| 1. |
- Larsson, Simon, 1982, et al.
(författare)
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Contextualizing negative attitudes to wildlife and wildlife governance in the moral economy of Swedish farmers
- 2022
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Ingår i: Frontiers in Conservation Science. - : Frontiers Media SA. - 2673-611X. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Conflicts over managing large carnivores have been prominent in Sweden in recent decades. The most significant controversies are related to wolves, but the bear, lynx, and wolverine are also included. While the state and environmental organizations make efforts to guarantee a viable population of the large protected carnivores, farmers generally have a negative attitude towards large carnivores and a low level of trust in wildlife governance. Based on 22 in-depth interviews, 37 telephone questionnaires with Swedish farmers, and an analysis of 111 applications for protective hunting, this paper aims to demonstrate how these farmers’ perspectives on large carnivores can be explained by moral (sense of right and wrong) and moral economy (a system of obligations related to values and relations intervening with political views and financial decisions). The paper argues that farming, in addition to being an economic activity, is integrated with values, heritage, and relations to other human beings and animals. Farmers understand these values to be threatened by large carnivores, especially by wolves. The paper contextualizes negative sentiments, conflicts, protests, and also illegal hunting of large carnivores in relation to a sense of morals, sense of fairness, meanings, traditions, and mechanisms of daily life. We argue that this perspective provides a lens through which to interpret the conflict between farmers on the one side and the state and animal rights activists on the other. Such interpretation has consequences for understanding the legitimacy of government, shifting the focus from the processes of political governance (predominant in liberal political philosophy) to legitimacy tied to collective notions of social goods.
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| 2. |
- Bahnan, Wael, et al.
(författare)
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Spike-Dependent Opsonization Indicates Both Dose-Dependent Inhibition of Phagocytosis and That Non-Neutralizing Antibodies Can Confer Protection to SARS-CoV-2
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Spike-specific antibodies are central to effective COVID19 immunity. Research efforts have focused on antibodies that neutralize the ACE2-Spike interaction but not on non-neutralizing antibodies. Antibody-dependent phagocytosis is an immune mechanism enhanced by opsonization, where typically, more bound antibodies trigger a stronger phagocyte response. Here, we show that Spike-specific antibodies, dependent on concentration, can either enhance or reduce Spike-bead phagocytosis by monocytes independently of the antibody neutralization potential. Surprisingly, we find that both convalescent patient plasma and patient-derived monoclonal antibodies lead to maximum opsonization already at low levels of bound antibodies and is reduced as antibody binding to Spike protein increases. Moreover, we show that this Spike-dependent modulation of opsonization correlate with the outcome in an experimental SARS-CoV-2 infection model. These results suggest that the levels of anti-Spike antibodies could influence monocyte-mediated immune functions and propose that non-neutralizing antibodies could confer protection to SARS-CoV-2 infection by mediating phagocytosis.
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| 3. |
- Ghalwash, Mohamed, et al.
(författare)
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Islet autoantibody screening in at-risk adolescents to predict type 1 diabetes until young adulthood : a prospective cohort study
- 2023
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Ingår i: The Lancet Child and Adolescent Health. - 2352-4642. ; 7:4, s. 261-268
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Tidskriftsartikel (refereegranskat)abstract
- Background: Screening for islet autoantibodies in children and adolescents identifies individuals who will later develop type 1 diabetes, allowing patient and family education to prevent diabetic ketoacidosis at onset and to enable consideration of preventive therapies. We aimed to assess whether islet autoantibody screening is effective for predicting type 1 diabetes in adolescents aged 10−18 years with an increased risk of developing type 1 diabetes. Methods: Data were harmonised from prospective studies from Finland (the Diabetes Prediction and Prevention study), Germany (the BABYDIAB study), and the USA (Diabetes Autoimmunity Study in the Young and the Diabetes Evaluation in Washington study). Autoantibodies against insulin, glutamic acid decarboxylase, and insulinoma-associated protein 2 were measured at each follow-up visit. Children who were lost to follow-up or diagnosed with type 1 diabetes before 10 years of age were excluded. Inverse probability censoring weighting was used to include data from remaining participants. Sensitivity and the positive predictive value of these autoantibodies, tested at one or two ages, to predict type 1 diabetes by the age of 18 years were the main outcomes. Findings: Of 20 303 children with an increased type 1 diabetes risk, 8682 were included for the analysis with inverse probability censoring weighting. 