Pre-clinical development of a vaccine against Lassa fever.

Lassa virus (LASV) is a persistent global health threat that causes about half a million cases of Lassa fever each year in Western Africa. Although most cases are mild, the disease can cause significant morbidity and results in as many as 5,000 deaths per year. Since 2015, Nigeria has been experiencing a severe and extended outbreak of Lassa fever, raising concerns that it could spill over into other countries and reach a magnitude similar to the West African Ebola outbreak of 2013-2016. Despite the burden that Lassa fever places on public health, both in Africa and around the world, there are still no clinically-approved therapeutics or vaccines to treat or prevent it. Nevertheless, a number of promising candidate vaccines have been developed over the last several years, and there is a growing political and social determination to drive at least one of these candidates towards licensure. This paper describes a LASV vaccine candidate that is being developed at Canada's National Microbiology Laboratory. Based on the same live attenuated vesicular stomatitis virus (VSV) vaccine platform that was used to produce the successful Ebola virus vaccine, the VSV-based LASV vaccine has been shown to elicit a potent and protective immune response against LASV. The vaccine shows 100% protection in the "gold-standard" nonhuman primate model of Lassa fever, inducing both humoral and cellular immune responses. Moreover, studies have shown that a single vaccination may offer universal protection against numerous different strains of the virus, and additional studies have shown that immunization with the VSV platform appears to be unaffected by pre-existing immunity to VSV. The next step in the development of the VSV-based LASV vaccine is phase I human clinical trials to assess vaccine safety and dosage.

Supplementation of monensin and Optimase to beef cows consuming low-quality forage during late gestation and early lactation.

Two experiments were designed to investigate the effects of feeding monensin and/or slow release urea with a fibrolytic feed enzyme (Optimase; Alltech, Inc., Nicholasville, KY) on performance, milk production, calf growth performance, and blood metabolites in beef cows. Spring-calving cows and heifers were used in a completely randomized design in Exp. 1 (N = 84; 534 ± 68 kg initial BW) and Exp. 2 (N = 107; 508 ± 72 kg initial BW). Exp. 1 supplements were formulated to meet cow protein requirements and fed daily and included 1) cottonseed meal with no monensin (control); or 2) monensin added to control to supply 200 mg per head per d (MON). In Exp. 2, experimental supplements included 1) cottonseed meal/wheat middlings (CS) fed at a rate to provide adequate DIP and CP according to , 2) the CS plus soybean hulls and 61 g per cow per d Optimase (OPT), 3) the CS plus monensin to supply 200 mg per cow per d (MON2), and 4) OPT plus MON2 (Combo). Cows were fed in last trimester through early lactation in Exp. 1 and during 2nd trimester in Exp. 2. Data were analyzed using the Mixed procedure in SAS with animal as the experimental unit. In Exp. 1, treatment did not affect cow BW or BCS change (P > 0.19). Calf birth BW was not affected by dam treatment (P = 0.24); however, calves from dams consuming MON weighed more (P < 0.04) at d 45 and at trial end. Calves also had greater (P = 0.04) ADG from birth to trial end. Milk production did not significantly differ among treatments (P > 0.41). In Exp. 2, mean cow BW and BCS were similar (P > 0.35) among treatments on d 90. However, from d 0 to 54, cows assigned to the OPT supplement gained less BCS (P = 0.02) compared with cows assigned to the CS supplement. Cumulative BCS gain was greater (P < 0.01) for CS-fed cows than for cows fed the OPT and MON2 supplements, although it was not significantly different for cows fed the Combo supplement. These studies indicate that the influence of monensin on cow BW and BCS change is inconsistent. The potential for monensin supplementation to positively impact calf performance during early lactation seems to be clearer. Replacing a portion of oilseed N in the supplement with Optimase may marginally reduce cow performance. Further research is needed to determine both the effects of monensin and the implications of combining monensin with Optimase on forage intake and cow performance at various stages of production.

Effects of starch- vs. fiber-based energy supplements during winter grazing on partitioning of fat among depots and adipose tissue gene expression in growing cattle and final carcass characteristics.

