural ingredients in the human body such as hyaluronic acid in the form of hyaluronic acid-glycine cholesterol (HACH) conjugate as an excipient for vaccine formulation. Interestingly, HACH grafted with ~13 wt.

Assessment of adjuvantation strategy of lipid squalene nanoparticles for enhancing the immunogenicity of a SARS-CoV-2 spike subunit protein against COVID-19.

Vaccination is regarded as the most effective intervention for controlling the coronavirus disease 2019 (COVID-19) pandemic. The objective of this study is to provide comprehensive information on lipid squalene nanoparticle (SQ@NP)-adjuvanted COVID-19 vaccines regarding modulating immune response and enhancing vaccine efficacy. After being adjuvanted with SQ@NP, the SARS-CoV-2 spike (S) subunit protein was intramuscularly (i.

Colloidal Assemblies Composed of Polymeric Micellar/Emulsified Systems Integrate Cancer Therapy Combining a Tumor-Associated Antigen Vaccine and Chemotherapeutic Regimens.

Integrative medicine comprising a tumor-associated antigen vaccine and chemotherapeutic regimens has provided new insights into cancer therapy. In this study, the AB-type diblock copolymers poly(ethylene glycol)-polylactide (PEG-PLA) were subjected to the dispersion of poorly water-soluble molecules in aqueous solutions. The physicochemical behavior of the chemotherapeutic agent DBPR114 in the PEG-PLA-polymeric aqueous solution was investigated by dynamic light scattering (DLS) technology.

Squalene nanoemulsion reinforces mucosal and immunological fingerprints following intravaginal delivery.

This study describes the assessment of mucosal adjuvant activity of a squalene-based nanoemulsion (SQ@NE) following intravaginal delivery in mice. After immunization, a high level of recruitment of CD11b/c granulocytes and F4/80 macrophages was observed in the vaginal mucosal tissues of the mice immunized with a model protein ovalbumin (OVA) formulated with SQ@NE, and then downstream regulated the expression of MHC II and costimulatory molecules CD40 and CD86 on CD11c cells harvested from the associated draining lymph node. With respect to cytotoxic T lymphocyte immunity, the mice immunized with SQ@NE-formulated OVA elicited a high population of OVA-specific CD8 cells in the spleen and increased the secretion of IFN-γ, IL-2 and IL-17 from OVA-restimulated splenocytes compared with those immunized with OVA alone.

Nanoemulsion adjuvantation strategy of tumor-associated antigen therapy rephrases mucosal and immunotherapeutic signatures following intranasal vaccination.

Background: Emulsion adjuvants are a potent tool for effective vaccination; however, the size matters on mucosal signatures and the mechanism of action following intranasal vaccination remains unclear. Here, we launch a mechanistic study to address how mucosal membrane interacts with nanoemulsion of a well-defined size at cellular level and to elucidate the impact of size on tumor-associated antigen therapy.

Methods: The squalene-based emulsified particles at the submicron/nanoscale could be elaborated by homogenization/extrusion.

Morphology and protein adsorption of aluminum phosphate and aluminum hydroxide and their potential catalytic function in the synthesis of polymeric emulsifiers.

Aluminum-containing salts are commonly used as antacids and vaccine adjuvants; however, key features of functional activities remain unclear. Here, we characterized vaccine formulations based on aluminum phosphate and aluminum hydroxide and investigated the respective modes of action linking physicochemical properties and catalytic ability. TEM microscopy indicated that aluminum phosphate gel solutions are amorphous, whereas aluminum hydroxide gel solutions have a crystalline structure consistent with boehmite.

Impact of antigen-adjuvant associations on antigen uptake and antigen-specific humoral immunity in mice following intramuscular injection.

The effect of antigen-adjuvant associations on antigen uptake and antigen-specific humoral immunity is studied in detail. After formulation with a squalene-based double emulsion (referred to as PELC), the protein ovalbumin (OVA) was intramuscularly injected in mice, in either a separation (OVA-PELC), a surface attachment (OVA-PELC) or an encapsulation (OVA-PELC) manner. As an antigen delivery system, a significant increase of OVA-loaded cells migrating into draining lymph nodes (LNs) was detected in the PELC-formulated OVA groups, attachment and encapsulation as well.