1890 were followed up to 18 years of age or developed type 1 diabetes between the ages of 10 years and 18 years, and their median follow-up was 18·3 years (IQR 14·5–20·3). 442 (23·4%) of 1890 adolescents were positive for at least one islet autoantibody, and 262 (13·9%) developed type 1 diabetes. Time from seroconversion to diabetes diagnosis increased by 0·64 years (95% CI 0·34–0·95) for each 1-year increment of diagnosis age (Pearson's correlation coefficient 0·88, 95% CI 0·50–0·97, p=0·0020). The median interval between the last prediagnostic sample and diagnosis was 0·3 years (IQR 0·1–1·3) in the 227 participants who were autoantibody positive and 6·8 years (1·6–9·9) for the 35 who were autoantibody negative. Single screening at the age of 10 years was 90% (95% CI 86–95) sensitive, with a positive predictive value of 66% (60–72) for clinical diabetes. Screening at two ages (10 years and 14 years) increased sensitivity to 93% (95% CI 89–97) but lowered the positive predictive value to 55% (49–60). Interpretation: Screening of adolescents at risk for type 1 diabetes only once at 10 years of age for islet autoantibodies was highly effective to detect type 1 diabetes by the age of 18 years, which in turn could enable prevention of diabetic ketoacidosis and participation in secondary prevention trials. Funding: JDRF International.
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| 4. |
- Groß, Rüdiger, et al.
(författare)
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Macromolecular Viral Entry Inhibitors as Broad-Spectrum First-Line Antivirals with Activity against SARS-CoV-2
- 2022
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Ingår i: Advanced Science. - : Wiley. - 2198-3844. ; 9:20
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Tidskriftsartikel (refereegranskat)abstract
- Inhibitors of viral cell entry based on poly(styrene sulfonate) and its core–shell nanoformulations based on gold nanoparticles are investigated against a panel of viruses, including clinical isolates of SARS-CoV-2. Macromolecular inhibitors are shown to exhibit the highly sought-after broad-spectrum antiviral activity, which covers most analyzed enveloped viruses and all of the variants of concern for SARS-CoV-2 tested. The inhibitory activity is quantified in vitro in appropriate cell culture models and for respiratory viral pathogens (respiratory syncytial virus and SARS-CoV-2) in mice. Results of this study comprise a significant step along the translational path of macromolecular inhibitors of virus cell entry, specifically against enveloped respiratory viruses.
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| 5. |
- Hylander, Terese, et al.
(författare)
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Intralymphatic immunotherapy of pollen-induced rhinoconjunctivitis: a double-blind placebo-controlled trial.
- 2016
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Allergen-specific immunotherapy represents the only disease-modifying treatment for allergic diseases. We and others have previously demonstrated that intralymphatic immunotherapy (ILIT), a less time-consuming alternative to conventional subcutaneous immunotherapy (SCIT), is safe and effective. However, this has recently been disputed. The aim of this study was therefore to expand our previous trial, further assessing the safety and efficacy of ILIT.
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| 6. |
- Izadi, Arman, et al.
(författare)
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Subclass-switched anti-Spike IgG3 oligoclonal cocktails strongly enhance Fc-mediated opsonization
- 2023
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Ingår i: Proceedings of the National Academy of Sciences. - 1091-6490. ; 120:15
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Tidskriftsartikel (refereegranskat)abstract
- Antibodies play a central role in the immune defense against SARS-CoV-2. Emerging evidence has shown that nonneutralizing antibodies are important for immune defense through Fc-mediated effector functions. Antibody subclass is known to affect downstream Fc function. However, whether the antibody subclass plays a role in anti-SARS-CoV-2 immunity remains unclear. Here, we subclass-switched eight human IgG1 anti-spike monoclonal antibodies (mAbs) to the IgG3 subclass by exchanging their constant domains. The IgG3 mAbs exhibited altered avidities to the spike protein and more potent Fc-mediated phagocytosis and complement activation than their IgG1 counterparts. Moreover, combining mAbs into oligoclonal cocktails led to enhanced Fc- and complement receptor-mediated phagocytosis, superior to even the most potent single IgG3 mAb when compared at equivalent concentrations. Finally, in an in vivo model, we show that opsonic mAbs of both subclasses can be protective against a SARS-CoV-2 infection, despite the antibodies being nonneutralizing. Our results suggest that opsonic IgG3 oligoclonal cocktails are a promising idea to explore for therapy against SARS-CoV-2, its emerging variants, and potentially other viruses.