Fifty-five normal-weaned Angus steers (268 ± 22 kg; 265 ± 16 d of age) were used to evaluate the effects of starch- vs. fiber-based energy supplements for stocker cattle grazing low-quality dormant native range on growth performance, body composition, and adipose tissue development of different fat depots. Steers were randomly allotted to 4 treatments: 1.02 kg·steer(-1)·d(-1) of a 40% CP cottonseed meal-based supplement (CON), corn/soybean meal-based supplement fed at 1% of BW (CORN), soybean hull/soybean meal-based supplement fed at 1% of BW (SBH), or dried distillers grains with solubles fed at 1% of BW (DDGS). All supplements were individually fed 5 d/wk during the 121-d winter grazing phase. After winter grazing, 3 steers per treatment were harvested to determine body composition and carcass characteristics, and collect subcutaneous (SC) and perirenal (PR) adipose tissue samples. The remaining steers grazed cool-season grass pastures for 74 d without supplementation before finishing. Steers were fed a common finishing diet for 113 d before harvest, at which time carcass characteristics were collected at a commercial abattoir. Energy supplementation increased (P < 0.01) winter grazing ADG compared with CON steers, and CORN steers had greater (P < 0.01) ADG than SBH and DDGS steers. Energy supplementation increased (P < 0.04) mesenteric/omental fat mass but did not influence (P > 0.13) 12th rib fat thickness or marbling score at intermediate harvest compared with CON steers. The mRNA expression of genes involved in lipogenesis and markers of adipogenesis were greater (P < 0.05) in PR adipose tissue of energy-supplemented steers compared with CON steers but not in SC adipose tissue. Fiber-supplemented steers had greater (P < 0.01) mRNA expression of fatty acid synthase and fatty acid binding protein 4 compared with CORN steers in PR adipose tissue but not SC adipose tissue. At final harvest, energy-supplemented steers had greater (P < 0.05) KPH and yield grade than CON steers, but no differences (P = 0.75) in marbling score were observed. Neither energy supplementation nor type of energy supplement influenced intramuscular fat deposition in stocker cattle grazing dormant native range. These data suggest that the total energy intake and stage of animal maturity during grazing supplementation were not great enough to influence marbling deposition.

Effect of extended withdrawal of zilpaterol hydrochloride on performance and carcass traits in finishing beef steers.

The objective was to evaluate the effects of an extended withdrawal period after feeding the beta-adrenergic agonist zilpaterol hydrochloride (ZH) for 20 d at the end of the feeding period. Three hundred eighty-four crossbred beef steers were blocked by BW and randomly allocated into 64 pens (6 steers/pen). Pens were assigned to treatments in a 2 x 4 factorial arrangement in a randomized complete block design. Main effects were the addition of 0 (control) or 8.3 mg/kg of ZH (DM basis) to the finishing diet for 20 d before estimated average slaughter date and paired withdrawal periods of 3, 10, 17, or 24 d before slaughter. Individual BW were measured initially, 1 d before ZH feeding, and 1 d before slaughter. The ZH feeding period was initiated so that control cattle in the 3-d withdrawal group would be expected to average 65% USDA Choice Quality grade and have 1.27 cm of 12th-rib fat based on visual appraisal. Carcass data were collected at slaughter. For the 3-d withdrawal steers, 2 steers from each pen were selected to determine visceral organ and total offal mass at slaughter. The ZH x withdrawal day interaction was not significant (P > 0.10) for the majority of variables. There was no difference (P > or = 0.12) due to ZH feeding for final BW, carcass-adjusted final BW, or ADG. However, DMI was decreased (P = 0.02) and G:F increased (P = 0.01) in steers fed ZH vs. control steers. As day after withdrawal of ZH increased, there was a linear increase (P < 0.001) in final BW and carcass-adjusted final BW, but a linear decrease (P < 0.001) in ADG over the finishing period and over the ZH plus withdrawal period. Overall, HCW was 380 and 369 kg (P < 0.001) for ZH and control steers, respectively. However, the difference between ZH and control was 14, 17, 5, and 6 kg with 3, 10, 17, and 24 d withdrawal, respectively (ZH x withdrawal day, P = 0.09). Feeding ZH increased dressing percentage (65.8 vs. 64.6%; P < 0.001) and LM area (94.8 vs. 89.7 cm(2); P < 0.001), and decreased calculated yield grade (2.69 vs. 2.91; P = 0.03) and percentage of cattle grading USDA Choice (31.1 vs. 42.3%; P = 0.03) compared with controls. Small intestinal mass (g/kg of empty BW) was greater (P = 0.03) for steers fed ZH compared with controls. There were no other differences (P > or = 0.11) in mass of body components, expressed in kilograms or as a fraction of empty BW. In this experiment, improvements in animal performance and HCW due to feeding ZH were generally maintained when withdrawal was extended through 10 d.

Effects of feeding yeast and propionibacteria to dairy cows on milk yield and components, and reproduction*.