NO gas sensor based on ZnGaO epilayer grown by metalorganic chemical vapor deposition.

A gas sensor based on a ZnGaO(ZGO) thin film grown by metalorganic chemical vapor deposition operated under the different temperature from 25 °C to 300 °C is investigated in this study. This sensor shows great sensing properties at 300 °C. The sensitivity of this sensor is 22.

Deep-Ultraviolet Photodetectors Based on Epitaxial ZnGaO Thin Films.

A single-crystalline ZnGaO epilayer was successfully grown on c-plane (0001) sapphire substrate by metal-organic chemical vapor deposition. This epilayer was used as a ternary oxide semiconductor for application in high-performance metal-semiconductor-metal photoconductive deep-ultraviolet (DUV) photodetectors (PDs). At a bias of 5 V, the annealed ZnGaO PDs showed better performance with a considerably low dark current of 1 pA, a responsivity of 86.

Polysorbasome: A Colloidal Vesicle Contoured by Polymeric Bioresorbable Amphiphiles as an Immunogenic Depot for Vaccine Delivery.

To accomplish an innovative vaccine design, there are two key challenges: developing formulations that avoid cold chain shipment and finding a delivery vehicle that is absorbable in vivo. Here, we explored the design and performance of a colloidal vesicle that enabled us to consider both challenges. We used polymeric bioresorbable amphiphiles as surface-active agents for stabilizing oily/aqueous interfaces and formed a colloidal vehicle named polysorbasome (PSS, polymeric absorbable vesicle), without using conventional emulsifiers such as sorbitan esters or their ethoxylates.

Unsaturated Squalene Content in Emulsion Vaccine Adjuvants Plays a Crucial Role in ROS-Mediated Antigen Uptake and Cellular Immunity.

Emulsion-based adjuvants have been demonstrated to be an effective tool in increasing vaccine efficacy. Here, we aimed to launch a mechanistic study on how emulsion adjuvants interact with immune cells and to elucidate the roles of the core oil in vaccine immunogenicity. Our results showed that treatment of dendritic cells (DCs) and splenocytes with a squalene-based emulsion (referred as SqE) induced reactive oxidative species (ROS) production and resulted in an increase in apoptotic and necrotic cells in a concentration- and time-dependent manner.

Degradable emulsion as vaccine adjuvant reshapes antigen-specific immunity and thereby ameliorates vaccine efficacy.

This study describes the feasibility and adjuvant mechanism of a degradable emulsion for tuning adaptive immune responses to a vaccine antigen. We featured a mouse model with ovalbumin (OVA) as the antigen to deepen our understanding of the properties of a degradable emulsion-based adjuvant, dubbed PELC, interacting with immune cells and to elucidate their roles in vaccine immunogenicity in vivo. First, we demonstrated that the emulsion, which is stabilized by an amphiphilic bioresorbable polymer, shows degradation in mimic human body conditions and considerable tolerance in vivo.

Design and Development of Immunomodulatory Antigen Delivery Systems Based on Peptide/PEG-PLA Conjugate for Tuning Immunity.

Cancer vaccines are considered to be a promising tool for cancer immunotherapy. However, a well-designed cancer vaccine should combine a tumor-associated antigen (TAA) with the most effective immunomodulatory agents and/or delivery system to provoke intense immune responses against the TAA. In the present study, we introduced a new approach by conjugating the immunomodulatory molecule LD-indolicidin to the hydrophilic chain end of the polymeric emulsifier poly(ethylene glycol)-polylactide (PEG-PLA), allowing the molecule to be located close to the surface of the resulting emulsion.

Enzymatic stability and immunoregulatory efficacy of a synthetic indolicidin analogue with regular enantiomeric sequence.

Cell-mediated immunity plays a major role in protecting the host from viral infections and tumor challenge. Here, we report the enzymatic stability and adjuvanticity of a peptiomimetic stereoisomer of the bovine neutrophil peptide indolicidin. The analogue, dubbed ld-indolicidin, contains the regular enantiomeric sequence of indolicidin and is synthesized by general stepwise solid-phase strategy.

