Impacts of feeding a Saccharomyces cerevisiae fermentation product on productive performance, and metabolic and immunological responses during a feed-restriction challenge of mid-lactation dairy cows.

Saccharomyces cerevisiae fermentation products are commonly used in dairy cattle ration to improve production efficiency and health. However, whether these benefits will persist during feed-restriction-induced negative energy balance is unknown. The objective of this experiment was to examine the effect of a Saccharomyces cerevisiae fermentation product (NT, NutriTek, Diamond V) on performance, metabolic, inflammatory, and immunological responses to a feed-restriction challenge in mid-lactation dairy cows. Sixty Holstein cows were blocked by parity, days in milk, and milk yield and then randomly assigned to 1 of the 2 supplements: NT or placebo (CTL). The supplements were mixed in total mixed ration before feeding at a rate of 19 g/d per cow. The production phase of the experiment lasted 12 wk. Intake and milk yield were recorded daily, and milk composition was measured weekly. After the production trial, a subset of cows (NT: n = 16; CTL: n = 16) were immediately enrolled in a 5-d feed-restriction challenge with 40% ad libitum intake followed by a 5-d realimentation. Milk yield and composition were measured at each milking from d -2 to 10 relative to feed restriction. Blood samples were collected on d -2, -1, 1, 2, 3, 4, 5, 6, 8, and 10 relative to the initiation of feed restriction to measure circulating metabolites, insulin, cortisol, IL-10, tumor necrosis factor-α, lipopolysaccharide binding protein, and haptoglobin. Immune function assessments, including peripheral mononuclear cell proliferation and functional assays of circulating granulocytes, were performed on d -3 and 4 of the feed restriction. No differences were observed in dry matter intake, milk yield, or concentrations or yield of components except for fat yield. An interaction of parity and treatment was observed for milk fat yield that was lower for CTL than NT in primiparous cows, but no differences were observed among treatments in milk fat yield of multiparous cows. Feed restriction successfully induced negative energy balance and its associated metabolic changes, including reduced concentrations of plasma glucose and increased nonesterified fatty acids and ß-hydroxybutyrate. Cows fed NT had a similar decrease in milk yield but had a more pronounced reduction in plasma glucose concentration and greater ß-hydroxybutyrate concentration during feed restriction than those fed CTL. Feed restriction did not induce evidence of systemic inflammation but did reduce granulocyte functional activity. Compared with CTL, feeding NT improved the reactive oxygen species production by granulocytes after stimulation by extracellular antigens. In conclusion, feeding NT increased milk fat production of first-lactation cows but did not affect overall productive performance. However, supplementation with NT improved induced granulocyte oxidative burst. This may explain the greater glucose utilization by cows fed NT rather than CTL during feed restriction.

Ocular exposure to infectious laryngotracheitis virus alters leukocyte subsets in the head-associated lymphoid tissues and trachea of 6-week-old White Leghorn chickens.

Infectious laryngotracheitis virus (ILTV), an alphaherpesvirus, causes acute respiratory disease primarily infecting the upper respiratory tract and conjunctiva. Administration of live attenuated ILTV vaccines via eye drop, drinking water, or by coarse spray elicits protective mucosal immunity in the head-associated lymphoid tissues (HALT), of which conjunctiva-associated lymphoid tissue (CALT) and the Harderian gland (HG) are important tissue components. The trachea, a non-lymphoid tissue, also receives significant influx of inflammatory cells that dictate the outcome of ILTV infection. The objective of this study was to evaluate leukocyte cellular and phenotypic changes in the CALT, HG and trachea following ocular infection with a virulent ILTV strain. At 1, 3, 5, 7 and 9 days post-infection, CALT, HG, and trachea of 6-week-old specific pathogen free (SPF) chickens ocularly-exposed to vehicle or virulent ILTV strain 63140 were dissociated, the cells enumerated and then phenotyped using flow cytometry. The CALT had the highest viral genomic load, which peaked on day 3. In ILTV-infected birds, the CALT had a decreased percentage of leukocytes. This was reflected by decreased numbers of MHCI+MHCII-, MHCI+MHCIIlow+, and CD4+ cells, while IgM+ and MHCI+MHCIIHigh+ expressing cell populations increased. In the HG, the most notable change in cells from ILTV-infected birds was a decrease in IgM expressing cells and histologically, an increase in Mott cells. In summary, an acute, ocular exposure to ILTV strain 63140 in young birds shifts subsets of lymphocyte populations in the CALT and HG with minimal impact on the trachea.

