No evidence for enhanced disease with human polyclonal SARS-CoV-2 antibody in the ferret model.

Since SARS-CoV-2 emerged in late 2019, it spread from China to the rest of the world. An initial concern was the potential for vaccine- or antibody-dependent enhancement (ADE) of disease as had been reported with other coronaviruses. To evaluate this, we first developed a ferret model by exposing ferrets to SARS-CoV-2 by either mucosal inoculation (intranasal/oral/ocular) or inhalation using a small particle aerosol. Mucosal inoculation caused a mild fever and weight loss that resolved quickly; inoculation via either route resulted in virus shedding detected in the nares, throat, and rectum for 7-10 days post-infection. To evaluate the potential for ADE, we then inoculated groups of ferrets intravenously with 0.1, 0.5, or 1 mg/kg doses of a human polyclonal anti-SARS-CoV-2 IgG from hyper-immunized transchromosomic bovines (SAB-185). Twelve hours later, ferrets were challenged by mucosal inoculation with SARS-CoV-2. We found no significant differences in fever, weight loss, or viral shedding after infection between the three antibody groups or the controls. Signs of pathology in the lungs were noted in infected ferrets but no differences were found between control and antibody groups. The results of this study indicate that healthy, young adult ferrets of both sexes are a suitable model of mild COVID-19 and that low doses of specific IgG in SAB-185 are unlikely to enhance the disease caused by SARS-CoV-2.

'Insulin is super dangerous if you don't know what you're doing': Situating the risks of insulin within the image and performance enhancing drug community.

INTRODUCTION: Insulin is an essential treatment within diabetes management; however, it takes on a role of enhancement within image and performance enhancing drug (IPED) communities due to its anabolic effects. This study sought to provide insight into how IPED users perceive and manage the risks linked to insulin. METHODS: We conducted semi-structured interviews with 10 individuals from Australia and United Kingdom who used insulin as part of their IPED protocols. The analysis followed an iterative categorisation approach and applied the lens of situated rationality theory. RESULTS: The decision to incorporate insulin was influenced by peers' experiences and preferences. Participants highlighted the risks and responsibilities associated with insulin use, emphasising the need for precise lifestyle habits. They recognised the potential dangers and called for comprehensive harm reduction strategies within IPED communities to respond to such concerns. Some participants expressed reluctance to discuss insulin openly, underlining the importance of education and awareness to mitigate health risks associated with underground and uninformed use. DISCUSSION AND CONCLUSIONS: While people who use IPEDs demonstrate awareness of the risks associated with insulin, their practices of routinisation moderate these risks within the context of IPED use. Silence as a risk-reduction strategy highlights vulnerabilities among certain prospective users, while the hierarchical structure of IPED use establishes expertise and status within the community. Reconsidering insulin risks entails reframing harm reduction messages to better match the social dynamics of IPED communities. Closer ties between IPED communities can enhance support accessibility, particularly through peers, who, with their firsthand knowledge, can offer tailored guidance.

Across the spectrum of legality: The market activities of influencers specialized in steroids and other performance and image enhancing drugs.

BACKGROUND: Like many other goods and services, performance and image enhancing drugs (PIEDs), and particularly androgenic anabolic steroids (AAS), are increasingly discussed and promoted by social media influencers. Little, however, is known about the influencers specialized in PIEDs and which drugs and services they promote and sell. AIMS: Against this background, the study has been intended to identify prominent influencers specialized in PIEDs, examine the market activities they engage in, and assess the latter's legality. METHODS: We first searched the clean internet to identify prominent PIED influencers. Second, we conducted a six-month-long, non-reactive digital ethnography of the social media accounts of 20 influencers and, via a content analysis, identified the market activities they engage in. Third, we assessed the latter's legality, primarily using the EU legislation as a benchmark. FINDINGS: The selected influencers are all current or former bodybuilders, predominantly male and from the United States. Many of them have developed a considerable number of followers, in three cases exceeding one million. They engage in various market activities that span the whole spectrum of legality, from legal to illegal, with many activities having an uncertain, but often dubious, legal status. CONCLUSIONS: Though they may promote harm reduction for some users, PIED influencers also promote the public acceptance of PIED use beyond the bodybuilding community and enhance access to PIEDs for millions of people. Multifaceted policy interventions are required, aiming at preventing influencers from becoming a major source of information on, and route of access to, PIEDs.