High performance of Ga-doped ZnO transparent conductive layers using MOCVD for GaN LED applications.

High performance of Ga-doped ZnO (GZO) prepared using metalorganic chemical vapor deposition (MOCVD) was employed in GaN blue light-emitting diodes (LEDs) as transparent conductive layers (TCL). By the post-annealing process, the annealed 800°C GZO films exhibited a high transparency above 97% at wavelength of 450 nm. The contact resistance of GZO decreased with the annealing temperature increasing.

Recombinant lipidated HPV E7 induces a Th-1-biased immune response and protective immunity against cervical cancer in a mouse model.

The E7 oncoprotein of human papillomavirus (HPV) is an ideal target for developing immunotherapeutic strategies against HPV-associated tumors. However, because protein-based immunogens alone are poor elicitors of the cytotoxic T-lymphocyte (CTL) responses, they have been difficult to exploit for therapeutic purposes. In this study, we report that a recombinant lipoprotein consisting of inactive E7 (E7m) biologically linked to a bacterial lipid moiety (rlipo-E7m) induces the maturation of mouse bone marrow-derived dendritic cells through toll-like receptor 2 (TLR2), skews the immune responses toward the Th1 responses and induces E7-specific CTL responses.

Emulsified nanoparticles containing inactivated influenza virus and CpG oligodeoxynucleotides critically influences the host immune responses in mice.

Background: Antigen sparing and cross-protective immunity are regarded as crucial in pandemic influenza vaccine development. Both targets can be achieved by adjuvantation strategy to elicit a robust and broadened immune response. We assessed the immunogenicity of an inactivated H5N1 whole-virion vaccine (A/Vietnam/1194/2004 NIBRG-14, clade 1) formulated with emulsified nanoparticles and investigated whether it can induce cross-clade protecting immunity.

Synthesis and biological activities of 2-amino-1-arylidenamino imidazoles as orally active anticancer agents.

2-Amino-1-arylidenaminoimidazoles, a novel class of orally (po) active microtubule-destabilizing anticancer agents, were synthesized. The compounds were designed from a hit compound identified in a drug discovery platform by using cancer cell-based high throughput screening assay. Selective synthesized compounds exerted cell cytotoxicity against human cancer cells.

Development of multi-phase emulsions based on bioresorbable polymers and oily adjuvant.

Purpose: To enhance the water affinity of W/O emulsion-adjuvanted vaccines, we used three bioresorbable polymers named PEG-b-PLA, PEG-b-PCL, and PEG-b-PLACL as hydrophilic emulsifier to stabilize the interfaces between the oily Montanide ISA 51 adjuvant and the antigen media.

Methods: Polymers were synthesized by ring-opening polymerization of lactide and/or epsilon-caprolactone in the presence of monomethoxy PEG. (1)H NMR and GPC data showed that obtained polymers consisted of 70 wt.

Enhancement of potent antibody and T-cell responses by a single-dose, novel nanoemulsion-formulated pandemic influenza vaccine.

Vaccine shortages are a major obstacle to influenza pandemic preparedness. Increasing vaccine efficiency provides a potentially effective way to overcome this problem. Specifically, using single-dose immunization to induce protective immunity is an attractive approach to emergency/massive vaccination.

Formulation and immunological evaluation of novel vaccine delivery systems based on bioresorbable poly(ethylene glycol)-block-poly(lactide-co-epsilon-caprolactone).

Novel emulsion-type vaccine delivery systems based on the amphiphilic bioresorbable polymer poly(ethylene glycol)-block-poly(lactide-co-epsilon-caprolactone) (PEG-b-PLACL) and selected oils were developed here. Physicochemical characterizations such as stability, a droplet test, microscopic aspects, and in vitro release showed that PEG-b-PLACL-emulsified formulations have several advantages over traditional vaccine adjuvants in that they are stable, reproducible, and homogeneous fine particles with an appropriate size to facilitate the induction of potent immune responses. Different dispersion-type emulsions have provided different release profiles using ovalbumin in model studies.