A Polymer-Based Antigen Carrier Activates Two Innate Immune Pathways for Adjuvant-Free Subunit Vaccines.

The activation of multiple Pattern Recognition Receptors (PRRs) has been demonstrated to trigger inflammatory responses and coordinate the host's adaptive immunity during pathogen infections. The use of PRR agonists as vaccine adjuvants has been reported to synergistically induce specific humoral and cellular immune responses. However, incorporating multiple PRR agonists as adjuvants increases the complexity of vaccine design and manufacturing. In this study, we discovered a polymer that can activate both the Toll-like receptor (TLR) pathway and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. The polymer was then conjugated to protein antigens, creating an antigen delivery system for subunit vaccines. Without additional adjuvants, the antigen-polymer conjugates elicited strong antigen-specific humoral and cellular immune responses. Furthermore, the antigen-polymer conjugates, containing the Receptor Binding Domain (RBD) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Protein or the Monkeypox Antigen M1R as the antigens, were found to induce potent antigen-specific antibodies, neutralizing antibodies, and cytotoxic T cells. Immunization with M1R-polymer also resulted in effective protection in a lethal challenge model. In conclusion, this vaccine delivery platform offers an effective, safe, and simple strategy for inducing antigen-specific immunity against infectious diseases.

Electric manipulation on deformation of ionic ferrofluid sessile droplets.

Active electric-driven droplet manipulation in digital microfluidics constitutes a promising domain owing to the unique and programmable wettability inherent in sessile ionic droplets. The coupling between the electric field and flow field enables precise control over wetting characteristics and droplet morphology. This study delves into the deformation phenomena of ionic sessile ferrofluid droplets in ambient air induced by uniform electric fields. Under the assumption of a pinned mode throughout the process, the deformation is characterized by variations in droplet height and contact angle in response to the applied electric field intensity. A numerical model is formulated to simulate the deformation dynamics of ferrofluid droplets, employing the phase field method for tracking droplet deformation. The fidelity of the numerical outcomes is assessed through the validation process, involving a comparison of droplet geometric deformations with corresponding experimental results. The impact of the electric field on the deformation of dielectric droplets is modulated by parameters such as electric field strength and droplet size. Through meticulously designed experiments, the substantial influence of both field strength and droplet size is empirically verified, elucidating the behavior of ionic sessile droplets. Considering the interplay of electric force, viscous force, and interfacial tension, the heightened field intensity is observed to effectively reduce the contact angle, augment droplet height, and intensify internal droplet flow. Under varying electric field conditions, droplets assume diverse shapes, presenting a versatile approach for microfluidic operations. The outcomes of this research hold significant guiding implications for microfluidic manipulation, droplet handling, and sensing applications.

Design and synthesis of aminothiazole based Hepatitis B Virus (HBV) capsid inhibitors.

The capsid assembly is an essential step for Hepatitis B Virus (HBV) life cycle and is an important target for anti-HBV drug development. In this report, we identified a hit compound with aminothiazole structure by the high throughput screening (HTS) which inhibited the interaction of HBV capsid protein within the cells. The structure hopping and SAR studies of the hit compound afforded compound 79 with potent anti-HBV replication activity and good basic drug-like properties. The working mechanism studies showed that compound 79 could bind to the similar binding site of known HBV capsid inhibitor with heteroaryldihydropyrimidine (HAP) scaffold, through similar hydrophobic interactions but with a different hydrogen bond. This compound exerted potent inhibitory effect upon HBV production, either in cell culture or in mice with no obvious acute toxicity. We propose that further development of this compound could lead to novel potent anti-HBV inhibitors that target HBV capsid assembly.