Submicron immunoglobulin particles exhibit FcγRII-dependent toxicity linked to autophagy in TNFα-stimulated endothelial cells.

In intravenous immunoglobulins (IVIG), and some other immunoglobulin products, protein particles have been implicated in adverse events. Role and mechanisms of immunoglobulin particles in vascular adverse effects of blood components and manufactured biologics have not been elucidated. We have developed a model of spherical silica microparticles (SiMPs) of distinct sizes 200-2000 nm coated with different IVIG- or albumin (HSA)-coronas and investigated their effects on cultured human umbilical vein endothelial cells (HUVEC).

enhancement of Zika virus infection by preexisting West Nile virus antibodies in human plasma-derived immunoglobulins revealed after P2 binding site-specific enrichment.

Human immunoglobulin preparations contain a diverse range of polyclonal antibodies that reflect past immune responses against pathogens encountered by the blood donor population. In this study, we examined a panel of intravenous immunoglobulins (IGIVs) manufactured over the past two decades (1998-2020) for their capacity to neutralize or enhance Zika virus (ZIKV) infection . These IGIVs were selected specifically based on their production dates in relation to the occurrences of two flavivirus outbreaks in the U.

Nanoluciferase Reporter Zika Viruses as Tools for Assessing Infection Kinetics and Antibody Potency.

Zika virus (ZIKV) has become endemic in multiple tropical and subtropical regions and has the potential to become widespread in countries with limited prior exposure to this infection. One of the most concerning sequelae of ZIKV infection is the teratogenic effect on the developing fetus, with the mechanisms of viral spread to and across the placenta remaining largely unknown. Although vaccine trials and prophylactic or therapeutic treatments are being studied, there are no approved treatments or vaccines for ZIKV.

Interchangeability of the Assays Used to Assess the Activity of Anti-SARS-CoV-2 Monoclonal Antibodies.

The recent global COVID-19 pandemic caused by SARS-CoV-2 lasted for over three years. A key measure in combatting this pandemic involved the measurement of the monoclonal antibody (mAb)-mediated inhibition of binding between the spike receptor-binding domain (RBD) and hACE2 receptor. Potency assessments of therapeutic anti-SARS-CoV-2 mAbs typically include binding or cell-based neutralization assays.

Uses and Challenges of Antiviral Polyclonal and Monoclonal Antibody Therapies.

Viral diseases represent a major public health concerns and ever-present risks for developing into future pandemics. Antiviral antibody therapeutics, either alone or in combination with other therapies, emerged as valuable preventative and treatment options, including during global emergencies. Here we will discuss polyclonal and monoclonal antiviral antibody therapies, focusing on the unique biochemical and physiological properties that make them well-suited as therapeutic agents.

Method for screening influenza neutralizing antibodies in crude human plasma and its derivatives using SPR.

We applied Surface Plasmon Resonance (SPR) technology to develop a method for potency screening and quantification of anti-influenza antibodies in minimally processed human plasma samples and intravenous immunoglobulin (IGIV) products. We found that specific antibodies in human plasma or IGIV capable of inhibiting binding of influenza hemagglutinin to receptor-analogous glycans do so in concentration-dependent manner. We ranked the inhibitory activity of plasma samples from multiple donors and found a good correlation (r = 0.

Immune globulin usage trends in commercially insured and Medicare populations, 2009-2019.

Background: Longitudinal patterns of immune globulins (IG) use have not been described in large populations. Understanding IG usage is important given potential supply limitations impacting individuals for whom IG is the sole life-saving/health-preserving therapy. The study describes US IG utilization patterns from 2009 to 2019.

Thrombogenic potential of picomolar coagulation factor XIa is mediated by thrombin wave propagation.

Inhibitors of coagulation factor XIa (FXIa) are currently being investigated as potential anticoagulant therapies. We hypothesize that circulating FXIa could be a potential target for these therapies. Using previous analyses of FXIa impurities in immune globulin products involved in thrombotic adverse events, we estimated that picomolar levels of FXIa can be thrombogenic.

An optimized microplate-based method to evaluate complement-dependent hemolysis mediated by intravenous immunoglobulins (IVIG).

Hemolytic reactions can cause serious complications after administration of Intravenous Immunoglobulin (IVIG), due to passive transfer of anti-A and anti-B IgG antibodies (isoagglutinins). A maximum allowable amount of isoagglutinins is established in the US and EU for licensed IVIG, as measured by a specified direct hemagglutination test (DHAT). Despite this limit, reports of hemolysis have increased over time, raising the question of how well the DHAT predicts clinically significant hemolysis.

Immune Prophylaxis and Therapy for Human Cytomegalovirus Infection.

Human Cytomegalovirus (HCMV) infection is widespread and can result in severe sequelae in susceptible populations. Primary HCMV infection of naïve individuals results in life-long latency characterized by frequent and sporadic reactivations. HCMV infection elicits a robust antibody response, including neutralizing antibodies that can block the infection of susceptible cells in vitro and in vivo.

Thrombin generation test based on a 96-channel pipettor for evaluation of FXIa procoagulant activity in pharmaceuticals.

Thrombin generation (TG) assays are used widely to investigate both diseases and drugs that impact thrombosis and bleeding. TG assays were also instrumental in the identification of thrombogenic impurities in immune globulin products, which were associated with thrombotic adverse events in patients. TG assays are therefore now used by quality control laboratories of plasma derivative drug manufacturers and regulatory agencies responsible for the safety testing and release of immune globulin products.