Transchromosomic bovine-derived anti-SARS-CoV-2 polyclonal human antibodies protects hACE2 transgenic hamsters against multiple variants.

Pandemic SARS-CoV-2 has undergone rapid evolution resulting in the emergence of many variants with mutations in the spike protein, some of which appear to evade antibody neutralization, transmit more efficiently, and/or exhibit altered virulence. This raises significant concerns regarding the efficacy of anti-S monoclonal antibody-based therapeutics which have failed against variant SARS-CoV-2 viruses. To address this concern, SAB-185, a human anti-SARS-CoV-2 polyclonal antibody was generated in the DiversitAb platform. SAB-185 exhibited equivalent, robust in vitro neutralization for Munich, Alpha, Beta, Gamma, and Δ144-146 variants and, although diminished, retained PRNT50 and PRNT80 neutralization endpoints for Delta and Omicron variants. Human ACE2 transgenic Syrian hamsters, which exhibit lethal SARS-CoV-2 disease, were protected from mortality after challenge with the Munich, Alpha, Beta, Delta, and Δ144-146 variants and clinical signs after non-lethal Omicron BA.1 infection. This suggests that SAB-185 may be an effective immunotherapy even in the presence of ongoing viral mutation.

A fully human monoclonal antibody possesses antibody-dependent cellular cytotoxicity (ADCC) activity against the H1 subtype of influenza A virus by targeting a conserved epitope at the HA1 protomer interface.

The DiversitabTM system produces target specific high titer fully human polyclonal IgG immunoglobulins from transchromosomic (Tc) bovines shown to be safe and effective against multiple virulent pathogens in animal studies and Phase 1, 2 and 3 human clinical trials. We describe the functional properties of a human monoclonal antibody (mAb), 38C2, identified from this platform, which recognizes recombinant H1 hemagglutinins (HAs) and induces appreciable antibody-dependent cellular cytotoxicity (ADCC) activity in vitro. Interestingly, 38C2 monoclonal antibody demonstrated no detectable neutralizing activity against H1N1 virus in both hemagglutination inhibition and virus neutralization assays. Nevertheless, this human monoclonal antibody induced appreciable ADCC against cells infected with multiple H1N1 strains. The HA-binding activity of 38C2 was also demonstrated in flow cytometry using Madin-Darby canine kidney cells infected with multiple influenza A H1N1 viruses. Through further investigation with the enzyme-linked immunosorbent assay involving the HA peptide array and 3-dimensional structural modeling, we demonstrated that 38C2 appears to target a conserved epitope located at the HA1 protomer interface of H1N1 influenza viruses. A novel mode of HA-binding and in vitro ADCC activity pave the way for further evaluation of 38C2 as a potential therapeutic agent to treat influenza virus infections in humans.

Polyclonal Antibodies Derived from Transchromosomic Bovines Vaccinated with the Recombinant F1-V Vaccine Increase Bacterial Opsonization In Vitro and Protect Mice from Pneumonic Plague.

Plague is an ancient disease that continues to be of concern to both the public health and biodefense research communities. Pneumonic plague is caused by hematogenous spread of Yersinia pestis bacteria from a ruptured bubo to the lungs or by directly inhaling aerosolized bacteria. The fatality rate associated with pneumonic plague is significant unless effective antibiotic therapy is initiated soon after an early and accurate diagnosis is made. As with all bacterial pathogens, drug resistance is a primary concern when developing strategies to combat these Yersinia pestis infections in the future. While there has been significant progress in vaccine development, no FDA-approved vaccine strategy exists; thus, other medical countermeasures are needed. Antibody treatment has been shown to be effective in animal models of plague. We produced fully human polyclonal antibodies in transchromosomic bovines vaccinated with the recombinant F1-V plague vaccine. The resulting human antibodies opsonized Y. pestis bacteria in the presence of RAW264.7 cells and afforded significant protection to BALB/c mice after exposure to aerosolized Y. pestis. These data demonstrate the utility of this technology to produce large quantities of non-immunogenic anti-plague human antibodies to prevent or possibly treat pneumonic plague in human.

