Systemwide Evaluation of Avian Predation on Juvenile Salmonids from the Columbia River Based on Recoveries of Passive Integrated Transponder Tags

We recovered passive integrated transponder (PIT) tags from nine piscivorous waterbird colonies in the Columbia River basin to evaluate avian predation on Endangered Species Act (ESA)-listed salmonid Oncorhynchus spp. populations during 2007–2010. Avian predation rates were calculated based on the percentage of PIT-tagged juvenile salmonids that were detected as passing hydroelectric dams and subsequently were consumed and deposited by birds on their nesting colonies. Caspian terns Hydroprogne caspia (hereafter, “terns”) and double-crested cormorants Phalacrocorax auritus (hereafter, “cormorants”) nesting on East Sand Island in the Columbia River estuary consumed the highest proportions of available PIT-tagged salmonids, with minimum predation rates ranging from 2.5% for Willamette River spring Chinook salmon O. tshawytscha to 16.0% for Snake River steelhead O. mykiss. Estimated predation rates by terns, cormorants, gulls of two species (California gull Larus californicus and ring-billed gull L. delawarensis), and American white pelicans Pelecanus erythrorhynchos nesting near the confluence of the Snake and Columbia rivers were also substantial; minimum predation rates ranged from 1.4% for Snake River fall Chinook salmon to 13.2% for upper Columbia River steelhead. Predation on ESA-listed salmonids by gulls and American white pelicans were minor (<2.0% per ESA-listed salmonid population) relative to predation by terns and cormorants. Cumulative impacts were greater for Snake River and upper Columbia River salmonids than for salmonids originating closer to the estuary because upriver salmonids must migrate past more bird colonies to reach the ocean. Predation rates adjusted for colony size (per capita rates) were significantly higher for terns and cormorants nesting at inland colonies (upstream of Bonneville Dam) than for those nesting in the estuary, suggesting that inland colonies have a greater reliance on salmonids as a food source. Management actions to increase salmonid survival by reducing avian predation in the estuary could be offset if birds that disperse from the estuary relocate to inland nesting sites on or near the Columbia River.This is the publisher’s final pdf. The article is copyrighted by the American Fisheries Society and published by Taylor & Francis. It can be found at: http://www.tandfonline.com/toc/utaf20/curren

Priming Immunization with DNA Augments Immunogenicity of Recombinant Adenoviral Vectors for Both HIV-1 Specific Antibody and T-Cell Responses

Induction of HIV-1-specific T-cell responses relevant to diverse subtypes is a major goal of HIV vaccine development. Prime-boost regimens using heterologous gene-based vaccine vectors have induced potent, polyfunctional T cell responses in preclinical studies.The first opportunity to evaluate the immunogenicity of DNA priming followed by recombinant adenovirus serotype 5 (rAd5) boosting was as open-label rollover trials in subjects who had been enrolled in prior studies of HIV-1 specific DNA vaccines. All subjects underwent apheresis before and after rAd5 boosting to characterize in depth the T cell and antibody response induced by the heterologous DNA/rAd5 prime-boost combination.rAd5 boosting was well-tolerated with no serious adverse events. Compared to DNA or rAd5 vaccine alone, sequential DNA/rAd5 administration induced 7-fold higher magnitude Env-biased HIV-1-specific CD8(+) T-cell responses and 100-fold greater antibody titers measured by ELISA. There was no significant neutralizing antibody activity against primary isolates. Vaccine-elicited CD4(+) and CD8(+) T-cells expressed multiple functions and were predominantly long-term (CD127(+)) central or effector memory T cells and that persisted in blood for >6 months. Epitopes mapped in Gag and Env demonstrated partial cross-clade recognition.Heterologous prime-boost using vector-based gene delivery of vaccine antigens is a potent immunization strategy for inducing both antibody and T-cell responses.ClinicalTrials.gov NCT00102089, NCT00108654