Lead alters intracellular protein signaling and suppresses pro-inflammatory activation in TLR4 and IFNR-stimulated murine RAW 264.7 cells, in vitro.

Lead (Pb) is a persistent environmental pollutant that has a structure and charge similar to many ions, such as calcium, that are essential for normal cellular function. Pb may compete with calcium for protein binding sites and inhibit signaling pathways within the cell affecting many organ systems including the immune system. The aim of the current study was to assess whether the calcium/calmodulin pathway is a principal target of environmentally relevant Pb during pro-inflammatory activation in a RAW 264.7 macrophage cell line. RAW 264.7 cells were cultured with 5 µM Pb(NO3)2, LPS, rIFNγ, or LPS+rIFNγ for 12, 24, or 48 hr. Intracellular protein signaling and multiple functional endpoints were investigated to determine Pb-mediated effects on macrophage function. Western blot analysis revealed that Pb initially modulated nuclear localization of NFκB p65 and cytoplasmic phosphorylation of CaMKIV accompanied by increased phosphorylation of STAT1ß at 24 hr. Macrophage proliferation was significantly decreased at 12 hr in the presence of Pb, while nitric oxide (NO) was significantly reduced at 12 and 24 hr. Cells cultured with Pb for 12, 24, or 48 hr exhibited altered cytokine levels after specific stimuli activation. Our findings are in agreement with previous reports suggesting that macrophage pro-inflammatory responses are significantly modulated by Pb. Further, Pb-induced phosphorylation of CaMKIV (pCaMKIV), observed in the present study, may be a contributing factor in metal-induced autophagy noted in our previous study with this same cell line.

Isolation and characterisation of a novel trophoblast side-population from first trimester placentae.

The placenta is responsible for all nutrient and gas exchange between mother and baby during pregnancy. The differentiation of specialised placental epithelial cells called trophoblasts is essential for placental function, but we understand little about how these populations arise. Mouse trophoblast stem cells have allowed us to understand many of the factors that regulate murine trophoblast lineage development, but the human placenta is anatomically very different from the mouse, and it is imperative to isolate a human trophoblast stem cell to understand human placental development. Here we have developed a novel methodology to isolate a Hoechst side-population of trophoblasts from early gestation placentae and compared their transcriptome to differentiated trophoblast populations (cytotrophoblasts and extravillous trophoblasts) using microarray technology. Side-population trophoblasts clustered as a transcriptomically distinct population but were more closely related to cytotrophoblasts than extravillous trophoblasts. Side-population trophoblasts up-regulated a number of genes characteristic of trophectoderm and murine trophoblast stem cells in comparison to cytotrophoblasts or extravillous trophoblasts and could be distinguished from both of these more mature populations by a unique set of 22 up-regulated genes, which were enriched for morphogenesis and organ development and the regulation of growth functions. Cells expressing two of these genes (LAMA2 and COL6A3) were distributed throughout the cytotrophoblast layer at the trophoblast/mesenchymal interface. Comparisons to previously published trophoblast progenitor populations suggest that the side-population trophoblasts isolated in this work are a novel human trophoblast population. Future work will determine whether these cells exhibit functional progenitor/stem cell attributes.

Origins and environmental mobility of antibiotic resistance genes, virulence factors and bacteria in a tidal creek's watershed.