Phase 2 Safety and Antiviral Activity of SAB-185, a Novel Polyclonal Antibody Therapy for Nonhospitalized Adults With COVID-19.

BACKGROUND: SAB-185, a novel fully human IgG polyclonal immunoglobulin product, underwent phase 2 evaluation for nonhospitalized adults with mild-moderate coronavirus disease 2019 (COVID-19). METHODS: Participants received intravenous SAB-185 3840 units/kg (low-dose) or placebo, or 10 240 units/kg (high-dose) or placebo. Primary outcome measures were nasopharyngeal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA < lower limit of quantification (LLOQ) at study days 3, 7, and 14, time to symptomatic improvement, and safety through day 28. RESULTS: Two-hundred thirteen participants received low-dose SAB-185/placebo (n = 107/106) and 215 high-dose SAB-185/placebo (n = 110/105). The proportions with SARS-CoV-2 RNA < LLOQ were higher for SAB-185 versus placebo at days 3 and 7 and similar at day 14, and significantly higher at day 7 for high-dose SAB-185 versus placebo only, relative risk 1.23 (95% confidence interval, 1.01-1.49). At day 3, SARS-CoV-2 RNA levels were lower with low-dose and high-dose SAB-185 versus placebo: differences in medians of -0.78 log10 copies/mL (P = .08) and -0.71 log10 copies/mL (P = .10), respectively. No difference was observed in time to symptom improvement: median 11/10 days (P = .24) for low-dose SAB-185/placebo and 8/10 days (P = .50) for high-dose SAB-185/placebo. Grade ≥3 adverse events occurred in 5%/13% of low-dose SAB-185/placebo and 9%/12% of high-dose SAB-185/placebo. CONCLUSIONS: SAB-185 was safe and generally well tolerated and demonstrated modest antiviral activity in predominantly low-risk nonhospitalized adults with COVID-19. Clinical Trials Registration. NCT04518410.

Skin Swabbing for Staphylococcus aureus-Targeting Phages.

INTRODUCTION: Staphylococcus aureus (SA) is a major human bacterial pathogen increasingly refractory to antibiotics. Given the dearth of novel antibiotics in the developmental pipeline, we require concerted efforts at optimizing novel antimicrobial approaches. One promising option is the utilization of bacteriophage (phage) therapy, which has been resurrected as a viable clinical therapeutic. Specifically, an expanded library of phages targeting SA is desired. We surmised that SA-targeting phages would be readily accessible as a major component of the cutaneous microbiome. Specifically, we sought to discern if easily accessible (convenient) and discrete anatomic locations, including the nares, axilla, fingernails, toenails, and web spaces, could provide intact phages via a noninvasive, expedient procedure involving swabbing. METHODS: One hundred subjects participated in systematic skin swab specimen collections. Pooled samples were subject to phage harvesting utilizing the soft agar overlay technique. The approval was secured from the Naval Medical Research Center Institutional Review Board (NMRC 2018.0004 FWA00000152). We utilized the same procedures from known samples containing SA-targeting phages. As another positive control, we employed the same swab and acquired samples from an active wound infection. RESULTS: As anticipated, there were no adverse events, and the procedure was successfully implemented within the projected 10-minute duration. No phages were identified exploiting this methodology. Positive controls from various environmental samples identified SA-targeting phages as did the wound effluent sample. CONCLUSIONS: Skin swabbing at multiple anatomic sites from 100 adults yielded insufficient biomass for phage recovery. The negative results provide helpful information for future phage isolation attempts. The lessons learned on why this study failed to isolate phages can be easily utilized by others. With a desire to increase our SA-targeting phage library in pursuit of future clinical trials, and acknowledging the paucity of these phages accessible via traditional recovery from environmental sources, we will next acquire large volumes of wound effluent from confirmed infected wounds with SA to optimize the biomass for phage recovery.

