Summary
Based on their mechanisms‐of‐action, CD20 monoclonal antibodies (mAbs) are grouped into Type I complement‐dependent cytotoxicity (CDC) and antibody‐dependent cell‐mediated cytotoxicity (ADCC) ...and Type II programmed cell death (PCD) and ADCC mAbs. We generated 17 new hybridomas producing CD20 mAbs of different isotypes and determined unique heavy and light chain sequence pairs for 13 of them. We studied their epitope binding, binding kinetics and structural properties and investigated their predictive value for effector functions, i.e. PCD, CDC and ADCC. Peptide mapping and CD20 mutant screens revealed that 10 out of these 11 new mAbs have an overlapping epitope with the prototypic Type I mAb rituximab, albeit that distinct amino acids of the CD20 molecule contributed differently. Binding kinetics did not correlate with the striking differences in CDC activity among the mIgG2c mAbs. Interestingly, chimerization of mAb m1 resulted in a mAb displaying both Type I and II characteristics. PCD induction was lost upon introduction of a mutation in the framework of the heavy chain affecting the elbow angle, supporting that structural changes within this region can affect functional activities of CD20 mAbs. Together, these new CD20 mAbs provide further insights in the properties dictating the functional efficacy of CD20 mAbs.
Summary
Based on their mechanisms‐of‐action,
CD
20 monoclonal antibodies (
mA
bs) are grouped into Type I complement‐dependent cytotoxicity (
CDC
) and antibody‐dependent cell‐mediated cytotoxicity (
...ADCC
) and Type
II
programmed cell death (
PCD
) and
ADCC
mA
bs. We generated 17 new hybridomas producing
CD
20
mA
bs of different isotypes and determined unique heavy and light chain sequence pairs for 13 of them. We studied their epitope binding, binding kinetics and structural properties and investigated their predictive value for effector functions, i.e.
PCD
,
CDC
and
ADCC
. Peptide mapping and
CD
20 mutant screens revealed that 10 out of these 11 new
mA
bs have an overlapping epitope with the prototypic Type I
mA
b rituximab, albeit that distinct amino acids of the
CD
20 molecule contributed differently. Binding kinetics did not correlate with the striking differences in
CDC
activity among the
mIgG
2c
mA
bs. Interestingly, chimerization of
mA
b m1 resulted in a
mA
b displaying both Type I and
II
characteristics.
PCD
induction was lost upon introduction of a mutation in the framework of the heavy chain affecting the elbow angle, supporting that structural changes within this region can affect functional activities of
CD
20
mA
bs. Together, these new
CD
20
mA
bs provide further insights in the properties dictating the functional efficacy of CD20
mA
bs.
Purpose
The impact of applying circular strategies to products is often measured through life cycle assessment (LCA). While LCA estimates and compares the impacts of circular products, its ability to ...integrate consumer behaviour is currently limited. The integration of consumer behavioural insights is especially relevant in the packaging sector, where consumer actions at the end-of-life are crucial for the success of circular strategies. This study explores integrating behavioural insights from consumer behaviour sciences (including psychology, sociology and socio-technical approaches) into LCA for a better assessment and design of circular packaging.
Methods
Through a scoping review, scientific literature was mapped to (1) investigate the current integration of consumer behaviour aspects within packaging LCAs and (2) explore the behavioural determinants influencing the recycling and reusing of circular packaging. By building on the insights from these reviews, this study provides recommendations on how to integrate behavioural insights with LCA to assess the impact of circular packaging systems.
Results and discussion
The results indicate that LCA studies for packaging are generally based on assumptions on consumer behaviour, reducing their utility for circular decision-making. The main methods currently used to integrate behaviour variability are scenario and sensitivity analysis, with some studies using consumer profiles and behaviour research to support LCA modelling. Socio-technical approaches, e.g. agent-based modelling or system dynamics, have not been applied yet to integrate a behavioural perspective into the LCA of circular packaging, while this may be a promising avenue. The behaviour science literature covered several predictors found to be important to understand packaging reuse and recycling behaviour. Our review shows that attitudinal and value dimensions have consistently been found to influence both packaging reuse and recycling behaviour, while the latter is also strongly driven by control factors. While LCA modellers can obtain behavioural insights from the behavioural literature, the step of transforming these insights into quantifiable behaviour patterns still needs to be taken. Such endeavours can help to translate individual behaviour predictors into behavioural patterns regarding packaging reuse and recycling.
Conclusions
Consumer behaviour is currently not widely considered in the LCA of circular packaging. Insights from consumer behaviour sciences can contribute to LCA studies in two main ways: defining consumer profiles and modelling socio-technical parameters. Consumer profiles could be drawn from the psychological behaviour literature, while socio-technical approaches can provide models of system behaviour where the interaction of different system actors and items is quantitatively modelled and coupled with LCA models.