AIMS: To compare bacterial compositions of watershed run-offs released by a human settlement and a forested area, and to evaluate their role as carriers of antibiotic resistance and virulence genes. METHODS AND RESULTS: Run-offs from a forested area and a small settlement in a tidal creek' s watershed were compared for bacterial composition and profiles of 16 tetracycline resistance (TRG), eight virulence (VG) and integrase1 and 2 genes. Integrase 1 gene was detected only once. No integrase 2 gene was observed. VGs were detected only in settlement's run-offs, and TRG incidence frequency there was twice as high as in the forest's run-offs. Gene incidences revealed a positive correspondence to the rainfall, and weak correlations to water parameters. Metagenomic, Principle Coordinates and Shannon analyses together revealed distinctive bacterial compositions of the forest's and settlement's run-offs. Passage of the latter through a salt marsh resulted in the elimination of TRGs and three-fold decrease in VG incidence, and their bacterial composition was shifted towards that of the tidal creek. CONCLUSIONS: The settlement was a major source of TRGs and VGs in the watershed, but these contaminants were mitigated by a salt marsh system. SIGNIFICANCE AND IMPACT OF THE STUDY: Our data revealed the role of small settlements in biological contamination of the coastal waters. They also indicated that salt marshes are capable of reducing not only chemical but also biological contamination of run-offs.

Technical note: Development of a challenge model for Streptococcus uberis mastitis in dairy heifers.

A challenge model for experimentally inducing Streptococcus uberis mastitis in bred dairy heifers was developed. Qualifying heifers (n=7) exhibited antibody titers of <1:10,000 against Strep. uberis antigens and were free of intramammary infections (IMI). Two contralateral quarters of each heifer were assigned to receive an infusion of Strep. uberis (1,000 to 2,000 cfu); remaining quarters served as unchallenged controls. For a successful challenge and infection, 3 of 4 consecutive mammary secretion samples had to culture positive for Strep. uberis. Six of the 7 heifers were challenged successfully in both infused quarters with a mean dose of 1,080 cfu; once confirmed, infections were treated with a one-time infusion of nonlactating cow therapy. Before challenge, mammary secretion leukocyte counts averaged 8.4×10(6)/mL in all quarters. At 24h after challenge, leukocyte count increased to 18.4×10(6)/mL in challenged quarters, peaking on d 5 at 24.3×10(6)/mL; unchallenged quarters remained at ≤10.4×10(6)/mL, but increased to 15.2×10(6)/mL on d 7 and then decreased. Before challenge, macrophages predominated (81%) in mammary secretions followed by lymphocytes (15.3%) and neutrophils (3.7%). By 24h after challenge, neutrophils increased in challenged quarters and predominated for the duration of the trial (65.3 to 70%), whereas macrophages predominated in unchallenged control quarters (65.2 to 75.2%). The challenge model was successful in establishing Strep. uberis IMI in 85.7% of animals, and IMI were controlled (100% cure) by administering nonlactating cow therapy. All heifers calved free of IMI and antimicrobial residues, with milk production similar to that of herd mates and with somatic cell counts (SCC) <200,000 cells/mL.

Changes in serum testosterone and anti-Müllerian hormone concentration in bulls undergoing scrotal insulation.

While changes in semen quality after heat stress are well characterized in the bull, changes in endocrine function have not been critically evaluated. It was hypothesized here that scrotal insulation results in alterations in Sertoli cell and Leydig cell function, as measured by changes in serum testosterone and anti-Müllerian hormone (AMH) concentration. Scrotal insulation bags were placed in 10 bulls for 8 d. Blood was collected on days -22 and -2, and weekly from days 5 to 96 (day 0 = first day of scrotal insulation) for measurement of serum concentration of AMH and testosterone using ELISA. The concentration of AMH decreased on day 5, followed by an increase on day 54 (P = 0.014). When AMH concentration was normalized to pre-insulation values, the percent increase in serum concentration of AMH was significant between days 26 and 54, with another peak at 75 d (P = 0.031). The serum concentration of testosterone (P = 0.0001) and the percentage of change in testosterone concentration (P < 0.0001) increased on day 5, followed by a decrease from days 33 to 96. Scrotal insulation was associated with Sertoli and Leydig cell dysfunction, as measured by serum testosterone and AMH concentration. The persistently low concentration of testosterone at the end of the study suggests a long term effect of scrotal insulation on Leydig cell function.