Divergence and Dissonance in Residents' Reported and Actual Feedback to Faculty in a Military Context.

INTRODUCTION: Trainees (e.g., residents) are an obvious and common source of feedback for faculty; however, gaps exist in our understanding of their experiences and practices of providing such feedback. To gain a deeper understanding, this study examined residents' beliefs about what feedback is important to provide, the kinds of feedback they report giving, and the feedback they actually gave. MATERIALS AND METHODS: Descriptive statistics were used to analyze residents' perceptions and feedback behaviors (n = 42/96). Thematic analysis was used to analyze end-of-rotation faculty assessments from 2018 to 2019 (n = 559) to explore the actual written feedback residents provided to the faculty. RESULTS: The findings suggest that residents experience workload constraints (e.g., too many feedback requests), feel that their feedback is not valuable or relevant, and place conditions on when and what feedback is given (e.g., faculty agreeableness, prefer giving positively oriented feedback, and uncomfortable giving negative feedback). When comparing what feedback residents rated as important with the kinds of feedback they reported giving and actually gave, the findings also suggest that there were consistencies (e.g., clinical instruction and professionalism) and inconsistencies (e.g., evidence-based practice and medical knowledge) that may limit constructive feedback for faculty. CONCLUSIONS: Taken together, the findings suggest that trainee assessments of faculty may be insufficient as a primary source of feedback to support the improvement of faculty performance. Potential solutions are discussed.

Sulfidation and Reoxidation of U(VI)-Incorporated Goethite: Implications for U Retention during Sub-Surface Redox Cycling.

Over 60 years of nuclear activity have resulted in a global legacy of contaminated land and radioactive waste. Uranium (U) is a significant component of this legacy and is present in radioactive wastes and at many contaminated sites. U-incorporated iron (oxyhydr)oxides may provide a long-term barrier to U migration in the environment. However, reductive dissolution of iron (oxyhydr)oxides can occur on reaction with aqueous sulfide (sulfidation), a common environmental species, due to the microbial reduction of sulfate. In this work, U(VI)-goethite was initially reacted with aqueous sulfide, followed by a reoxidation reaction, to further understand the long-term fate of U species under fluctuating environmental conditions. Over the first day of sulfidation, a transient release of aqueous U was observed, likely due to intermediate uranyl(VI)-persulfide species. Despite this, overall U was retained in the solid phase, with the formation of nanocrystalline U(IV)O2 in the sulfidized system along with a persistent U(V) component. On reoxidation, U was associated with an iron (oxyhydr)oxide phase either as an adsorbed uranyl (approximately 65%) or an incorporated U (35%) species. These findings support the overarching concept of iron (oxyhydr)oxides acting as a barrier to U migration in the environment, even under fluctuating redox conditions.

Increased Antibody Avidity and Cross-Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2 Variants by Hyperimmunized Transchromosomic Bovine-Derived Human Immunoglobulins for Treatment of Coronavirus Disease 2019.

Passive antibody immunotherapeutics directed against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are promising countermeasures for protection and treatment of coronavirus disease 2019 (COVID-19). SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) can impact the clinical efficacy of immunotherapeutics. A fully human polyclonal antibody immunotherapeutic purified from plasma of transchromosomic (Tc) bovines hyperimmunized with SARS-CoV-2 WA-1 spike (SAB-185) is being assessed for efficacy in a phase 2/3 clinical trial when different circulating SARS-CoV-2 variants predominated. We evaluated antibody binding, avidity maturation, and SARS-CoV-2 VOCs/VOIs virus-neutralizing capacity of convalescent plasma compared with different lots of SAB-185 and individual Tc bovine sera sequentially obtained after each vaccination against Alpha, Epsilon, Iota, Gamma, Beta, Kappa, and Delta variants. In contrast to convalescent plasma, sera and SAB-185 derived from hyperimmunized Tc bovines demonstrated higher antibody avidity and more potent cross-neutralizing activity of VOCs/VOIs. Thus, SAB-185 is a potential promising therapeutic candidate for the treatment of patients infected with SARS-CoV-2 variants.