To determine the effect of supplemental feeding of Diamond V-XP yeast (XPY) alone or in combination with propionibacteria strain P169 on milk production, milk components, body weight, days to first and second ovulation, plasma insulin, and plasma and milk glucose, 31 primiparous and multiparous (MP) Holstein cows were fed one of three dietary treatments between 2 weeks prepartum to 30 weeks postpartum: (i) control (n = 10), fed a corn silage-based total mixed ration (TMR); (ii) XPY (n = 11), fed control TMR plus XPY (at 56 g/head/day); and (iii) P169+XPY (n = 10), received control TMR plus XPY plus P169 (at 6 x 10(11) cfu/head/day). After parturition, daily milk weights were recorded, and milk samples were collected twice weekly for milk component analyses. Daily uncorrected milk, solids-corrected milk, and 4% fat-corrected milk production for MP cows fed P169+XPY was 9-16% greater than control MP cows, but these increases were only evident during mid lactation (9-30 weeks). The percentage of milk fat was 8-18% greater in control than XPY and P169+XPY groups. Milk lactose percentage in MP cows fed P169+XPY was 3-5% greater than in control and XPY MP cows. Primiparous and MP cows fed P169+XPY had 28-32% greater milk glucose levels than control and XPY-fed cows. Diurnal plasma glucose concentration was not affected by diet in MP cows. Plasma insulin levels in MP cows fed P169+XPY were 30-34% greater than in other groups of MP cows. Milk glucose and plasma insulin responses to P169+XPY feeding suggest that P169+XPY might have enhanced gluconeogenesis and increased glucose uptake by the mammary gland in Holstein cows. Thus, a combined feed supplement of P169 and XPY may hold potential as a natural feed alternative to hormones and antibiotics to enhance lactational performance.

Effects of feeding propionibacteria to dairy cows on milk yield, milk components, and reproduction.

Two weeks before parturition, 38 Holstein primiparous and multiparous cows were assigned to 1 of 3 treatment groups: control animals (n = 13) received regular total mixed rations (TMR), the low-dose group (n = 14) received the control TMR plus 6 x 10(10) cfu/cow of Propionibacterium strain P169 (P169), and the high-dose group (n = 11) received the control TMR plus 6 x 10(11) cfu/cow of P169 from -2 to 30 wk postpartum. Weekly milk samples were analyzed for percentage of milk fat, protein, lactose, and SNF, milk urea nitrogen, and somatic cell counts. Daily milk production expressed as 4% fat-corrected milk was affected by treatment and week x parity. High-dose and low-dose P169-treated cows exhibited 7.1 and 8.5% increases above controls in daily 4% fat-corrected milk, respectively. Treatment x parity and week significantly influenced percentage of milk fat, lactose, and protein, whereas treatment x parity and treatment x week influenced SNF. Ruminal propionate levels were influenced by treatment such that high-dose P169 cows had greater molar percentage of propionate than did low-dose P169 and control cows. Change in body weight postpartum was influenced by week x parity and treatment x parity such that high-dose and low-dose P169 multiparous cows exhibited a more rapid recovery of wk-1 body weight than did control multiparous cows. There was no treatment, parity, or interaction on days to first postpartum ovulation or on estrous behavior at 45 and 90 d postpartum. We concluded that P169 might have potential as an effective direct-fed microorganism to increase milk production in dairy cows.

Endocrine disruption of uterine insulin-like growth factor expression in the pregnant gilt.

Early exposure of pregnant gilts to oestrogen, prior to the normal period of porcine conceptus oestrogen secretion, disrupts the uterine environment resulting in complete embryonic mortality during the period of placental attachment to the uterine surface. The current study evaluates the uterine insulin-like growth factor (IGF) system following endocrine disruption of early pregnancy in gilts through exposure to exogenous oestrogen on Days 9 and 10 of gestation. Endometrial IGF gene and protein expression, IGF-I receptor (IGF-IR) gene expression, and uterine lumenal content of IGF binding proteins (IGFBPs) were evaluated in control and oestrogen-treated gilts on Days 10, 12, 13, 15 and 17 of gestation. Oestrogen treatment altered endometrial IGF-I and IGF-IR gene expression on Days 12 and 13 of gestation. Uterine content of IGF-I and IGF-II in control gilts was greatest on Days 10, 12, and 13 followed by a four- to sixfold decrease on Day 15 of gestation. Oestrogen treatment caused a premature proteolysis of IGFBPs within the pregnant pig uterus on Day 10 of gestation, and an earlier decline in uterine lumenal IGF-I content. Results demonstrate that early exposure of pregnant gilts to oestrogen causes premature loss of uterine IGFs during the period of conceptus elongation. Timing for the release of uterine IGFs during early porcine conceptus development may play an important function in the ability of the conceptus to attach and survive during the establishment of pregnancy.