Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.

The goal of this study was to examine whether supplemental fructooligosaccharides (FOS) and (or) mannanoligosaccharides (MOS) influenced indices of gut health of dogs. Adult female dogs (n = 4) surgically fitted with ileal cannulas were fed a dry, extruded, kibble diet twice daily. At each feeding, the following treatments were administered: 1) Control (no FOS or MOS); 2) 1 g FOS; 3) 1 g MOS; or 4) 1 g FOS + 1 g MOS. Fecal, ileal and blood samples were collected during the last 4 d of each 14-d period to measure protein catabolite concentrations, microbial populations, immune characteristics and nutrient digestibilities. Treatment means were compared using preplanned orthogonal contrasts. Dogs supplemented with MOS had lower (P = 0.05) fecal total aerobes and tended to have greater (P = 0.13) Lactobacillus populations. Ileal immunoglobulin (Ig) A concentrations were greater (P = 0.05) in dogs supplemented with FOS + MOS vs. control. Lymphocytes (% of total white blood cells) were greater (P < 0.05) in dogs supplemented with MOS. Serum IgA concentrations also tended (P = 0.13) to be greater in dogs supplemented with MOS. Dogs supplemented with FOS and FOS + MOS had lower (P < 0.05) fecal total indole and phenol concentrations. Dogs supplemented with MOS tended to have lower ileal DM (P = 0.149) and OM (P = 0.146) digestibilities vs. control. Results of this study suggest that dietary supplementation of FOS and MOS may have beneficial effects on colonic health and immune status of dogs.

Live attenuated vaccines are generally highly efficacious and often superior to inactivated vaccines, yet the underlying mechanisms of this remain largely unclear. Here we identify recognition of microbial viability as a potent stimulus for follicular helper T cell (T cell) differentiation and vaccine responses. Antigen-presenting cells (APCs) distinguished viable bacteria from dead bacteria through Toll-like receptor 8 (TLR8)-dependent detection of bacterial RNA. In contrast to dead bacteria and other TLR ligands, live bacteria, bacterial RNA and synthetic TLR8 agonists induced a specific cytokine profile in human and porcine APCs, thereby promoting T cell differentiation. In domestic pigs, immunization with a live bacterial vaccine induced robust T cell and antibody responses, but immunization with its heat-killed counterpart did not. Finally, a hypermorphic TLR8 polymorphism was associated with protective immunity elicited by vaccination with bacillus Calmette-Guérin (BCG) in a human cohort. We have thus identified TLR8 as an important driver of T cell differentiation and a promising target for T cell-skewing vaccine adjuvants.

Fructooligosaccharides (FOS) are naturally occurring sugars with potentially beneficial nutritional effects. They are widely distributed throughout the plant kingdom. An ion chromatographic method was developed to rapidly and accurately measure FOS in selected food and feed ingredients ingested by humans and animals. The objective of this study was to determine the 1-kestose (1-kestotriose; GF 2 ), nystose (1,1-kestotetraose; GF 3 ), and 1 F --fructofuranosylnystose (1,1,1-kestopentaose; GF 4 ) content of a wide variety of foods and feedstuffs. After extraction with water and appropriate filtration, samples were chromatographed, using an alkaline sodium acetate gradient, through an ion exchange column and guard fitted to a Dionex chromatography unit equipped with a pulsed electrochemical detector. All samples were prepared both with and without spikes of standards to verify recovery and peak identification. Samples of the Compositae family were highest in total FOS followed by Allium species of the Amaryllidadeae family. The method provided excellent separation, recovery, and quantification of the GF n units of FOS. Accurate quantitation of FOS will allow more precise nutritional formulations to be developed with respect to inclusion of this functional food component in human and animal diets.