Entry and Disposition of Zika Virus Immune Complexes in a Tissue Culture Model of the Maternal-Fetal Interface.

Zika virus (ZIKV) infections have been associated with an increased incidence of severe microcephaly and other neurodevelopmental disorders in newborn babies. Passive immunization with anti-ZIKV neutralizing antibodies has the potential to become a feasible treatment or prophylaxis option during pregnancy. Prior to clinical use, such antibodies should be assessed for their ability to block ZIKV passage to the fetus.

Detecting factor XIa in immune globulin products: Commutability of international reference materials for traditional and global hemostasis assays.

Background: Activated coagulation factor XIa (FXIa) is an impurity and primary source of procoagulant activity in thrombosis-implicated immune globulin (IG) products. Several assays, of varying quality and precision are used to assess FXIa-like procoagulant activity in units relevant to their respective principles.

Objectives: To advance unified reporting, we sought to employ the World Health Organization reference reagents (RRs) to present the results of differing methodologies in units of FXIa activity and rank the sensitivity and robustness of these methodologies.

Combined thrombogenic effects of vessel injury, pregnancy and procoagulant immune globulin administration in mice.

Background: Pregnant women are at increased risk of thrombotic adverse events. Plasma derived immune globulin (IG) products, which are used in pregnancy for various indications, may contain procoagulant impurity activated coagulation factor XI (FXIa). Procoagulant IG products have been associated with increased thrombogenicity but their effect in pregnancy is unknown.

Foster and kinship carer survey: Accessing health services for children in out-of-home care.

Aim: To explore the experiences of Victorian foster and kinship carers in accessing health services for children in their care and to quantify the frequency of potential barriers to health care.

Methods: On-line survey co-designed with the Foster Care Association of Victoria measuring carer-reported health service engagement by a child/young person in their care, ease of service access, time to receiving Medicare number and out-of-pocket health-related costs. A total of 239 foster and 51 kinship carers were recruited through email and social media by carer support agencies.

Health needs and timeliness of assessment of Victorian children entering out-of-home care: An audit of a multidisciplinary assessment clinic.

Aim: To describe the health needs identified in children attending a comprehensive health assessment at a tertiary hospital, multidisciplinary clinic for children following entry to out-of-home care and timeliness of referral and assessment compared with national recommendations.

Methods: This was a retrospective audit of all the children who attended the Pathway to Good Health clinic at The Royal Children's Hospital, Melbourne from May 2013 until 31 August 2016.

Results: A total of 119 children aged 0-12 years attended the clinic during the audit period.

S27 of IFNα1 Contributes to Its Low Affinity for IFNAR2 and Weak Antiviral Activity.

Type I interferons (IFNs) signal by forming a high affinity IFN-IFNAR2 dimer, which subsequently recruits IFNAR1 to form a ternary complex that initiates JAK/STAT signaling. Among the 12 IFNα subtypes, IFNα1 has a uniquely low affinity for IFNAR2 (<100 × of the other IFNα subtypes) and commensurately weak antiviral activity, suggesting an undefined function distinct from suppression of viral infections. Also unique in IFNα1 is substitution of a serine for phenylalanine at position 27, a contact point that stabilizes the IFNα:IFNAR2 hydrophobic interface.

What is the timeliness and extent of health service use of Victorian (Australia) children in the year after entry to out-of-home care? Protocol for a retrospective cohort study using linked administrative data.

Introduction: Children entering out-of-home care have high rates of health needs across all domains of health. To identify these needs early and optimise long-term outcomes, routine health assessment on entry to care is recommended by child health experts and included in policy in many jurisdictions. If effective, this ought to lead to high rates of health service use as needs are addressed.

Characterization of source plasma from self-identified vaccinated or convalescent donors during the 2009 H1N1 pandemic.

Background: Influenza immune globulin, manufactured from plasma of convalescent or vaccinated donors has been proposed as a potential therapy for severe influenza. In 2009, a program was initiated to collect plasma from donors who self-identified as having had H1N1 influenza or having received the H1N1 pandemic vaccine. The goal of this study was to determine the efficiency of donor screening by self-identification without antibody testing, and to evaluate demographic predictors of high-titer donations.

Vitamin K5 is an efficient photosensitizer for ultraviolet A light inactivation of bacteria.

Photodynamic treatment combining light and a photosensitizer molecule can be an effective method to inactivate pathogenic bacteria. This study identified vitamin K5 as an efficient photosensitizer for ultraviolet light A (UVA)-induced bacterial inactivation. Six bacterial species, Bacillus cereus (vegetative form), Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae, and two species of antibiotic-resistant bacteria, Pseudomonas aeruginosa* and Staphylococcus aureus*, were suspended in aqueous solutions with or without vitamin K5 and exposed to UVA irradiation.

Binding and neutralizing anti-cytomegalovirus activities in immune globulin products.

Congenital infection as well as infection of immunocompromised individuals by cytomegalovirus (CMV) can be associated with significant morbidity, mortality, and long-term adverse health outcomes. Assessment of anti-viral activity using appropriate assays is essential for ensuring safe and efficacious use of therapeutic CMV immune globulin (IG) products. In this study, we used commercial ELISA kits to compare anti-CMV antibody binding activity and avidity for lots of CMV-specific and normal IG products available in the US market.