Peptide Display Directed Assembly of Biopolymer Core-Silica Shell Particles.

The unique hierarchical core-shell structures of silica capsules contributing to delivery of active compounds have attracted broad interest. To overcome the limited cargo-loading capacity of silica capsules but harness the silica mediated cargo protection, Escherichia coli is engineered to efficiently assemble submicrometer-sized biopolyester particles (BPs) that densely display the positively charged RK1 peptide ((RKK)GY), which mediates nucleation and growth of silica. The peptide-coated BPs are tested as biomimetic template and treatment with silica precursors results in formation of BP core-silica shell structures.

Discovery of ianthelliformisamines D-G from the sponge and the total synthesis of ianthelliformisamine D.

The marine sponge was investigated for new chemistry after the recent discovery that polyamines ianthelliformisamines A-C (-) - originally sourced from this Australian sponge - act as biofilm inhibitors and antibiotic enhancers. Large-scale extraction and isolation studies resulted in the discovery of four new and minor natural products, ianthelliformisamines D-G (-) and the known steroid, aplysterol (). Compounds - were fully characterised following 1D/2D NMR, MS and UV data analyses.

Restructuring Biologically Assembled Binding Protein-Biopolymer Conjugates toward Advanced Materials.

Bacterial cell factories have been successfully engineered to efficiently assemble spherical polyhydroxybutyrate inclusions coated with functional proteins of interest. In these submicrometer-sized core-shell assemblies, proteins are bioconjugated to the polymer core, enabling bioengineering for uses as bioseparation resins, enzyme carriers, diagnostic reagents, and particulate vaccines. Here, we explore whether these functional protein-polymer assemblies could be restructured via dissolution and subsequent precipitation while retaining the functionality of the conjugated protein.

Functionalisation of polyhydroxybutyrate for diagnostic uses.

Polyhydroxybutyrate (PHB) is a biodegradable and biocompatible biopolyester, naturally produced and self-assembled as spherical inclusions inside bacteria. These PHB particles contain a hydrophobic PHB core covalently coated with PHB synthase (PhaC), which serves as an anchoring linker for foreign proteins of interest. Protein engineering of PhaC enables the display of biologically active protein functions on the surface of PHB particles suitable for different applications.

Correction: Soda et al. Electrochemical Detection of Global DNA Methylation Using Biologically Assembled Polymer Beads. 2021, , 3787.

In the original publication [...

Intranasal Epitope-Polymer Vaccine Lodges Resident Memory T Cells Protecting Against Influenza Virus.

Intranasal vaccines, unlike injectable vaccines, boost immunity along the respiratory tract; this can significantly limit respiratory virus replication and shedding. There remains a need to develop mucosal adjuvants and vaccine delivery systems that are both safe and effective following intranasal administration. Here, biopolymer particles (BP) densely coated with repeats of MHC class I restricted immunodominant epitopes derived from influenza A virus namely NP, a nucleoprotein-derived epitope and PA, a polymerase acidic subunit derived epitope, are bioengineered.

In vivo assembly of epitope-coated biopolymer particles that induce anti-tumor responses.

There is an unmet need for antigen delivery systems that elicit efficient T cell priming to prevent infectious diseases or for treatment of cancers. Here, we explored the immunogenic potential of biologically assembled biopolymer particles (BPs) that have been bioengineered to display the antigenic MHC I and MHC II epitopes of model antigen ovalbumin (OVA). Purified dendritic cells (DCs) captured BP-OVA and presented the associated antigenic epitopes to CD4 T cells and CD8 T cells.

Targeting Tumor Heterogeneity with Neoantigen-Based Cancer Vaccines.

Neoantigen-based cancer vaccines have emerged as a promising immunotherapeutic approach to treat cancer. Nevertheless, the high degree of heterogeneity in tumors poses a significant hurdle for developing a vaccine that targets the therapeutically relevant neoantigens capable of effectively stimulating an immune response as each tumor contains numerous unique putative neoantigens. Understanding the complexities of tumor heterogeneity is crucial for the development of personalized neoantigen-based vaccines, which hold the potential to revolutionize cancer treatment and improve patient outcomes.