Human immunoglobulin from transchromosomic bovines hyperimmunized with SARS-CoV-2 spike antigen efficiently neutralizes viral variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with amino-acid substitutions and deletions in spike protein (S) can reduce the effectiveness of monoclonal antibodies (mAbs) and may compromise immunity induced by vaccines. We report a polyclonal, fully human, anti-SARS-CoV-2 immunoglobulin produced in transchromosomic bovines (Tc-hIgG-SARS-CoV-2) hyperimmunized with two doses of plasmid DNA encoding the SARS-CoV-2 Wuhan strain S gene, followed by repeated immunization with S protein purified from insect cells. The resulting Tc-hIgG-SARS-CoV-2, termed SAB-185, efficiently neutralizes SARS-CoV-2, and vesicular stomatitis virus (VSV) SARS-CoV-2 chimeras in vitro. Neutralization potency was retained for S variants including S477N, E484K, and N501Y, substitutions present in recent variants of concern. In contrast to the ease of selection of escape variants with mAbs and convalescent human plasma, we were unable to isolate VSV-SARS-CoV-2 mutants resistant to Tc-hIgG-SARS-CoV-2 neutralization. This fully human immunoglobulin that potently inhibits SARS-CoV-2 infection may provide an effective therapeutic to combat COVID-19.

Protection of human ACE2 transgenic Syrian hamsters from SARS CoV-2 variants by human polyclonal IgG from hyper-immunized transchromosomic bovines.

Pandemic SARS CoV-2 has been undergoing rapid evolution during spread throughout the world resulting in the emergence of many Spike protein variants, some of which appear to either evade antibody neutralization, transmit more efficiently, or potentially exhibit increased virulence. This raises significant concerns regarding the long-term efficacy of protection elicited after primary infection and/or from vaccines derived from single virus Spike (S) genotypes, as well as the efficacy of anti-S monoclonal antibody based therapeutics. Here, we used fully human polyclonal human IgG (SAB-185), derived from hyperimmunization of transchromosomic bovines with DNA plasmids encoding the SARS-CoV-2 Wa-1 strain S protein or purified ectodomain of S protein, to examine the neutralizing capacity of SAB-185 in vitro and the protective efficacy of passive SAB-185 antibody (Ab) transfer in vivo . The Ab preparation was tested for neutralization against five variant SARS-CoV-2 strains: Munich (Spike D614G), UK (B.1.1.7), Brazil (P.1) and SA (B.1.3.5) variants, and a variant isolated from a chronically infected immunocompromised patient (Spike Δ144-146). For the in vivo studies, we used a new human ACE2 (hACE2) transgenic Syrian hamster model that exhibits lethality after SARS-Cov-2 challenge and the Munich, UK, SA and Δ144-146 variants. SAB-185 neutralized each of the SARS-CoV-2 strains equivalently on Vero E6 cells, however, a control convalescent human serum sample was less effective at neutralizing the SA variant. In the hamster model, prophylactic SAB-185 treatment protected the hamsters from fatal disease and minimized clinical signs of infection. These results suggest that SAB-185 may be an effective treatment for patients infected with SARS CoV-2 variants.

Understanding the Importance of Fatherhood among Men Living with HIV in Ontario.