Exogenic origin for the volatiles sampled by the Lunar CRater Observation and Sensing Satellite impact.

Returning humans to the Moon presents an unprecedented opportunity to determine the origin of volatiles stored in the permanently shaded regions (PSRs), which trace the history of lunar volcanic activity, solar wind surface chemistry, and volatile delivery to the Earth and Moon through impacts of comets, asteroids, and micrometeoroids. So far, the source of the volatiles sampled by the Lunar Crater Observation and Sensing Satellite (LCROSS) plume has remained undetermined. We show here that the source could not be volcanic outgassing and the composition is best explained by cometary impacts. Ruling out a volcanic source means that volatiles in the top 1-3 meters of the Cabeus PSR regolith may be younger than the latest volcanic outgassing event (~1 billion years ago; Gya).

Viscoelastic property mapping with contact resonance force microscopy.

We demonstrate the accurate nanoscale mapping of near-surface loss and storage moduli on a polystyrene-polypropylene blend with contact resonance force microscopy (CR-FM). These viscoelastic properties are extracted from spatially resolved maps of the contact resonance frequency and quality factor of the AFM cantilever. We consider two methods of data acquisition: (i) discrete stepping between mapping points and (ii) continuous scanning. For point mapping and low-speed scanning, the values of the relative loss and storage modulus are in good agreement with the time-temperature superposition of low-frequency dynamic mechanical analysis measurements to the high frequencies probed by CR-FM.

The relationship between physical activity and low back pain outcomes: a systematic review of observational studies.

Although clinical guidelines advocate exercise and activity in the management of non-specific low back pain (NSLBP), the link between levels of physical activity and outcomes is unclear. This systematic review investigated the relationships between free living activity levels after onset of low back pain (LBP) and measures of pain, and disability in patients with NSLBP. Cohort and cross-sectional studies were located using OVID, CINAHL, Medline, AMED, Embase, Biomed, PubMed-National Library of Medicine, Proquest and Cochrane Databases, and hand searches of reference lists. Studies were included if a statistical relationship was investigated between measures of free living physical activity (PA) in subjects with LBP and LBP outcome measures. Twelve studies (seven cohort and five cross-sectional) were included. One prospective study reported a statistically significant relationship between increased leisure time activity and improved LBP outcomes, and one cross-sectional study found that lower levels of sporting activity were associated with higher levels of pain and disability. All other studies (n = 10) found no relationship between measures of activity levels and either pain or disability. Heterogeneity of study designs, particularly in terms of activity measurement, made comparisons between studies difficult. These data suggest that the activity levels of patients with NSLBP are neither associated with, nor predictive of, disability or pain levels. Validated activity measurement in prospective research is required to better evaluate the relationships between PA and LBP.

Laser-assisted vitrification of large equine embryos.

The major difficulty in providing the benefits of embryo cryopreservation for equine agriculture is the mismatch between the optimal embryo age for collection from the mare (7-8 days after ovulation was detected) and the optimal age for freezing under current methods (6.5 days after ovulation). To overcome this limitation, we tested a method to enhance penetration of cryopreservative across the capsule and trophoblast of day 7 and 8 embryos combined with rapid freezing by vitrification. Six small embryos (<300 µm in diameter) were collected on day 6-7 after ovulation and twelve larger embryos were recovered on day 7-8. In the treatment group, replacement of blastocoelic fluid with cryopreservative solution was facilitated by a laser system used to create a small opening in the embryonic capsule and trophectoderm. All embryos were vitrified using a CryoLeaf freezing support. After recovery from freezing and embryo transfer, three of four small untreated embryos (<300 µm in diameter, 75%) and four of nine large blastocysts in the treatment group (>300 µm in diameter, 44%) resulted in a vesicle as detected by ultrasonography approximately one week after transfer. However, only one recipient mare was still pregnant on day 23, and she delivered a live foal. Further investigation is required to determine why most of the embryos in this experiment were lost between day 13 and day 23 of gestation.