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| 7. |
- Larsson, Anthony, et al.
(författare)
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Welfare services in an era of digital disruption : How digitalization reshapes the health care market
- 2019. - 1st
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Ingår i: Digital Transformation and Public Services : Societal Impacts in Sweden and Beyond. - Oxon : Routledge. - 9780429319297 - 9780367333430 ; , s. 33-57
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Bokkapitel (refereegranskat)abstract
- This chapter examines public and private actors’ reactions to the emergent use of telemedicine on the Swedish primary health care market. The purpose is to investigate how the industry change, brought on by technological advancements, affects the actors’ perception of their roles in the market and, in particular, their roles in relation to each other. Data were collected through semi-structured interviews with representatives from the 1) public sector, 2) private telemedicine companies, and 3) private industry organizations. The results indicate that both the public and private sector anticipate telemedicine to carry a significant future impact on the health care market and its dynamics. Nevertheless, the perceived potential of influencing the new market frames differed between the different actors. The results also indicated that increased collaborative efforts can be expected to emerge due to the rise of telemedicine. Still, the different actors perceived various obstacles toward this development. The study concludes by suggesting several practical implications for the public as well as the private sector.
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| 8. |
- Larsson, Matilda, et al.
(författare)
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Melt processability and thermomechanical properties of blends based on polyhydroxyalkanoates and poly(butylene adipate-co-terephthalate)
- 2016
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Ingår i: RSC Advances. - 2046-2069. ; 6:50, s. 44354-44363
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Tidskriftsartikel (refereegranskat)abstract
- The limited thermal stability of polyhydroxyalkanoates (PHAs) hinders their wide applicability, and methods to improve the processability of these biopolyesters are needed for efficient processing, e.g. by melt extrusion. In the present study we have shown by isothermal gravimetry, dynamic rheology and molecular weight analysis that the thermal stability of the PHAs at the processing temperature can be dramatically improved by simply washing the materials in a 1 mM aqueous HCl solution. Hence, the thermal decomposition temperature increased by up to 50 °C after the treatment. Subsequently, treated poly(3-hydroxybutyrate) and poly(3-hydroxybutyrate-co-4-hydroxybutyrate) were blended with different amounts of poly(butylene adipate-co-terephthalate) by melt extrusion in order to further enhance the processability and thermomechanical properties. Microscopy of freeze fractured samples of the biodegradable blends showed phase separated blends with poor interfacial adhesion. Melt rheology and dynamic mechanical analysis results indicated a phase inversion between 60 and 80 wt% of the respective PHA. After adding dicumyl peroxide during the extrusion, the interfacial adhesion improved significantly, and the dynamic shear and tensile storage modulii increased with increasing content of the peroxide. The results of the present study demonstrate that an acid wash may significantly improve processability of PHAs, and that combinations of blending and reactive extrusion can be employed to further enhance and tune the thermomechanical properties of the materials.
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| 9. |
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| 10. |
- Larsson, Olivia, et al.
(författare)
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Novel strategies for the treatment of grass pollen-induced allergic rhinitis
- 2016
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Ingår i: Expert Opinion on Biological Therapy. - : Informa UK Limited. - 1471-2598 .- 1744-7682. ; 16:9, s. 1143-1150
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Allergic rhinitis (AR) affects over 20% of the population of Europe and the United States. Allergen immunotherapy (AIT) is currently the only form of treatment that affects symptoms and modifies the progression of disease. Established forms of AIT include subcutaneous (SCIT) and sublingual (SLIT) immunotherapy and are widely effective, yet only 2-9% of eligible patients undergo therapy, likely due to the long duration of treatment. As a result, novel, faster forms of AIT are currently under development. Areas covered: This article provides an overview of AR and summarises the efficacy and mechanisms of established forms of AIT, highlighting the current drawbacks. We discuss novel strategies of AIT that have been developed in an attempt to tackle these limitations, including epicutaneous, intradermal and intralymphatic immunotherapy (ILIT), focusing on ILIT, the treatment that has been most comprehensively assessed. Expert opinion: Current strategies to treat AR suffer from a poor safety profile and, importantly, lack of adherence. ILIT is a faster and safer form of AIT, with a treatment regime of only 12 weeks. Further validation is required, but ILIT, with its short and comparatively inexpensive protocol, has the potential to offer disease-modifying therapy to a larger number of patients.