While pregnancy and motherhood have become paramount clinical issues for women living with HIV, parenting has received less attention among men living with HIV (MLWH). We conducted a secondary analysis of a cross-sectional study assessing fertility desires and intentions of MLWH using a 5-point Likert scale based on the question: "Being a father is important to me". Logistic regression models were fit to calculate unadjusted and adjusted odds ratios (ORs) and confidence intervals (CIs) for significant correlates. Of the 276 respondents, 118 were heterosexual, 158 were gay, bisexual, 2-spirit, or queer (GBTQ), 55% had never parented before, and 65% wanted to parent. 191 (69%) respondents agreed that fatherhood was important to them. In unadjusted analyses, heterosexuality (OR 1.52; 95% CI 1.15 to 2.03), African/Caribbean/Black ethnicity (OR 1.57; 95% CI 1.12 to 2.19), African/Caribbean birthplace (OR 1.48; 95% CI 1.06 to 2.05), and history of parenting (OR 1.60; 95% CI 1.10 to 2.39) were significantly (p < 0.05) associated with importance of fatherhood. However, none of these variables were significant in adjusted analyses. From the unadjusted model, factors such as sexual orientation, ethnicity, and current parenthood may influence how MLWH value fatherhood, suggesting HIV and fatherhood is complex and must be explored further.

Wrist-Spanning Fixation of Radiocarpal Dislocation: A Cadaveric Assessment of Ulnar Translation.

Background: Radiocarpal dislocations represent a high-energy wrist injury that can occur with or without concomitant fractures about the wrist. Poor outcomes are often due to radiocarpal instability and secondary ulnar translation. The purpose of this cadaveric study is to determine if there is any difference in the radiographic parameters in a wrist dislocation model given the different location of distal fixation. Methods: Ten paired fresh cadaver upper extremities were fluoroscopically evaluated with posterior-anterior (PA) and lateral views. We created a radiocarpal dislocation model and applied a dorsal bridge plate to either the second or third metacarpal. Repeat PA and lateral fluoroscopic views were obtained for evaluation of radial inclination, radial height, volar tilt, ulnar variance, radiolunate angle, radioscaphoid angle, scapholunate angle, radial rotation index, and four indices for ulnar translation (Taleisnik, Gilula, McMurtry, and Chamay). Results: Bridge plate application to the second metacarpal resulted in a significantly greater incidence of ulnar translation compared to the third metacarpal. Application to either metacarpal resulted in extension of the carpus relative to the radius. Conclusions: A more anatomic radiocarpal relationship was restored more often when distal fixation of the dorsal wrist-spanning bridge plate was applied to the third metacarpal. Further investigation is warranted to determine clinical relevance of these findings in conjunction with clinical and radiographic outcomes.

Bipolar Disruption of the Lateral Ulnar Collateral Ligament of the Elbow: A Case Report.

CASE: The lateral ulnar collateral ligament (LUCL) is one of the primary stabilizers of the elbow. Disruption typically occurs from the humeral origin and may be because of an elbow dislocation or fracture/dislocation. If not identified and properly managed, posterolateral rotatory instability may result from LUCL insufficiency. We describe the case of a patient with bipolar LUCL disruption consisting of an avulsion fracture of the crista supinatoris and a soft-tissue avulsion from the lateral epicondyle. CONCLUSION: Bipolar disruption of the LUCL is a previously unreported injury pattern that may lead to posterolateral instability if not identified and treated.

Ulnohumeral Bridge Plating for Massive Distal Humerus Bone Loss: A Case Report.

CASE: Massive bone loss around the elbow is a challenging clinical condition. Short periarticular osseous segments present few reconstructive options in the setting of distal humerus bone loss. We report the case of a 20-year-old man who sustained an open, intra-articular distal humerus fracture with a massive metaphyseal defect of 15 cm after a motorcycle accident. The defect was reconstructed using an induced membrane technique with temporary ulnohumeral bridge plate stabilization. CONCLUSION: Temporary ulnohumeral spanning plate fixation is a reliable method for periarticular reconstruction in the setting of massive distal humerus bone loss.

Xen45 Gel Stent implant: patient reported outcomes.