Evaluation of cell adhesion molecules (LFA-1 and L-selectin) in ankylosing spondylitis patients after treatment with β-D-mannuronic acid (M2000).

Background & Objectives: To examine β-D-mannuronic acid (M2000) effects on L-selectin shedding and leucocyte function-associated antigen-1 (LFA-1) expression as mechanisms of action of this drug in patients with ankylosing spondylitis (AS).

Methods: To investigate the molecular consequences of β-D-mannuronic acid on L-selectin shedding, flow cytometry method was used. Furthermore, the effect of it on LFA-1 gene expression was analyzed by using quantitative real time (qRT)-PCR technique.

Q fever immunology: the quest for a safe and effective vaccine.

Q fever is an infectious zoonotic disease, caused by the Gram-negative bacterium Coxiella burnetii. Transmission occurs from livestock to humans through inhalation of a survival form of the bacterium, the Small Cell Variant, often via handling of animal parturition products. Q fever manifests as an acute self-limiting febrile illness or as a chronic disease with complications such as vasculitis and endocarditis.

Polymeric epitope-based vaccine induces protective immunity against group A Streptococcus.

Group A Streptococcus (Strep A) is a life-threatening human pathogen with no licensed vaccine. Here, we used a biopolymer particle (BP) approach to display repeats of Strep A vaccine candidate peptides p*17 and K4S2 derived from M and non-M protein, respectively. BPs densely displaying both peptides (BP-p*17-S2) were successfully assembled in one-step inside an engineered endotoxin-free Escherichia coli strain.

Bromotyrosine-Derived Metabolites from a Marine Sponge Inhibit Biofilms.

forms stable biofilms, providing a major barrier for multiple classes of antibiotics and severely impairing treatment of infected patients. The biofilm matrix of this Gram-negative bacterium is primarily composed of three major exopolysaccharides: alginate, Psl, and Pel. Here, we studied the antibiofilm properties of sponge-derived natural products ianthelliformisamines A-C and their combinations with clinically used antibiotics.

Precision-engineering of subunit vaccine particles for prevention of infectious diseases.

Vaccines remain the best approach for the prevention of infectious diseases. Protein subunit vaccines are safe compared to live-attenuated whole cell vaccines but often show reduced immunogenicity. Subunit vaccines in particulate format show improved vaccine efficacy by inducing strong immune responses leading to protective immunity against the respective pathogens.

subsp. antigens induce cellular immune responses in cattle without causing reactivity to tuberculin in the tuberculosis skin test.

subspecies (MAP) causes chronic progressive granulomatous enteritis leading to diarrhea, weight-loss, and eventual death in ruminants. Commercially available vaccine provides only partial protection against MAP infection and can interfere with the use of current diagnostic tests for bovine tuberculosis in cattle. Here, we characterized immune responses in calves to vaccines containing four truncated MAP antigens as a fusion (Ag85A-SOD-Ag85B-74F), either displayed on protein particles, or expressed as a soluble recombinant MAP (rMAP) fusion protein as well as to commercially available Silirum vaccine.

Assembly of Immunogenic Protein Particles toward Advanced Synthetic Vaccines.

Immunogenic carrier proteins such as the non-toxic diphtheria toxin variant, cross-reacting material 197 (CRM197), are widely used in subunit vaccine formulations to boost immunogenicity of chemically conjugated antigens. Conjugate vaccines are inherently expensive due to laborious manufacturing steps. Here, this work develops a particulate vaccine platform based on using engineered Escherichia coli to assemble CRM197-antigen fusion proteins into discrete submicron-sized particles.

Cold atmospheric plasma for preventing infection of viruses that use ACE2 for entry.