Alzheimer's disease (AD) is the most common neurodegenerative disease, with an increasing prevalence. Currently, there is no ideal diagnostic molecular imaging agent for diagnosing AD. Antibodies ...(Abs) have been proposed to close this gap as they can bind selectively and with high affinity to amyloid β (Aβ)—one of the molecular hallmarks of AD. Abs can even be designed to selectively bind Aβ oligomers or isoforms, which are difficult to target with small imaging agents. Conventionally, Abs must be labeled with long-lived radionuclides which typically results in in high radiation burden to healthy tissue. Pretargeted imaging could solve this challenge as it allows for the use of short-lived radionuclides. To develop pretargeted imaging tools that can enter the brain, AD mouse models are useful as they allow testing of the imaging approach in a relevant animal model that could predict its clinical applicability. Several mouse models for AD have been developed with different characteristics. Commonly used models are: 5xFAD, APP/PS1 and tg-ArcSwe transgenic mice. In this study, we aimed to identify which of these models were best suited to investigate pretargeted imaging approaches beyond the blood brain barrier. We evaluated this by pretargeted autoradiography using the Aβ-targeting antibody 3D6 and an
111
In-labeled Tz. Evaluation criteria were target-to-background ratios and accessibility. APP/PS1 mice showed Aβ accumulation in high and low binding brain regions and is as such less suitable for pretargeted purposes. 5xFAD and tg-ArcSwe mice showed similar uptake in high binding regions whereas low uptake in low binding regions and are better suited to evaluate pretargeted imaging approaches. 5xFAD mice are advantaged over tg-ArcSwe mice as pathology can be traced early (6 months compared to 18 months of age) and as 5xFAD mice are commercially available.
Importance In the context of emerging SARS-CoV-2 variants or lineages and new vaccines, it is key to accurately monitor COVID-19 vaccine effectiveness (CVE) to inform vaccination campaigns. Objective ...To estimate the effectiveness of COVID-19 vaccines administered in autumn and winter 2022 to 2023 against symptomatic SARS-CoV-2 infection (with all circulating viruses and XBB lineage in particular) among people aged 60 years or older in Europe, and to compare different CVE approaches across the exposed and reference groups used. Design, Setting, and Participants This case-control study obtained data from VEBIS (Vaccine Effectiveness, Burden and Impact Studies), a multicenter study that collects COVID-19 and influenza data from 11 European sites: Croatia; France; Germany; Hungary; Ireland; Portugal; the Netherlands; Romania; Spain, national; Spain, Navarre region; and Sweden. Participants were primary care patients aged 60 years or older with acute respiratory infection symptoms who were recruited at the 11 sites after the start of the COVID-19 vaccination campaign from September 2022 to August 2023. Cases and controls were defined as patients with positive and negative, respectively, reverse transcription–polymerase chain reaction (RT-PCR) test results. Exposures The exposure was COVID-19 vaccination. The exposure group consisted of patients who received a COVID-19 vaccine during the autumn and winter 2022 to 2023 vaccination campaign and 14 days or more before symptom onset. Reference group included patients who were not vaccinated during or in the 6 months before the 2022 to 2023 campaign (seasonal CVE), those who were never vaccinated (absolute CVE), and those who were vaccinated with at least the primary series 6 months or more before the campaign (relative CVE). For relative CVE of second boosters, patients receiving their second booster during the campaign were compared with those receiving 1 booster 6 months or more before the campaign. Main Outcomes and Measures The outcome was RT-PCR–confirmed, medically attended, symptomatic SARS-CoV-2 infection. Four CVE estimates were generated: seasonal, absolute, relative, and relative of second boosters. CVE was estimated using logistic regression, adjusting for study site, symptom onset date, age, chronic condition, and sex. Results A total of 9308 primary care patients were included, with 1687 cases (1035 females; median IQR age, 71 65-79 years) and 7621 controls (4619 females 61%; median IQR age, 71 65-78 years). Within 14 to 89 days after vaccination, seasonal CVE was 29% (95% CI, 14%-42%), absolute CVE was 39% (95% CI, 6%-60%), relative CVE was 31% (95% CI, 15% to 44%), and relative CVE of second boosters was 34% (95% CI, 18%-47%) against all SARS-CoV-2 variants. In the same interval, seasonal CVE was 44% (95% CI, −10% to 75%), absolute CVE was 52% (95% CI, −23% to 82%), relative CVE was 47% (95% CI, −8% to 77%), and relative CVE of second boosters was 46% (95% CI, −13% to 77%) during a period of high XBB circulation. Estimates decreased with time since vaccination, with no protection from 180 days after vaccination. Conclusions and Relevance In this case-control study among older Europeans, all CVE approaches suggested that COVID-19 vaccines administered in autumn and winter 2022 to 2023 offered at least 3 months of protection against symptomatic, medically attended, laboratory-confirmed SARS-CoV-2 infection. The effectiveness of new COVID-19 vaccines against emerging SARS-CoV-2 variants should be continually monitored using CVE seasonal approaches.
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