Production of Native Bispecific Antibodies in Rabbits

BACKGROUND: A natural bispecific antibody, which can be produced by exchanging Fab arms of two IgG4 molecules, was first described in allergic patients receiving therapeutic injections with two distinct allergens. However, no information has been published on the production of natural bispecific antibody in animals. Even more important, establishment of an animal model is a useful approach to investigate and characterize the naturally occurring antibody. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that a natural bispecific antibody can also be generated in New Zealand white rabbits by immunization with synthesized conjugates. These antibodies showed bispecificity to the components that were simultaneously used to immunize the animals. We observed a trend in our test animals that female rabbits exhibited stronger bispecific antibody responses than males. The bispecific antibody was monomeric and primarily belonged to immunoglobulin (Ig) G. Moreover, bispecific antibodies were demonstrated by mixing 2 purified monospecific antibodies in vivo and in vitro. CONCLUSIONS/SIGNIFICANCE: Our results extend the context of natural bispecific antibodies on the basis of bispecific IgG4, and may provide insights into the exploration of native bispecific antibodies in immunological diseases

Area of Concern: A new paradigm in life cycle assessment for the development of footprint indicators

Purpose As a class of environmental metrics, footprints have been poorly defined, have shared an unclear relationship to Life Cycle Assessment (LCA), and the variety of approaches to quantification have sometimes resulted in confusing and contradictory messages in the marketplace. In response, a task force operating under the auspices of the UNEP/SETAC Life Cycle Initiative project on environmental Life Cycle Impact Assessment (LCIA) has been working to develop generic guidance for developers of footprint metrics. The purpose of this paper is to introduce a universal footprint definition and related terminology as well as to discuss modelling implications. Methods The task force has worked from the perspective that footprints should be underpinned by the same data systems and models as used in LCA. However, there are important differences in purpose and orientation relative to LCA impact category indicators. Footprints have a primary orientation toward society and nontechnical stakeholders. They are also typically of narrow scope, having the purpose of reporting only in relation to specific topics. In comparison, LCA has a primary orientation toward stakeholders interested in comprehensive evaluation of overall environmental performance and trade-offs among impact categories. These differences create tension between footprints, the existing LCIA framework based on the Area of Protection paradigm, and the core LCA standards ISO14040/44. Results In parallel to Area of Protection, we introduce Area of Concern as the basis for a universal footprint definition. In the same way that LCA uses impact category indicators to assess impacts that follow a common cause-effect pathway toward Areas of Protection, footprint metrics address Areas of Concern. The critical difference is that Areas of Concern are defined by the interests of stakeholders in society rather than the LCA community. In addition, Areas of Concern are stand-alone and not necessarily part of a framework intended for comprehensive environmental performance assessment. The Area of Concern paradigm is needed to support the development of footprints in a way that fulfils their distinctly different purpose. It is also needed as a mechanism to extricate footprints from some of the provisions of ISO 14040/44 which are not considered relevant. Specific issues are identified in relation to double counting, aggregation, and the selection of relevant indicators. Conclusions The universal footprint definition and related terminology introduced in this paper create a foundation that will support the development of footprint metrics in parallel with LCA

LC-IMPACT: a regionalized life cycle damage assessment method

Life cycle impact assessment (LCIA) is a lively field of research, and data and models are continuously improved in terms of impact pathways covered, reliability, and spatial detail. However, many of these advancements are scattered throughout the scientific literature, making it difficult for practitioners to apply the new models. Here, we present the LC-IMPACT method that provides characterization factors at the damage level for 11 impact categories related to three areas of protection (human health, ecosystem quality, natural resources). Human health damage is quantified as disability adjusted life years, damage to ecosystem quality as global species extinction equivalents (based on potentially disappeared fraction of species), and damage to mineral resources as kilogram of extra ore extracted. Seven of the impact categories include spatial differentiation at various levels of spatial scale. The influence of value choices related to the time horizon and the level of scientific evidence of the impacts considered is quantified with four distinct sets of characterization factors. We demonstrate the applicability of the proposed method with an illustrative life cycle assessment example of different fuel options in Europe (petrol or biofuel). Differences between generic and regionalized impacts vary up to two orders of magnitude for some of the selected impact categories, highlighting the importance of spatial detail in LCIA. This article met the requirements for a gold - gold JIE data openness badge described at .Industrial Ecolog

Mainstreaming life cycle thinking through a consistent approach to footprints

Over recent years, footprints have emerged as an important means of reporting environmental performance. Some individual footprints have become quite sophisticated in their calculation procedures. However, as an overallclass of environmental metrics they have been poorly defined, having a variety of conceptual foundations and an unclear relationship to LCA. The variety and sometimes contradictory approaches to quantification have also led to confusing and contradictory messages in the marketplace which have undermined their acceptance by industry and governments.In response, a task force operating under the auspices of the UNEP/SETAC Life Cycle Initiative project on environmental Life Cycle Impact Assessment has been working to develop generic guidance for developers of footprint metrics. The initial work involved forming a consensual position on the difference between footprints and existing LCA impact category indicators. In short, footprints are deemed to have a primary orientation toward society and nontechnical stakeholders and report only on selected topics of concern. On the other hand, LCA impact category indicators have a primary orientation toward technical stakeholders and report in relation to a larger framework designed for comprehensive evaluation of environmental performance and trade-offs. The task force has also developed a universal footprint definition. In parallel to Area of Protection, we introduce Area of Concern. In the same way that LCA uses impact category indicators to assess impacts that follow a common cause-effect pathway toward Areas of rotection, ootprint metrics address Areas of Concern. The critical difference is that Areas of Concern are defined by the interests of stakeholders in society rather than the LCA community. In addition, Areas of Concern are stand-alone and not part of a framework intended for comprehensive environmental performance assessment. Accordingly, footprints are universally defined as metrics used to report life cycle assessment results addressing an Area of Concern