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| 11. |
- Larsson, Olivia, et al.
(författare)
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Substance P represents a novel first-line defense mechanism in the nose
- 2018
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 141:1, s. 3-136
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neuropeptides, such as substance P (SP), have long been seen as mediators of widespread continuous airway inflammation, a process known as neurogenic inflammation. However, this has been difficult to demonstrate clinically, suggesting an alternative role for these signaling molecules. Objectives: We sought to examine the role of SP in nasal infection by assessing the release of SP in response to viral stimulation and characterizing the effects of SP on innate immunity, with the latter reflected in changes in local Toll-like receptor (TLR) expression. Methods: The distribution of SP and TLRs in the nasal mucosa and local airway neurons was assessed with immunohistochemistry. The TLR7 agonists R-837 and R-848 were used to mimic a viral insult in the upper airways represented by primary human nasal epithelial cells (HNECs) and murine nasal epithelial cells (MNECs) and isolated murine trigeminal ganglial neurons. SP release from HNECs, MNECs, and trigeminal ganglial neurons was quantified with EIA. The effects of SP on TLR expression on HNECs were determined by using flow cytometry and confocal microscopy. Results: SP was released from the sensory neurons, MNECs, and HNECs within 15 minutes of local TLR7 stimulation. Subsequently, stimulation with SP induced upregulation of TLR expression in HNECs within 30 minutes through induction of TLR movement within HNECs. Upregulation of TLR expression was not evident when cells were treated with the neurokinin 1 receptor antagonist aprepitant before SP stimulation. Conclusions: This highlights a novel role for sensory neuropeptides as acute and local mediators of pathogen-driven inflammation, rapidly priming innate immune defenses in the airway.
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| 12. |
- Larsson, Olivia, et al.
(författare)
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The SP‐TLR axis, which locally primes the nasal mucosa, is impeded in patients with allergic rhinitis
- 2021
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Ingår i: Clinical and Translational Allergy. - Oxford, United kingdom : John Wiley & Sons. - 2045-7022. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSubstance P (SP) and toll-like receptors (TLRs) contribute to airway disease, particularly during viral infection. We recently demonstrated that SP can act as an initial response to viral stimuli in the upper airway by upregulating TLRs in the nasal epithelia (the SP-TLR axis). Patients with allergic rhinitis (AR) suffer from prolonged airway infections. The aim of the present study was to examine if patients with AR exhibit a disturbance in the SP-TLR axis.MethodHuman nasal biopsies and human nasal epithelial cells (HNEC) from healthy volunteers and patients with AR were cultured in the presence of SP. Epithelial expression of TLR4, neutral endopeptidase (NEP) and neurokinin 1 (NK1) were evaluated with flow cytometry and/or quantitative polymerase chain reaction after 30 min to 24 h. The effect of SP on nasal lipopolysaccharide-induced interleukin-8 (IL-8) release was investigated.ResultsSP stimulation of tissue from healthy volunteers resulted in a transient increase of the TLR4 expression, whereas stimulation of AR patient-derived material led to a delayed and prolonged upregulation of TLR4. NEP expression in HNEC was lower in AR than healthy controls whereas NK1 receptor expression was increased. SP pretreatment increased TLR4-dependent IL-8 expression in healthy controls, but not in AR.ConclusionsSP-induced regulation of TLR4 in the human nasal mucosa is disturbed in AR. An altered SP-mediated innate immune response may contribute to the dysfunctional and often prolonged responses to infection in AR.
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| 13. |
- Le Moëne, Olivia, et al.