Problem and Pathological Gambling in a Sample of Casino Patrons

Relatively few studies have examined gambling problems among individuals in a casino setting. The current study sought to examine the prevalence of gambling problems among a sample of casino patrons and examine alcohol and tobacco use, health status, and quality of life by gambling problem status. To these ends, 176 casino patrons were recruited by going to a Southern California casino and requesting that they complete an anonymous survey. Results indicated the following lifetime rates for at-risk, problem, and pathological gambling: 29.2, 10.7, and 29.8%. Differences were found with regards to gambling behavior, and results indicated higher rates of smoking among individuals with gambling problems, but not higher rates of alcohol use. Self-rated quality of life was lower among pathological gamblers relative to non-problem gamblers, but did not differ from at-risk or problem gamblers. Although subject to some limitations, our data support the notion of higher frequency of gambling problems among casino patrons and may suggest the need for increased interventions for gambling problems on-site at casinos

Author Correction: Mosaic nanoparticle display of diverse influenza virus hemagglutinins elicits broad B cell responses.

In the version of this article initially published, the labels (50 Å) above the scale bars in Fig. 1b were incorrect. The correct size is 50 nm. The error has been corrected in the HTML and PDF versions of the article

Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial

SummaryBackgroundThe 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing Zaire Ebola virus glycoprotein (ChAd3-EBO-Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3-EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo).MethodsIn the phase 1, single-blind, randomised trial of ChAd3-EBO-Z in the USA, we recruited adults aged 18–65 years from the University of Maryland medical community and the Baltimore community. In the phase 1b, open-label and double-blind, dose-escalation trial of ChAd3-EBO-Z in Mali, we recruited adults 18–50 years of age from six hospitals and health centres in Bamako (Mali), some of whom were also eligible for a nested, randomised, double-blind, placebo-controlled trial of MVA-BN-Filo. For randomised segments of the Malian trial and for the US trial, we randomly allocated participants (1:1; block size of six [Malian] or four [US]; ARB produced computer-generated randomisation lists; clinical staff did randomisation) to different single doses of intramuscular immunisation with ChAd3-EBO-Z: Malians received 1 × 1010 viral particle units (pu), 2·5 × 1010 pu, 5 × 1010 pu, or 1 × 1011 pu; US participants received 1 × 1010 pu or 1 × 1011 pu. We randomly allocated Malians in the nested trial (1:1) to receive a single dose of 2 × 108 plaque-forming units of MVA-BN-Filo or saline placebo. In the double-blind segments of the Malian trial, investigators, clinical staff, participants, and immunology laboratory staff were masked, but the study pharmacist (MK), vaccine administrator, and study statistician (ARB) were unmasked. In the US trial, investigators were not masked, but participants were. Analyses were per protocol. The primary outcome was safety, measured with occurrence of adverse events for 7 days after vaccination. Both trials are registered with ClinicalTrials.gov, numbers NCT02231866 (US) and NCT02267109 (Malian).FindingsBetween Oct 8, 2014, and Feb 16, 2015, we randomly allocated 91 participants in Mali (ten [11%] to 1 × 1010 pu, 35 [38%] to 2·5 × 1010 pu, 35 [38%] to 5 × 1010 pu, and 11 [12%] to 1 × 1011 pu) and 20 in the USA (ten [50%] to 1 × 1010 pu and ten [50%] to 1 × 1011 pu), and boosted 52 Malians with MVA-BN-Filo (27 [52%]) or saline (25 [48%]). We identified no safety concerns with either vaccine: seven (8%) of 91 participants in Mali (five [5%] received 5 × 1010 and two [2%] received 1 × 1011 pu) and four (20%) of 20 in the USA (all received 1 × 1011 pu) given ChAd3-EBO-Z had fever lasting for less than 24 h, and 15 (56%) of 27 Malians boosted with MVA-BN-Filo had injection-site pain or tenderness.Interpretation1 × 1011 pu single-dose ChAd3-EBO-Z could suffice for phase 3 efficacy trials of ring-vaccination containment needing short-term, high-level protection to interrupt transmission. MVA-BN-Filo boosting, although a complex regimen, could confer long-lived protection if needed (eg, for health-care workers).FundingWellcome Trust, Medical Research Council UK, Department for International Development UK, National Cancer Institute, Frederick National Laboratory for Cancer Research, Federal Funds from National Institute of Allergy and Infectious Diseases