Differences in antimicrobial susceptibility testing complicating management of IMP carbapenemase-producing Enterobacterales infection.

OBJECTIVES: IMP-type carbapenemases are rarely detected in Europe and limited information is available to guide the treatment of infections caused by carbapenemase-producing Enterobacterales (CPE) producing these carbapenemases. Accurate antimicrobial susceptibility testing (AST) results are essential for optimal antibiotic management. Here we report discrepancies in AST of IMP-producing Enterobacterales (IMP-CPE) complicating the management of severe sepsis. METHODS: Antimicrobial susceptibilities were analysed by in-house VITEK® 2, Etest and broth microdilution (BMD). Carbapenemase-encoding genes were detected by PCR. Whole-genome sequencing (WGS) was performed using an Illumina MiSeq platform. RESULTS: Minimum inhibitory concentrations (MICs) determined by VITEK® 2 for Enterobacter hormaechei and Klebsiella oxytoca blood culture isolates were ≥16 mg/L for meropenem and ≤0.5 mg/L for ertapenem. In contrast, Etest analysis and BMD returned MICs of 2 mg/L and 1 mg/L, respectively. Both isolates tested positive for IMP carbapenemase-encoding genes by PCR. WGS revealed that both isolates carried the same blaIMP-4 gene. Based on VITEK® 2 susceptibilities, initial treatment was with tigecycline and amikacin. After subsequent deterioration, the patient was successfully treated with ertapenem and amikacin. CONCLUSION: This case highlights that automated AST by VITEK® 2 can over-report meropenem resistance for IMP carbapenemase-producers compared with Etest and BMD. Clinicians need to be cautious deciding against carbapenem treatment based on VITEK® 2 susceptibility testing results for IMP-positive Enterobacterales. Tigecycline was inferior to carbapenem treatment for pyelonephritis caused by isolates expressing IMP carbapenemases, however specific evidence guiding the treatment of these infections is lacking.

Sperm-bound antisperm antibodies are associated with poor cryosurvival of stallion spermatozoa.

Different stallions exhibit a high level of variation in the ability of their sperm to survive cryopreservation. A large fraction of stallions show poor post-thaw sperm motility, and their semen is not suitable for commercial freezing. In this study, we hypothesized that the presence of sperm-bound antisperm antibodies (ASAs) was associated with poor cryosurvival of stallion sperm. Our objective was to assess the level of ASA binding to stallion sperm, and determine if it was associated with good or poor sperm cryosurvival. In Experiment 1, cooled shipped semen from 27 stallions was frozen using three commercial semen extenders. Sperm motility, membrane integrity, acrosome integrity and apoptosis were evaluated before and after freezing for each aliquot. In addition, the percentage of ASA-bound sperm was evaluated post-thaw. In Experiment 2, semen from 22 stallions was frozen immediately after collection a single formulation of semen extender. Sperm motility and ASA binding were evaluated post-thaw. The results of both experiments showed similar findings. The frequency of ASA-positive samples was higher among stallions with poor sperm cryosurvival (Exp. 1 and 2 = 6/11, 54.5%) than for good sperm cryosurvival (Exp. 1 = 0/16, 0%; Exp. 2 = 1/11, 9.1%). The percentage of IgG- and IgA-bound sperm was also higher in stallions with poor sperm cryosurvival in both experiments (P < 0.05). Post-thaw sperm motility, velocity and distance parameters were lower in ASA-positive than ASA-negative stallions (P < 0.005). No effect of the semen extender used was observed. In addition, stallions with ASAs had a higher percentage of apoptotic sperm than stallions without ASAs. The presence of sperm-bound ASAs was associated with poor cryosurvival for stallion spermatozoa. Thus, it may be beneficial to evaluate stallions for binding of ASAs prior to freezing to offer and indicator of the prognosis for cryosurvival.

