Inactivated vaccine with glycyrrhizic acid adjuvant elicits potent innate and adaptive immune responses against foot-and-mouth disease

BackgroundFoot-and-mouth disease (FMD) is an extremely contagious viral disease that is fatal to young animals and is a major threat to the agricultural economy by reducing production and limiting the movement of livestock. The currently commercially-available FMD vaccine is prepared using an inactivated viral antigen in an oil emulsion, with aluminum hydroxide [Al(OH)3] as an adjuvant. However, oil emulsion-based options possess limitations including slow increases in antibody titers (up to levels adequate for defense against viral infection) and risks of local reactions at the vaccination site. Further, Al(OH)3 only induces a T helper 2 (Th2) cell response. Therefore, novel adjuvants that can address these limitations are urgently needed. Glycyrrhizic acid (extracted from licorice roots) is a triterpenoid saponin and has great advantages in terms of price and availability.MethodsTo address the limitations of the currently used commercial FMD vaccine, we added glycyrrhizic acid as an adjuvant (immunostimulant) to the FMD bivalent (O PA2 + A YC) vaccine. We then evaluated its efficacy in promoting both innate and adaptive (cellular and humoral) immune reactions in vitro [using murine peritoneal exudate cells (PECs) and porcine peripheral blood mononuclear cells (PBMCs)] and in vivo (using mice and pigs).ResultsGlycyrrhizic acid has been revealed to induce an innate immune response and enhance early, mid-, and long-term immunity. The studied bivalent vaccine with glycyrrhizic acid increased the expression of immunoregulatory genes such as pattern-recognition receptors (PRRs), cytokines, transcription factors, and co-stimulatory molecules.ConclusionCollectively, glycyrrhizic acid could have utility as a novel vaccine adjuvant that can address the limitations of commercialized FMD vaccines by inducing potent innate and adaptive immune responses

Catecholamines May Play an Important Role in the Pathogenesis of Transient Mid- and Basal Ventricular Ballooning Syndrome

The exact pathogenesis of transient mid- and basal ventricular ballooning, a new variant of transient left ventricular (LV) ballooning, remains unknown. We report two cases of transient mid- and basal ventricular ballooning associated with catecholamines. These cases suggest that catecholamine-mediated myocardial dysfunction might be a potential mechanism of this syndrome

Dectin-1 signaling coordinates innate and adaptive immunity for potent host defense against viral infection

BackgroundMost commercial foot-and-mouth disease (FMD) vaccines have various disadvantages, such as low antibody titers, short-lived effects, compromised host defense, and questionable safety.ObjectivesTo address these shortcomings, we present a novel FMD vaccine containing Dectin-1 agonist, β-D-glucan, as an immunomodulatory adjuvant. The proposed vaccine was developed to effectively coordinate innate and adaptive immunity for potent host defense against viral infection.MethodsWe demonstrated β-D-glucan mediated innate and adaptive immune responses in mice and pigs in vitro and in vivo. The expressions of pattern recognition receptors, cytokines, transcription factors, and co-stimulatory molecules were promoted via FMD vaccine containing β-D-glucan.Resultsβ-D-glucan elicited a robust cellular immune response and early, mid-, and long-term immunity. Moreover, it exhibited potent host defense by modulating host’s innate and adaptive immunity.ConclusionOur study provides a promising approach to overcoming the limitations of conventional FMD vaccines. Based on the proposed vaccine’s safety and efficacy, it represents a breakthrough among next-generation FMD vaccines

Detection of Single Nanoparticles inside a Single Terahertz Resonator

With the rapid advancement of 5G/6G communications using millimeter wavelengths, the concomitant usage of these long wavelength radiation for remote sensing and monitoring of biological and chemical agents is anticipated. However, the ability to detect and identify these agents with sizes ranging from nanometers to microns is hampered by its millimeter wavelength, which drastically reduces the interaction cross-section. Herein, it is reported that single gold nanoparticles (NPs) drop-casted on the nanoresonator can be observed by monitoring the far-field transmitting spectra of individual terahertz (THz) nanoresonators, which enhance the electric field hundreds of times on the nanoscale. Despite the enormous mismatch in length scales, full-wave 3D numerical modeling of the single THz nanoresonator is also performed to interpret the experimental results, indicating the possibility to turn off the resonance using only one NP embedded in the hotspot of the nanoresonator. Such NP detection becomes the most sensitive when the particle, whose size is comparable to the gap width, is tightly fitted into the nanoresonator. This work unveils the potential associated with refractive index sensing and hyperspectral absorption spectroscopy for detecting and fingerprinting ultra-low density of bio/chemical molecules such as viruses, lipid vesicles, and explosives

D-galacto-D-mannan-mediated Dectin-2 activation orchestrates potent cellular and humoral immunity as a viral vaccine adjuvant

IntroductionConventional foot-and-mouth disease (FMD) vaccines have been developed to enhance their effectiveness; however, several drawbacks remain, such as slow induction of antibody titers, short-lived immune response, and local side effects at the vaccination site. Therefore, we created a novel FMD vaccine that simultaneously induces cellular and humoral immune responses using the Dectin-2 agonist, D-galacto-D-mannan, as an adjuvant.MethodsWe evaluated the innate and adaptive (cellular and humoral) immune responses elicited by the novel FMD vaccine and elucidated the signaling pathway involved both in vitro and in vivo using mice and pigs, as well as immune cells derived from these animals.ResultsD-galacto-D-mannan elicited early, mid-, and long-term immunity via simultaneous induction of cellular and humoral immune responses by promoting the expression of immunoregulatory molecules. D-galacto-D-mannan also enhanced the immune response and coordinated vaccine-mediated immune response by suppressing genes associated with excessive inflammatory responses, such as nuclear factor kappa B, via Sirtuin 1 expression.ConclusionOur findings elucidated the immunological mechanisms induced by D-galacto-D-mannan, suggesting a background for the robust cellular and humoral immune responses induced by FMD vaccines containing D-galacto-D-mannan. Our study will help to facilitate the improvement of conventional FMD vaccines and the design of next-generation FMD vaccines

Guidelines for Tailored Chemical Functionalization of Graphene

Graphene oxide (GO) has been synthesized by the Hummers method with modification of experimental condition by different research groups, but there is no guideline to prepare tailored GO for targeted applications. In this research, we suggest a guideline for tailor-fittable functionalization of graphene on the basis of the scope of our previous report on the two-step oxidation of GO. We describe a detailed procedure for synthesis of GO, effects of degree of step I oxidation on characteristics of GO and comparing them with effects of degree of step II oxidation. Characteristic changes of GO occurring during step I oxidation and those occurring during step II oxidation are different in species of oxygen functional groups, interlayer spacing, thermal stability, size distribution, and yield of GO. On the basis of the results, three types of tailor-fitted GO for a fiber, transparent conducting film, and hydrogen storage material are synthesized by controlling the degree of step I and step II oxidation. Compared to the reference GO synthesized by conventional modified Hummers method, the tailor-fitted GO showed 33.5%, 117%, and 104% enhanced performance in strength of the fiber, figure of merits of transparent conducting film, and hydrogen storage, respectively. Our results show that the performance of GO based application is significantly influenced by the synthesis condition of GO, and optimized performance of the applications can be obtained by the tailor-fitted functionalization of GO. We anticipate that this study would be helpful for a variety of researches, both synthesis and application of GO