Application of B cell immortalization for the isolation of antibodies and B cell clones from vaccine and infection settings

The isolation and characterization of neutralizing antibodies from infection and vaccine settings informs future vaccine design, and methodologies that streamline the isolation of antibodies and the generation of B cell clones are of great interest. Retroviral transduction to express Bcl-6 and Bcl-xL and transform primary B cells has been shown to promote long-term B cell survival and antibody secretion in vitro, and can be used to isolate antibodies from memory B cells. However, application of this methodology to B cell subsets from different tissues and B cells from chronically infected individuals has not been well characterized. Here, we characterize Bcl-6/Bcl-xL B cell immortalization across multiple tissue types and B cell subsets in healthy and HIV-1 infected individuals, as well as individuals recovering from malaria. In healthy individuals, naïve and memory B cell subsets from PBMCs and tonsil tissue transformed with similar efficiencies, and displayed similar characteristics with respect to their longevity and immunoglobulin secretion. In HIV-1-viremic individuals or in individuals with recent malaria infections, the exhausted CD27-CD21- memory B cells transformed with lower efficiency, but the transformed B cells expanded and secreted IgG with similar efficiency. Importantly, we show that this methodology can be used to isolate broadly neutralizing antibodies from HIV-infected individuals. Overall, we demonstrate that Bcl-6/Bcl-xL B cell immortalization can be used to isolate antibodies and generate B cell clones from different B cell populations, albeit with varying efficiencies

Impact of LS Mutation on Pharmacokinetics of Preventive HIV Broadly Neutralizing Monoclonal Antibodies: A Cross-Protocol Analysis of 16 Clinical Trials in People without HIV

Monoclonal antibodies are commonly engineered with an introduction of Met428Leu and Asn434Ser, known as the LS mutation, in the fragment crystallizable region to improve pharmacokinetic profiles. The LS mutation delays antibody clearance by enhancing binding affinity to the neonatal fragment crystallizable receptor found on endothelial cells. To characterize the LS mutation for monoclonal antibodies targeting HIV, we compared pharmacokinetic parameters between parental versus LS variants for five pairs of anti-HIV immunoglobin G1 monoclonal antibodies (VRC01/LS/VRC07-523LS, 3BNC117/LS, PGDM1400/LS PGT121/LS, 10-1074/LS), analyzing data from 16 clinical trials of 583 participants without HIV. We described serum concentrations of these monoclonal antibodies following intravenous or subcutaneous administration by an open two-compartment disposition, with first-order elimination from the central compartment using non-linear mixed effects pharmacokinetic models. We compared estimated pharmacokinetic parameters using the targeted maximum likelihood estimation method, accounting for participant differences. We observed lower clearance rate, central volume, and peripheral volume of distribution for all LS variants compared to parental monoclonal antibodies. LS monoclonal antibodies showed several improvements in pharmacokinetic parameters, including increases in the elimination half-life by 2.7- to 4.1-fold, the dose-normalized area-under-the-curve by 4.1- to 9.5-fold, and the predicted concentration at 4 weeks post-administration by 3.4- to 7.6-fold. Results suggest a favorable pharmacokinetic profile of LS variants regardless of HIV epitope specificity. Insights support lower dosages and/or less frequent dosing of LS variants to achieve similar levels of antibody exposure in future clinical applications

Pair-Trawl Detection of PIT-Tagged Juvenile Salmonids Migrating in the Columbia River Estuary, 2008 Report of Research.