(författare)
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A New Tool for Quantifying Mouse Facial Expressions
- 2023
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Ingår i: eNeuro. - : SOC NEUROSCIENCE. - 2373-2822. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Facial expressions are an increasingly used tool to assess emotional experience and affective state during ex-perimental procedures in animal models. Previous studies have successfully related specific facial features with different positive and negative valence situations, most notably in relation to pain. However, characteriz-ing and interpreting such expressions remains a major challenge. We identified seven easily visualizable facial parameters on mouse profiles, accounting for changes in eye, ear, mouth, snout and face orientation. We monitored their relative position on the face across time and throughout sequences of positive and aversive gustatory and somatosensory stimuli in freely moving mice. Facial parameters successfully captured response profiles to each stimulus and reflected spontaneous movements in response to stimulus valence, as well as contextual elements such as habituation. Notably, eye opening was increased by palatable tastants and innoc-uous touch, while this parameter was reduced by tasting a bitter solution and by painful stimuli. Mouse ear posture appears to convey a large part of emotional information. Facial expressions accurately depicted wel-fare and affective state in a time-sensitive manner, successfully correlating time-dependent stimulation. This study is the first to delineate rodent facial expression features in multiple positive valence situations, including in relation to affective touch. We suggest using this facial expression assay might provide mechanistic insights into emotional expression and improve the translational value of experimental studies in rodents on pain and other states.
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| 14. |
- Mannerkorpi, Kaisa, 1955, et al.
(författare)
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Acute effects of physical exercise on the serum insulin-like growth factor system in women with fibromyalgia
- 2017
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 The Author(s).Background: Increased Serum insulin-like growth factor-1 (S-IGF-1) has been noted after physical activity in healthy subjects, while the acute release of S-IGF-1 in relation to exercise has not previously been studied in women with fibromyalgia (FM). S-IGF-1 and its binding protein (S-IGFBP-3) are mediated by growth hormone and have anabolic effects on the skeletal muscle. Aim of the study was to investigate acute release of IGF-1 after aerobic exercise in women with FM. Methods: The acute effect of physical exercise on S-IGF-1 and S-IGFBP-3 were studied in 22 women with FM and in 27 healthy controls during moderate and high-intensity cycling (i.e. ratings 12-13 and 15-17, on Borg's perceived exertion scale (RPE), respectively). Self-reported pain and fatigue were recorded. Differences within and between the two groups were analyzed. Results: After 15 min of bicycling, S-IGF-1 and S-IGFBP-3 increased both within the group with FM and in the healthy controls (p < 0.01). The increases in S-IGF-1 did not significantly differ between the women with FM and the healthy control group (mean increase 11 ± 10 vs. 11 ± 15 ng/ml and 13 ± 10 vs. 19 ± 22 ng/ml) when bicycling at moderate or high intensity, respectively. Self-reported pain and fatigue during exercise, irrespective of intensity, were higher in women with FM compared with healthy controls (p < 0.001). Conclusions: Fifteen minutes bicycling at moderate intensity was sufficient to acutely mobilise S-IGF-1 in women with FM similarly to healthy controls in spite of higher score of fatigue and pain in women with FM. Hence, patients with FM were able to activate their skeletal muscle metabolism during a short, moderate bout of exercise and were not resistant to training effects. The result is important for encouraging clinical rehabilitation of patients with FM who commonly exercise at a moderate, rather than at a high-intensity level. Trial registration: ClinicalTrials.govNCT01592916, May 4, 2012.
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| 15. |
- Middha, Pooja K., et al.
(författare)
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A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry
- 2023
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Ingår i: Breast Cancer Research. - : BioMed Central (BMC). - 1465-5411 .- 1465-542X. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Genome-wide studies of gene-environment interactions (GxE) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide GxE analysis of similar to 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 x 10(-5) prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94). Conclusions Overall, the contribution of GxE interactions to the heritability of breast cancer is very small. At the population level, multiplicative GxE interactions do not make an important contribution to risk prediction in breast cancer.
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| 16. |
- Mousa, Maryam, et al.