Health status of caregivers of children with cerebral palsy.

BACKGROUND AND AIMS: While a 'Family-Centered' approach to care is accepted as best practice in the context of childhood disability, it may lead to increased demands on family members by requiring them to be active participants in their child's care. This may impact upon the physical and mental health of the caregiver and therefore needs to be investigated. This study aimed to assess the health status of caregivers of children with cerebral palsy (CP) in Ireland and to identify vulnerable subgroups. METHODS: A cross-sectional postal survey was conducted using a questionnaire incorporating the SF-36v2.0. The sample consisted of male and female caregivers of children with CP, representing all levels of ability. Two questionnaires were sent to each child's home; a total of 312 questionnaires were sent to the homes of 156 children. RESULTS: Completed questionnaires were returned by 161 caregivers (100 women, 61 men) of 101 children, giving a response rate of 65%. Caregivers of children with CP were found to have poorer health than the Irish general population, for whom normative data exist. Female caregivers had poorer health than male caregivers in both the physical (P < 0.05) and mental health (P < 0.001) domains of the SF-36. Caregivers spending more time caring had significantly poorer mental health than those spending less time caring (P < 0.05). There was no difference in the health of caregivers of 'more independent' versus 'more dependent' children, apart from the latter group reporting higher levels of bodily pain (P < 0.05). CONCLUSION: This study provides evidence of the inferior health status of caregivers of children with CP in Ireland, particularly that of women.

Optimization of cryopreservation protocols for cooled-transported stallion semen.

Freezing cooled-transported semen allows veterinarians and breeders to collect and process the semen of stallions on farm, and then ship the semen to a semen freezing center. There, however, is a lack of standardization of shipping and freezing protocols. The objectives were to optimize and simplify protocols to freeze cooled-shipped semen. In Experiment 1, cooled-transported semen was centrifuged at room temperature or 5 °C before freezing. Sperm variables (motility, membrane integrity, acrosome integrity, membrane fluidity) were evaluated before and after freezing. Centrifugation temperature had no effect on post-thaw semen quality. In Experiment 2, cooled-transported semen was centrifuged at room temperature and cryopreserved in three semen freezing extenders. With use of the improved modified French formula, there was less post-thaw total and progressive motility compared with use of Botucrio or the improved lactose-EDTA formula (P<0.0001). Semen cryopreserved in the improved modified French formula also had a lesser percentage of sperm with intact membranes compared with lactose-EDTA, and a greater percentage of sperm with capacitation-like changes compared with Botucrio (P<0.0001). In Experiment 3, semen diluted in each extender was frozen conventionally or placed directly in a -80 °C ultra-freezer. Freezing in the ultra-freezer resulted in a lesser post-thaw sperm motility, but not membrane and acrosome integrity and capacitation-like changes. In conclusion, centrifugation and addition of freezing extender to cooled transported semen can be performed at room temperature or 5 °C. The Botucrio and lactose-EDTA formula are recommended for conventional cryopreservation of cooled-transported stallion semen as compared with the modified French formula.

Lunar soil hydration constrained by exospheric water liberated by meteoroid impacts.

Analyses of samples from the Apollo missions suggest that the Moon formed devoid of native water. However, recent observations by Cassini, Deep Impact, Lunar Prospector and Chandrayaan-1 indicate the existence of an active water cycle on the Moon. Here we report observations of this water cycle, specifically detections of near-surface water released into the lunar exosphere by the Neutral Mass Spectrometer on the Lunar Atmosphere and Dust Environment Explorer. The timing of 29 water releases is associated with the Moon encountering known meteoroid streams. The intensities of these releases reflect the convoluted effects of the flux, velocity and impact location of the parent streams. We propose that four additional detected water releases represent the signature of previously undiscovered meteoroid streams. We show that water release from meteoroid impacts is indicative of a lunar surface that has a desiccated soil layer of several centimetres on top of uniformly hydrated soil. We infer that the Moon is currently in the process of losing water that was either delivered long ago or present at its formation.