In 2008, we sampled migrating juvenile Pacific salmonids Oncorhynchus spp. tagged with passive integrated transponder (PIT) tags using a surface pair trawl in the upper Columbia River estuary (rkm 61-83). The cod-end of the trawl was replaced with a cylindrical PIT-tag detection antenna with an 86-cm-diameter fish-passage opening and two detection coils connected in series. The pair trawl was 105 m long with a 91.5-m opening between the wings and a sample depth of 4.9 m. Also during 2008, we finalized the development of a prototype 'matrix' antenna, which was larger than previous antennas by a considerable magnitude. The matrix antenna consisted of 6 coils: a 3-coil front component and a 3-coil rear component, which were separated by 1.5-m of net mesh. The fish-passage opening was 2.5 m wide by 3.0 m tall and was attached to a standard-size pair trawl net. Intermittent sampling with a single crew began on 7 March and targeted yearling Chinook salmon O. tshawytscha and steelhead O. mykiss. Daily sampling using two crews began on 30 April and continued through 14 June; during this period we detected 2.7% of all juvenile salmonids previously detected at Bonneville Dam--a measure of sample efficiency. Sampling with a single crew continued through 20 August and targeted subyearling Chinook salmon. We detected 7,397 yearling Chinook salmon, 2,735 subyearling Chinook salmon, 291 coho salmon O. kisutch, 5,950 steelhead, and 122 sockeye salmon O. nerka in the upper estuary. We deployed the matrix antenna system and the older, cylindrical antenna system (86-cm-diameter fish-passage opening) simultaneously in mid-May 2008 to test matrix detection efficiency. The cylindrical antenna system had been used successfully in 2007 and early 2008. Because distribution of migrating salmonids in the estuary changes rapidly, we felt that a tandem sampling effort between the two systems was the only way to truly evaluate comparative detection efficiency. We deployed both systems within 1 km of each other during a period of high fish densities on 13, 14, and 15 May. Detections of the matrix system surpassed those of the cylindrical system by 53% in 14 h of simultaneous sampling (total detections 716 and 339, respectively). We believe that the higher detection rate observed with the matrix system was due to fewer smolts escaping the trawl entrance and to more smolts readily passing through the larger fish-passage opening. After tandem sampling, we continued exclusive use of the matrix system for the remainder of the 2008 juvenile migration season. Mean survival rates from Lower Granite to Bonneville Dam for yearling Chinook salmon and steelhead were 42% (SE = 3.7%) and 46% (SE = 1.5%), respectively. Over 358,000 PIT-tagged salmonids were transported, and we detected 4,619 of these fish

Multiplexed fluorospot for the analysis of dengue virus- And zika virus-specific and cross-reactive memory B cells

Dengue virus (DENV) and Zika virus (ZIKV) are mosquito-borne pathogens that have a significant impact on human health. Immune sera, mAbs, and memory B cells (MBCs) isolated from patients infected with one DENV type can be cross-reactive with the other three DENV serotypes and even more distantly related flaviviruses such as ZIKV. Conventional ELISPOTs effectively measure Ab-secreting B cells but because they are limited to the assessment of a single Ag at a time, it is challenging to distinguish serotype-specific and cross-reactive MBCs in the same well. We developed a novel multifunction FluoroSpot assay using fluorescently labeled DENV and ZIKV (FLVs) that measures the cross-reactivity of Abs secreted by single B cells. Conjugation efficiency and recognition of FLVs by virus-specific Abs were confirmed by flow cytometry. Using a panel of DENV immune, ZIKV immune, and naive PBMC, FLVs were able to simultaneously detect DENV serotype-specific, ZIKV-specific, DENV serotype cross-reactive, and DENV/ZIKV cross-reactive Abs secreted by individual MBCs. Our findings indicate that the FLVs are sensitive and specific tools to detect specific and cross-reactive MBCs. These reagents will allow the assessment of the breadth as well as the durability of DENV/ZIKV B cell responses following vaccination or natural infection. This novel approach using FLVs in a FluoroSpot assay can be applied to other diseases such as influenza in which prior immunity with homosubtype- or heterosubtype-specific MBCs may influence subsequent infections. The Journ Al of Immunology, 2018, 201: 3804-3814