(författare)
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Branched polyesters from radical ring-opening polymerization of cyclic ketene acetals : synthesis, chemical hydrolysis and biodegradation
- 2023
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Ingår i: Polymer Chemistry. - 1759-9954 .- 1759-9962. ; 14:47, s. 5154-5165
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Tidskriftsartikel (refereegranskat)abstract
- Herein, we report a new synthetic route to the cyclic ketene acetal, 2-methylene-4-methyl-1,3-dioxepane (Me-MDO) as a way to expand the tool box of synthesis procedures for cyclic ketene acetals and actualize them as realistic alternatives for synthesizing biodegradable polymers. In this work, 2-methylene-1,3-dioxepane (MDO) and Me-MDO were polymerized by radical ring-opening polymerization to synthesize degradable polyesters. NMR and SEC were used to monitor the polymerization while DSC was used to study the thermal properties. Poly(2-methylene-1,3-dioxepane) (PMDO) showed increased degree of branching with higher conversion, subsequently decreasing crystallinity. The effect of branching and the introduction of side-groups on the chemical hydrolysis rate and biodegradability of the polyesters was assessed using a chemical hydrolysis test and the OECD 301D ready biodegradability screening test, respectively. A significant reduction in the chemical hydrolysis rate and biodegradability was observed upon the introduction of a side group in the poly(2-methylene-4-methyl-1,3-dioxepane) (PMe-MDO) polyester. Less obvious effects on the hydrolysis rate and biodegradability were observed as a result of the polyester branching.
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| 17. |
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| 18. |
- Tran, Pham Tue Hung, 1991-, et al.
(författare)
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Development of a Multivalent Kunjin Virus Reporter Virus-Like Particle System Inducing Seroconversion for Ebola and West Nile Virus Proteins in Mice
- 2020
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Ingår i: Microorganisms. - Basel, Switzerland : MDPI. - 2076-2607. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- Kunjin virus (KUNV) is an attenuated strain of the severe neurotropic West Nile virus (WNV). The virus has a single-strand positive-sense RNA genome that encodes a polyprotein. Following gene expression, the polyprotein is cleaved into structural proteins for viral packaging and nonstructural proteins for viral replication and expression. Removal of the structural genes generate subgenomic replicons that maintain replication capacity. Co-expression of these replicons with the viral structural genes produces reporter virus-like particles (RVPs) which infect cells in a single round. In this study, we aimed to develop a system to generate multivalent RVPs based on KUNV to elicit an immune response against different viruses. We selected the Ebola virus (EBOV) glycoprotein (GP) and the matrix protein (VP40) genes, as candidates to be delivered by KUNV RVPs. Initially, we enhanced the production of KUNV RVPs by generating a stable cell line expressing the KUNV packaging system comprising capsid, precursor membrane, and envelope. Transfection of the DNA-based KUNV replicon into this cell line resulted in an enhanced RVP production. The replicon was expressed in the stable cell line to produce the RVPs that allowed the delivery of EBOV GP and VP40 genes into other cells. Finally, we immunized BALB/cN mice with RVPs, resulting in seroconversion for EBOV GP, EBOV VP40, WNV nonstructural protein 1, and WNV E protein. Thus, our study shows that KUNV RVPs may function as a WNV vaccine candidate and RVPs can be used as a gene delivery system in the development of future EBOV vaccines.
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| 19. |
- Tran, Pham Tue Hung, 1991-, et al.
(författare)
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Enhanced Seroconversion to West Nile Virus Proteins in Mice by West Nile Kunjin Replicon Virus-like Particles Expressing Glycoproteins from Crimean-Congo Hemorrhagic Fever Virus
- 2022
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Ingår i: Pathogens. - : MDPI. - 2076-0817. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Removal of genes coding for major parts of capsid (C), premembrane (prM), and envelope (E) proteins on the flavivirus genome aborts the production of infectious virus particles where the remaining genome forms a replicon that retains replicability in host cells. The C-prM-E proteins can also be expressed in trans with the flavivirus replicons to generate single-round infectious replicon virus-like particles (RVPs). In this study, we characterized the use of RVPs based on the Kunjin strain of WNV (WNVKUN) as a putative WNV vaccine candidate. In addition, the WNVKUN C-prM-E genes were substituted with the Crimean-Congo hemorrhagic fever virus (CCHFV) genes encoding the glycoproteins Gn and Gc to generate a WNVKUN replicon expressing the CCHFV proteins. To generate RVPs, the WNVKUN replicon was transfected into a cell line expressing the WNVKUN C-prM-E. Using immunoblotting and immunofluorescence assays, we showed that the replicon can express the CCHFV Gn and Gc proteins and the RVPs can transduce cells to express WNVKUN proteins and the CCHFV Gn and Gc proteins. Our study also revealed that these RVPs have potential as a vaccine platform with low risk of recombination as it infects cells only in one cycle. The immunization of mice with the RVPs resulted in high seroconversion to both WNV E and NS1 but limited seroconversion to CCHFV Gn and Gc proteins. Interestingly, we found that there was enhanced production of WNV E, NS1 antibodies, and neutralizing antibodies by the inclusion of CCHFV Gc and Gn into WNVKUN RVPs. Thus, this study indicates a complementary effect of the CCHFV Gn and Gc proteins on the immunogenicity by WNVKUN RVPs, which may be applied to develop a future vaccine against the WNV.