Effects of an immunomodulatory feed additive on intramammary infection prevalence and somatic cell counts in a dairy herd experiencing major health issues.

A trial was conducted to determine if feeding OmniGen-AF® (OG) to 22 late lactation cows 60 days prior to and during the early dry period, a time of increased susceptibility to mastitis, could reduce disease incidence in a dairy herd experiencing major health issues. Treated cows (n = 11) consumed a ration containing OG [9 g/100 kg of body weight/day] beginning 60 days before dry-off, during the dry period, and through 30 days in milk (DIM). Control cows received the same ration during the dry period through 30 DIM only. Body weights, body condition scores (BCS), intramammary infection (IMI) prevalence, new IMI rates, somatic cell counts (SCC), milk yield, and adverse health events were measured. No differences were found between treatments for body weight or BCS. Adverse health event data at calving showed no differences between treatments except for percentage of cows with hyperketonemia, which was lower among treated cows (63.6% vs 100%). Prevalence of IMI from calving through 30 DIM for treated cows (6.1%) was lower than controls (11.05%); likewise, new IMI rate during this time for treated cows (0.61%) was lower than controls (5.81%). The SCC from calving through 30 DIM for treated cows (215,000/ml) was lower than controls (493,000/ml). Average production/day at the first DHIA test (~33 DIM) showed that treated cows produced more milk (39.9 kg) than controls (35.34 kg). In conclusion, feeding OG 60 days prior to dry-off reduced hyperketonemia and mastitis, lowered SCC, and numerically increased milk yield in a dairy herd experiencing major health issues.

An immunomodulatory feed additive enhances in vitro viral vaccine recall antigen responses in dairy heifers.

Enhancing immunological responses to vaccination is an important goal in many herd health management systems. OmniGen-AF®(OG) is an immunomodulatory feed additive that has been shown to enhance innate immune function in ruminants and its effects on adaptive immunity require additional study. The objective of this study was to evaluate post-vaccine antibody titers and circulating cellular memory development in heifers fed OG and administered a commercially available modified-live bovine respiratory disease (BRD) vaccine. Twenty-four Holstein heifers were assigned to one of two diets for 170 days: Control TMR (CON; n = 11), or TMR plus OG (TRT; 9 g/100 kg BW/day; n = 13). Samples for hematology, serology, and cellular assays were collected on D-110, 0, 21, 42, and 60 of the trial. Heifers were administered two priming doses of a modified-live BRD vaccine, with a third dose given on D0. There were no significant differences in total WBC and absolute number or the percentage of circulating lymphocytes, monocytes, neutrophils, RBC, or platelets on D-110 through D21. On D42 and D60, CON had significantly higher numbers of lymphocytes. On D0, mean serum neutralizing (SN) titer to BHV-1 was significantly higher for CON compared to TRT. SN titers were not significantly different between CON and TRT at any other time point for BHV-1, BVDV type 1, or BVDV type 2. TRT mounted a significantly stronger recall proliferative response to 0.5 multiplicity of infection (MOI) of BHV-1, BVDV type 1 and BVDV type 2 on D42 and D60; 0.25 MOI of BVDV type 1 on D21 and D42; and 0.25 MOI BVDV type 2 on D42 compared to CON. IL-4 production induced by 0.5 and 1.0 MOI BHV-1 (D42 and D60); 0.25 MOI of BVDV type 1 (D21); and 0.25 and 0.5 MOI of BVDV type 2 (D60) were significantly higher for TRT than CON. IL-17 production induced by 0.25 MOI of BVDV type 1 was significantly higher on D60 for TRT compared to CON. IFN-gamma and IL-10 were not significantly different between treatments. These data indicate feeding OG has a beneficial effect on responses to vaccine antigens in Holstein dairy heifers.

Ambient ammonia does not appear to inhibit the immune response to infectious bronchitis virus vaccination and protection from homologous challenge in broiler chickens.