The mutating SARS-CoV-2 potentially impairs the efficacy of current vaccines or antibody-based treatments. Broad-spectrum and rapid anti-virus methods feasible for regular epidemic prevention against COVID-19 or alike are urgently called for. Using SARS-CoV-2 virus and bioengineered pseudoviruses carrying ACE2-binding spike protein domains, we examined the efficacy of cold atmospheric plasma (CAP) on virus entry prevention.

Intranasal Delivery of Antigen-Coated Polymer Particles Protects against Infection.

is an opportunistic human pathogen that is intrinsically resistant to multiple antibiotics, causing severe and persistent infections in immunocompromised individuals. This bacterium has been listed as a priority pathogen by the WHO in 2017, and there is no vaccine available for human use. In this study, 10 vaccine candidate antigens were selected for particulate vaccine design.

Engineering Antigens to Assemble into Polymer Particle Vaccines for Prevention of Infection.

is a zoonotic pathogen affecting pigs and humans. This bacterium causes severe economic losses in the swine industry and poses a serious threat to public health and food safety. There is no effective commercial vaccine available for pigs or humans.

Epitope-coated polymer particles elicit neutralising antibodies against Plasmodium falciparum sporozoites.

The current Malaria RTS,S vaccine is based on virus-like particles (VLPs) comprising the NANP repetitive epitopes from the cicumsporozoite protein (CSP) of Plasmodium falciparum. This vaccine has limited efficacy, only preventing severe disease in about 30% of vaccinated individuals. A more efficacious vaccine is urgently needed to combat malaria.

Ambient Temperature Stable, Scalable COVID-19 Polymer Particle Vaccines Induce Protective Immunity.

There is an unmet need for safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines that are stable and can be cost-effectively produced at large scale. Here, a biopolymer particle (BP) vaccine technology that can be quickly adapted to new and emerging variants of SARS-CoV-2 is used. Coronavirus antigen-coated BPs are described as vaccines against SARS-CoV-2.

Particulate Mycobacterial Vaccines Induce Protective Immunity against Tuberculosis in Mice.

Currently available vaccines fail to provide consistent protection against tuberculosis (TB). New, improved vaccines are urgently needed for controlling the disease. The mycobacterial antigen fusions H4 (Ag85B-TB10.

Electrochemical Detection of Global DNA Methylation Using Biologically Assembled Polymer Beads.

DNA methylation is a cell-type-specific epigenetic marker that is essential for transcriptional regulation, silencing of repetitive DNA and genomic imprinting. It is also responsible for the pathogenesis of many diseases, including cancers. Herein, we present a simple approach for quantifying global DNA methylation in ovarian cancer patient plasma samples based on a new class of biopolymer nanobeads.

A -Derived Particulate Vaccine Protects against Infection.

Despite numerous efforts to develop an effective vaccine against , no vaccine has yet been approved for human use. This study investigates the utility of the inherently produced polyhydroxyalkanaote (PHA) inclusions and associated host-cell proteins (HCP) as a particulate vaccine platform. We further engineered PHA inclusions to display epitopes derived from the outer membrane proteins OprF/OprI/AlgE (Ag) or the type III secretion system translocator PopB.

Epithelial-to-Mesenchymal Transition Enhances Cancer Cell Sensitivity to Cytotoxic Effects of Cold Atmospheric Plasmas in Breast and Bladder Cancer Systems.

Cold atmospheric plasma (CAP) has emerged as a highly selective anticancer agent, most recently in the form of plasma-activated medium (PAM). Since epithelial-mesenchymal transition (EMT) has been implicated in resistance to various cancer therapies, we assessed whether EMT status is associated with PAM response. Mesenchymal breast cancer cell lines, as well as the mesenchymal variant in an isogenic EMT/MET human breast cancer cell system (PMC42-ET/LA), were more sensitive to PAM treatment than their epithelial counterparts, contrary to their responses to other therapies.