Our aim was to report quality of life (QOL) outcomes following Xen45 Gel Stent implantation surgery in patients suffering with primary open angle glaucoma (POAG). A retrospective analysis was performed on all patients who had Xen45 implantation surgery during a 2-year period (Jun, 2016-Apr, 2018). Of 52 consecutive patients were included with a total of 58 eyes being operated on. QOL was compared both pre-operatively and 6 weeks post-operatively using the GQL-15 questionnaire. There was an overall improvement in GQL-15 summary scores for our patient group. All item scores showed either no change or some degree of improvement. The Xen45 Gel Stent Implant is a promising new intervention which has shown improved QOL scores in our patient group. Further, higher power studies are now needed to compare the Xen45 to trabeculectomy (TE), which is currently the gold standard.

Influence of sample collection tube method, anticoagulant-containing plasma versus serum, on influenza virus hemagglutination inhibition titer and microneutralization titer serological assays.

BACKGROUND: The hemagglutination-inhibition (HAI) assay is a critical component for measurement of immunogenicity in influenza vaccine development. It is unknown if the results can be influenced by sample type and anticoagulants. The purpose of this study was to evaluate the influence of different sample collection methods, in particular different anticoagulants, and choice of plasma or serum, on influenza virus serological assays. METHODS: Blood samples from thirty donors previously immunized against influenza viruses were collected using six different types of blood collection tubes, two of which collect serum and four of which contain various anticoagulants for collecting plasma. Serum: (1) serum separator tubes (SST); and (2) Plus Plastic serum "red-top serum" tubes. Plasma: (3) spray-coated K2 ethylenediaminetetraacetic acid (EDTA) tubes: (4) Sodium Heparin tubes; (5) Citrate tubes with 3.2% sodium citrate solution; and (6) Glass Blood Collection tubes with acid citrate dextrose. Samples were tested against three different influenza viruses (A/California/07/2009 (H1N1pdm09), A/Texas/50/2012 (H3N2), and B/Massachusetts/2/2012) for hemagglutination inhibition titer and virus neutralization titer via a microneutralization (MN) assay, and data compared to that obtained for standard serum sample collected in SST. RESULTS: HAI and MN titers against type A viruses were within two dilutions compared to SST collection method over 96% of the time irrespective of sample type or anticoagulant. However, HAI titers for type B virus were more variable across different collection methods. EDTA plasma samples were greater than two dilutions higher than SST serum samples 70% (21 of 30 samples) of the time. In contrast, MN titers were within two dilutions over 96% of the time, with the highest deviation noted in acid citrate dextrose plasma samples (3 of 30 samples tested, 10%). CONCLUSIONS: These data provide useful guidelines for sample collection and serology testing when screening: (i) influenza vaccine immunogenicity antibody response; (ii) antibody responses to newly emerging viral strains; and (iii) clinical samples for anti-influenza antibody activity.

Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate.

Transchromosomic bovines (Tc-bovines) adaptively produce fully human polyclonal immunoglobulin (Ig)G antibodies after exposure to immunogenic antigen(s). The National Interagency Confederation for Biological Research and collaborators rapidly produced and then evaluated anti-Ebola virus IgG immunoglobulins (collectively termed SAB-139) purified from Tc-bovine plasma after sequential hyperimmunization with an Ebola virus Makona isolate glycoprotein nanoparticle vaccine. SAB-139 was characterized by several in vitro production, research, and clinical level assays using wild-type Makona-C05 or recombinant virus/antigens from different Ebola virus variants. SAB-139 potently activates natural killer cells, monocytes, and peripheral blood mononuclear cells and has high-binding avidity demonstrated by surface plasmon resonance. SAB-139 has similar concentrations of galactose-α-1,3-galactose carbohydrates compared with human-derived intravenous Ig, and the IgG1 subclass antibody is predominant. All rhesus macaques infected with Ebola virus/H.sapiens-tc/GIN/2014/Makona-C05 and treated with sufficient SAB-139 at 1 day (n = 6) or 3 days (n = 6) postinfection survived versus 0% of controls. This study demonstrates that Tc-bovines can produce pathogen-specific human Ig to prevent and/or treat patients when an emerging infectious disease either threatens to or becomes an epidemic.