Commercial broilers are commonly exposed to gaseous ammonia (NH3) originating from degradation of nitrogen-containing excreta in the litter during the grow-out period. Ammonia concentrations in the air are higher in poorly ventilated houses and appear to coincide with the elevated incidence of respiratory disease occurring during the winter months. This study examined the effect of NH3 on the immune response to infectious bronchitis virus (IBV) vaccination and protection against homologous serotype challenge in commercial broiler chickens. One-day-old chicks were administered IBV vaccine and exposed to 30-60 ppm of NH3. At 28 DOA, birds were challenged oculonasally with a pathogenic homologous IBV, and protection was measured by viral detection, clinical signs, ciliostasis, and presence of airsacculitis. IBV-specific serum IgG and lacrimal fluid IgA titers, as well as Harderian gland (HG) immune cell phenotypes, were evaluated. Ammonia exposure was associated with an increased incidence of airsacculitis among non-vaccinated, challenged birds. Vaccinated, NH3-exposed birds were completely protected from IBV challenge. Ammonia had subtle effects on cilia morphology and function but did not affect vaccine or challenge virus replication and clearance, clinical signs, ciliostasis, tracheal histopathology scores, or immune responses. In the HG of vaccinated birds, the percent of leukocytes, MHC I+/MHC IIhi expression, IgM+ expression, and CD8+ expression was increased, while mucosal IgA and serum IgG titers were nominal. Non-vaccinated, IBV-challenged birds exhibited an increased percent of leukocytes, MHC I+/MHC IIhi expression, and IgM+ expression in the HG at 5 dpc, followed by increased mucosal IgA and serum IgG titers and CD8+ expression at 10-14 dpc. In contrast, vaccinated, IBV-challenged birds had a minimal increase in MHC I+/MHC IIhi expression, and serum IgG antibody titers in vaccinated birds increased rapidly. The results indicate that commercial broilers exposed to moderate levels of ambient NH3 are equally protected against IBV challenge if appropriately vaccinated, and the absence of robust immune activation in vaccinated, challenged birds suggests that the challenge virus was efficiently neutralized before establishing infection. In contrast, ambient NH3 exposure was associated with a higher incidence of airsacculitis in non-vaccinated, challenged birds, despite the apparent lack of differences in the immune response between birds in the NH3-exposed and NH3 control groups.

A dose ranging study of 2 different formulations of 15-valent pneumococcal conjugate vaccine (PCV15) in healthy infants.

BACKGROUND: Two new formulations of an investigational 15-valent pneumococcal conjugate vaccine (PCV15-A and PCV15-B) were developed using 2 different protein-polysaccharide conjugation processes and evaluated in separate phase I/II studies (NCT02037984 [V114-004] and NCT02531373 [V114-005]) to assess optimal concentrations of pneumococcal polysaccharide (PnPs) and Aluminum Phosphate Adjuvant. METHODS: Various lots of PCV15-A and PCV15-B containing different concentrations of PnPs and/or adjuvant were compared to PCV13 in young adults and infants. Adults received single dose and infants received 4 doses at 2, 4, 6, and 12-15 months of age. Adverse events (AEs) were collected after each dose. Serotype-specific immunoglobulin G (IgG) concentrations and opsonophagocytic activity (OPA) were measured prior and 30 days postvaccination in adults, at 1 month postdose 3 (PD3), pre-dose4, and postdose 4 (PD4) in infants. RESULTS: Safety profiles were comparable across vaccination groups. At PD3, serotype-specific IgG GMCs were generally lower for either PCV15 formulation than PCV13 for most shared serotypes. PCV15 consistently elicited higher antibody responses to the 2 serotypes unique to the vaccine (22F and 33F) and serotype 3 for which PCV13 was shown to be ineffective. Except for serotypes 6A and 6B, no dose-response effect was observed with increasing concentrations of PnPs and/or adjuvant. CONCLUSION: PCV15 is safe and induces IgG and OPA responses to all 15 serotypes in the vaccine. No significant differences in antibody responses were observed with increases in PnPs and/or Aluminum Phosphate Adjuvant.