Sowing confusion in the field: the interchangeable use of biosimilar terminology.

The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) created an abbreviated licensure pathway in the United States that allows for the development and approval of biologic products shown to be biosimilar to or interchangeable with a US Food and Drug Administration (FDA)-licensed reference product. FDA released the draft guidance for industry on Demonstrating Interchangeability with a Reference Product (hereafter referred to as the Draft Interchangeability Guidance) in January 2017. Despite FDA's efforts, there continues to be a great deal of confusion and misinformation surrounding the topic of interchangeability.

Neutron Reflectivity as a Tool for Physics-Based Studies of Model Bacterial Membranes.

The principles of neutron reflectivity and its application as a tool to provide structural information at the (sub-) molecular unit length scale from models for bacterial membranes are described. The model membranes can take the form of a monolayer for a single leaflet spread at the air/water interface, or bilayers of increasing complexity at the solid/liquid interface. Solid-supported bilayers constrain the bilayer to 2D but can be used to characterize interactions with antimicrobial peptides and benchmark high throughput lab-based techniques.

Requirement of IL-17RA in Con A induced hepatitis and negative regulation of IL-17 production in mouse T cells.

Th17 cells, a subset of T cells involved in autoimmunity and host defense against extracellular Gram-negative infection, express both IL-17A and IL-17F. Both IL-17A and IL-17F can signal via the IL-17RA; however, IL-17F does so at a 1- to 2-log higher concentration than IL-17A. In this study, we show that the IL-17F homodimer via IL-17RA is a negative regulator of IL-17 production in T cells and suggest a mechanism whereby IL-17RA on T cells serves as an autocrine/paracrine regulator of IL-17 synthesis in T cells.

TH17 cells mediate steroid-resistant airway inflammation and airway hyperresponsiveness in mice.

Steroid-resistant asthma comprises an important source of morbidity in patient populations. T(H)17 cells represent a distinct population of CD4(+) Th cells that mediate neutrophilic inflammation and are characterized by the production of IL-17, IL-22, and IL-6. To investigate the function of T(H)17 cells in the context of Ag-induced airway inflammation, we polarized naive CD4(+) T cells from DO11.

Enhanced defense against Pneumocystis carinii mediated by a novel dectin-1 receptor Fc fusion protein.

Pneumocystis carinii (PC) pneumonia is a leading opportunistic infection found among HIV-infected individuals worldwide. Although CD4(+) T cell deficiency clearly correlates with susceptibility to PC pneumonia, murine models of disease indicate that PC-directed Abs may prevent infection and/or inhibit growth of existing PC within the lungs. Recognition of PC by alveolar macrophages involves the beta-glucan receptor Dectin-1 and macrophage effector function against PC is enhanced by Abs derived from PC-vaccinated hosts.

Regulatory T cells dampen pulmonary inflammation and lung injury in an animal model of pneumocystis pneumonia.

CD4+CD25+FoxP3+ regulatory T cells are decreased in patients infected with HIV and have been shown to be critical in mediating Ag tolerance in the lung. Because a subset of Pneumocystis-infected individuals develop substantial lung injury, which can be modeled in immune reconstituted scid mice, we used mouse models of Pneumocystis carinii to investigate the role of regulatory T cells in opportunistic infection and immune reconstitution. In this study, we show that CD4+CD25+FoxP3+ cells are part of the host response to Pneumocystis in CD4+ T cell-intact mice.

Allergens induce enhanced bronchoconstriction and leukotriene production in C5 deficient mice.

Background: Previous genetic analysis has shown that a deletion in the complement component 5 gene-coding region renders mice more susceptible to allergen-induced airway hyperresponsiveness (AHR) due to reduced IL-12 production. We investigated the role of complement in a murine model of asthma-like pulmonary inflammation.

Methods: In order to evaluate the role of complement B10 mice either sufficient or deficient in C5 were studied.

CXCR3 and IFN protein-10 in Pneumocystis pneumonia.

We have previously shown that Tc1 CD8(+) T cells have in vitro and in vivo effector activity against Pneumocystis (PC) infection in mice. Because these cells have preferential expression of CXCR3, we investigated whether CXCR3 was required for host defense activity against PC. Mice deficient in CXCR3 but CD4(+) T cell intact, showed an initial delay but were able to clear the infectious challenge, indicating that CXCR3 signaling is not essential for clearance of PC.

CXC chemokines modulate IgE secretion and pulmonary inflammation in a model of allergic asthma.

The pathophysiology of asthma is influenced by exposure to allergens and endotoxin. Although the role of allergen-induced eosinophilia has been widely studied, neutrophil-mediated responses remain elusive. A role for neutrophils in the asthmatic responses is likely since human neutrophils have been shown to express IgE receptors, as well as receptors for many cytokines and chemokines implicated in the pathogenesis of asthma.

Prevention and reversal of pulmonary inflammation and airway hyperresponsiveness by dexamethasone treatment in a murine model of asthma induced by house dust.

The morbidity and mortality from asthma in the Western world have increased 75% in the past 20 years. Recent studies have demonstrated that sensitization to cockroach allergens correlates strongly with the increased asthma morbidity for adults and children. We investigated whether dexamethasone administered before or after allergen challenge would inhibit the pulmonary inflammation and airway hyperresponsiveness in a mouse model of asthma induced by a house dust extract with high levels of cockroach allergens.