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| 20. |
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| 21. |
- Wille, Michelle, et al.
(författare)
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Temporal dynamics, diversity, and interplay in three components of the virodiversity of a Mallard population : Influenza A virus, avian paramyxovirus and avian coronavirus
- 2015
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Ingår i: Infection, Genetics and Evolution. - : Elsevier BV. - 1567-1348 .- 1567-7257. ; 29, s. 129-137
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Tidskriftsartikel (refereegranskat)abstract
- Multiple infections, or simultaneous infection of a host with multiple parasites, are the rule rather than the exception. Interactions between co-occurring pathogens in a population may be mutualistic, competitive or facilitative. For some pathogen combinations, these interrelated effects will have epidemiological consequences; however this is as yet poorly incorporated into practical disease ecology. For example, screening of Mallards for influenza A viruses (IAV) have repeatedly revealed high prevalence and large subtype diversity in the Northern Hemisphere. Other studies have identified avian paramyxovirus type 1 (APMV-1) and coronaviruses (CoVs) in Mallards, but without making inferences on the larger viral assemblage. In this study we followed 144 wild Mallards across an autumn season in a natural stopover site and constructed infection histories of IAV, APMV-1 and CoV. There was a high prevalence of IAV, comprising of 27 subtype combinations, while APMV-1 had a comparatively low prevalence (with a peak of 2%) and limited strain variation, similar to previous findings. Avian CoVs were common, with prevalence up to 12%, and sequence analysis identified different putative genetic lineages. An investigation of the dynamics of co-infections revealed a synergistic effect between CoV and IAV, whereby Coy prevalence was higher given that the birds were co-infected with IAV. There were no interactive effects between IAV and APMV-1. Disease dynamics are the result of an interplay between parasites, host immune responses, and resources; and is imperative that we begin to include all factors to better understand infectious disease risk. (C) 2014 Elsevier B.V. All rights reserved.
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| 22. |
- Yan, Jingyi, et al.
(författare)
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Distinct roles of vaccine-induced SARS-CoV-2-specific neutralizing antibodies and T cells in protection and disease
- 2024
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Ingår i: Molecular Therapy. - : Elsevier BV. - 1525-0016 .- 1525-0024. ; 32:2, s. 540-555
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-specific neutralizing antibodies (NAbs) lack cross-reactivity between SARS-CoV species and variants and fail to mediate long-term protection against infection. The maintained protection against severe disease and death by vaccination suggests a role for cross-reactive T cells. We generated vaccines containing sequences from the spike or receptor binding domain, the membrane and/or nucleoprotein that induced only T cells, or T cells and NAbs, to understand their individual roles. In three models with homologous or heterologous challenge, high levels of vaccine-induced SARS-CoV-2 NAbs protected against neither infection nor mild histological disease but conferred rapid viral control limiting the histological damage. With no or low levels of NAbs, vaccine-primed T cells, in mice mainly CD8+ T cells, partially controlled viral replication and promoted NAb recall responses. T cells failed to protect against histological damage, presumably because of viral spread and subsequent T cell-mediated killing. Neither vaccine- nor infection-induced NAbs seem to provide long-lasting protective immunity against SARS-CoV-2. Thus, a more realistic approach for universal SARS-CoV-2 vaccines should be to aim for broadly cross-reactive NAbs in combination with long-lasting highly cross-reactive T cells. Long-lived cross-reactive T cells are likely key to prevent severe disease and fatalities during current and future pandemics.
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