LiveRNA Therapeutics Inc.

Highly pathogenic viruses from family Phenuiviridae , which are mainly transmitted by arthropods, have intermittently sparked epidemics worldwide. In particular, tick-borne bandaviruses, such as severe fever with thrombocytopenia syndrome virus (SFTSV), continue to spread in mountainous areas, resulting in an average mortality rate as high as 10.5%, highlighting the urgency and importance of vaccine development. Here, an mRNA vaccine developed based on the full-length SFTSV glycoprotein, containing both the receptor-binding domain and the fusion domain, was shown to confer complete protection against SFTSV at a very low dose by triggering a type 1 helper T cell-biased cellular immune response in rodents. Moreover, the vaccine candidate elicited long-term immunity and protection against SFTSV for at least 5 months. Notably, it provided complete cross-protection against other bandaviruses, such as the Heartland virus and Guertu virus, in lethal challenge models. Further research revealed that the conserved epitopes among bandaviruses within the full-length SFTSV glycoprotein may facilitate broad-spectrum protection mediated by the cellular immune response. Collectively, these findings demonstrate that the full-length SFTSV glycoprotein mRNA vaccine is a promising vaccine candidate for SFTSV and other bandaviruses, and provide guidance for the development of broad-spectrum vaccines from conserved antigens and epitopes.

Tick-borne bandaviruses, such as SFTSV and Heartland virus, sporadically trigger outbreaks in addition to influenza viruses and coronaviruses, yet there are no specific vaccines or therapeutics against them. mRNA vaccine technology has advantages in terms of enabling in situ expression and triggering cellular immunity, thus offering new solutions for vaccine development against intractable viruses, such as bandaviruses. In this study, we developed a novel vaccine candidate for SFTSV by employing mRNA vaccination technology and using a full-length glycoprotein as an antigen target. This candidate vaccine confers complete and durable protection against SFTSV at a notably low dose while also providing cross-protection against Heartland virus and Guertu virus. This study highlights the prospective value of full-length SFTSV-glycoprotein-based mRNA vaccines and suggests a potential strategy for broad-spectrum bandavirus vaccines.

Fresh-cut potatoes (Solanum tuberosum L.) are a popular food owing to their freshness, convenience, and health benefits. However, they might present a potentially high health risk to consumers during transportation, processing, and marketing. In the current study, 18 essential oils (EOs) were screened to test their antimicrobial activity against Listeria monocytogenes (LM), Salmonella typhimurium (ST), Staphylococcus aureus (SA), and Escherichia coli O157:H7 (EC O157:H7). The antibacterial effectiveness of a chitosan edible coating (EC) containing cinnamon oil was evaluated against microorganisms on fresh-cut potatoes. Fresh-cut potatoes were treated with chitosan EC and chitosan EC containing different concentrations (0, 0.2, 0.4, and 0.6%, v/v) of cinnamon oil, and uncoated samples served as the control. The viability of naturally occurring microorganisms and artificially inoculated LM on fresh-cut potatoes was evaluated, as were the colour, weight loss, and firmness of potatoes, every 4 days for a total of 16 days at 4 °C. The results demonstrate that the inhibition zones of cinnamon, oregano, and pomelo oils were 16.33–30.47 mm, 22.01–31.31 mm, and 21.75–35.18 mm, respectively. The cinnamon oil exhibits the lowest MIC (0.313 μL/mL) for four foodborne pathogens compared with oregano and pomelo oils. The chitosan EC containing 0.2% cinnamon oil effectively maintains the quality of fresh-cut potatoes including inhibiting the browning, preventing the weight loss, and maintaining the firmness. The decline of total plate counts, yeast and mould counts, total coliform counts, lactic acid bacteria count, and Listeria monocytogenes in EC containing 0.2% cinnamon oil were 2.14, 1.92, 0.98, 0.73, and 1.94 log cfu/g, respectively. Therefore, the use of chitosan EC containing cinnamon oil might be a promising approach for the preservation of fresh-cut potatoes.

Immunotherapy using inflammatory cytokines, such as interleukin (IL)-2 and interferon (IFN)-α, has been clinically validated in treating various cancers. However, systemic immunocytokine-based therapies are limited by the short half-life of recombinant proteins and severe dose-limiting toxicities. In this study, we exploited local immunotherapy by intratumoral administration of lipid nanoparticle (LNP)-encapsulated mRNA cocktail encoding cytokines IL-12, IL-7, and IFN-α. The cytokine mRNA cocktail induced tumor regression in multiple syngeneic mouse models and anti-tumor immune memory in one syngeneic mouse model. Additionally, immune checkpoint blockade further enhanced the anti-tumor efficacy of the cytokine mRNAs. Furthermore, human cytokine mRNAs exhibited robust anti-tumor efficacy in humanized mouse tumor models. Mechanistically, cytokine mRNAs induced tumor microenvironment inflammation, characterized by robust T cell infiltration and significant inflammatory cytokine and chemokine production.