| 1. |
- Anderson, Jenna, et al.
(författare)
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Molecular Signatures of a TLR4 Agonist-Adjuvanted HIV-1 Vaccine Candidate in Humans
- 2018
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Systems biology approaches have recently provided new insights into the mechanisms of action of human vaccines and adjuvants. Here, we investigated early transcriptional signatures induced in whole blood of healthy subjects following vaccination with a recombinant HIV-1 envelope glycoprotein subunit CN54gp140 adjuvanted with the TLR4 agonist glucopyranosyl lipid adjuvant-aqueous formulation (GLA-AF) and correlated signatures to CN54gp140-specific serum antibody responses. Fourteen healthy volunteers aged 18-45 years were immunized intramuscularly three times at 1-month intervals and whole blood samples were collected at baseline, 6 h, and 1, 3, and 7 days post first immunization. Subtle changes in the transcriptomic profiles were observed following immunization, ranging from over 300 differentially expressed genes (DEGs) at day 1 to nearly 100 DEGs at day 7 following immunization. Functional pathway analysis revealed blood transcription modules (BTMs) related to general cell cycle activation, and innate immune cell activation at early time points, as well as BTMs related to T cells and B cell activation at the later time points post-immunization. Diverse CN54gp140-specific serum antibody responses of the subjects enabled their categorization into high or low responders, at early (< 1 month) and late (up to 6 months) time points post vaccination. BTM analyses revealed repression of modules enriched in NK cells, and the mitochondrial electron chain, in individuals with high or sustained antigen-specific antibody responses. However, low responders showed an enhancement of BTMs associated with enrichment in myeloid cells and monocytes as well as integrin cell surface interactions. Flow cytometry analysis of peripheral blood mononuclear cells obtained from the subjects revealed an enhanced frequency of CD56(dim) NK cells in the majority of vaccines 14 days after vaccination as compared with the baseline. These results emphasize the utility of a systems biology approach to enhance our understanding on the mechanisms of action of TLR4 adjuvanted human vaccines.
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| 2. |
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| 3. |
- Bahrami, F., et al.
(författare)
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Blood transcriptional profiles distinguish different clinical stages of cutaneous leishmaniasis in humans
- 2022
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Ingår i: Molecular Immunology. - : Elsevier BV. - 0161-5890. ; 149, s. 165-173
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Tidskriftsartikel (refereegranskat)abstract
- Cutaneous leishmaniasis (CL) is a neglected tropical disease with severe morbidity and socioeconomic sequelae. A better understanding of underlying immune mechanisms that lead to different clinical outcomes of CL could inform the rational design of intervention measures. While transcriptomic analyses of CL lesions were recently reported by us and others, there is a dearth of information on the expression of immune-related genes in the blood of CL patients. Herein, we investigated immune-related gene expression in whole blood samples collected from individuals with different clinical stages of CL along with healthy volunteers in an endemic CL region where Leishmania (L.) tropica is prevalent. Study participants were categorized into asymptomatic (LST+) and healthy uninfected (LST-) groups based on their leishmanin skin test (LST). Whole blood PAXgene samples were collected from volunteers, who had healed CL lesions, and patients with active L. tropica cutaneous lesions. Quality RNA extracted from 57 blood samples were subjected to Dual-color reverse-transcription multiplex ligation-dependent probe amplification (dcRT-MLPA) assay for profiling 144 immune-related genes. Results show significant changes in the expression of genes involved in interferon signaling pathway in the blood of active CL patients, asymptomatics and healed individuals. Nonetheless, distinct profiles for several immune-related genes were identified in the healed, the asymptomatic, and the CL patients compared to the healthy controls. Among others, IFI16 and CCL11 were found as immune transcript signatures for the healed and the asymptomatic individuals, respectively. These results warrant further exploration to pinpoint novel blood biomarkers for different clinical stages of CL.
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| 4. |
- Del Campo, Judith, et al.
(författare)
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Intranasal immunization with a proteoliposome-derived cochleate containing recombinant gD protein confers protective immunity against genital herpes in mice.
- 2010
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 28:5, s. 1193-200
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the potential of intranasal (IN) immunization with Neisseria meningitides B proteoliposome (AFPL1) and AFPL1-derived cochleate (AFCo1), containing glycoprotein D (gD) of herpes simplex virus type 2 (HSV-2) for induction of protective immunity against genital herpes infection in mice. We could show that IN immunization with both AFPL1 and AFCo1 containing gD induced gD-specific IgG antibody and lymphoproliferative responses. However, IFN-gamma response could only be detected in CD4(+) splenic cells and genital lymph node cells of the AFCo1gD immunized mice upon recall antigen stimulation in vitro. Importantly, IN immunization with AFCo1gD could elicit a complete protection against an otherwise lethal vaginal challenge with HSV-2, while the AFPL1gD immunized mice were only partially protected. Further, we could show that the IFN-gamma response and protective immunity observed after IN immunization with AFCo1gD are mediated via the adaptor molecule myeloid differentiation factor 88. These data may have implications for the development of a mucosal vaccine against genital herpes.
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| 5. |
- Khoomrung, Sakda, 1978, et al.
(författare)
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Metabolic Profiling and Compound-Class Identification Reveal Alterations in Serum Triglyceride Levels in Mice Immunized with Human Vaccine Adjuvant Alum
- 2020
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3907 .- 1535-3893. ; 19:1, s. 269-278
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Tidskriftsartikel (refereegranskat)abstract
- Alum has been widely used as an adjuvant for human vaccines; however, the impact of Alum on host metabolism remains largely unknown. Herein, we applied mass spectrometry (MS) (liquid chromatography-MS)-based metabolic and lipid profiling to monitor the effects of the Alum adjuvant on mouse serum at 6, 24, 72, and 168 h post-vaccination. We propose a new strategy termed subclass identification and annotation for metabolomics for class-wise identification of untargeted metabolomics data generated from high-resolution MS. Using this approach, we identified and validated the levels of several lipids in mouse serum that were significantly altered following Alum administration. These lipids showed a biphasic response even 168 h after vaccination. The majority of the lipids were triglycerides (TAGs), where TAGs with long-chain unsaturated fatty acids (FAs) decreased at 24 h and TAGs with short-chain FAs decreased at 168 h. To our knowledge, this is the first report on the impact of human vaccine adjuvant Alum on the host metabolome, which may provide new insights into the mechanism of action of Alum. ©
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| 6. |
- Labori, Frida, et al.
(författare)
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Clinical follow-up of left atrial appendage occlusion in patients with atrial fibrillation ineligible of oral anticoagulation treatment-a systematic review and meta-analysis
- 2021
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Ingår i: Journal of Interventional Cardiac Electrophysiology. - : Springer Science and Business Media LLC. - 1383-875X .- 1572-8595. ; 61:2, s. 215-225
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The recommended stroke prevention for patients with atrial fibrillation (AF) and increased risk of ischemic stroke is oral anticoagulation (OAC). Parts of the patient population are not eligible due to contraindication, and percutaneous left atrial occlusion (LAAO) can then be a preventive treatment option. The aim of this systematic review and meta-analysis is to estimate the long-term clinical effectiveness of LAAO as stroke prevention in patients with AF, increased risk of ischemic stroke, and contraindication to OAC. Methods We performed a systematic review and meta-analysis, using Poisson random effect models, to estimate the incidence rate (events per 100 patient-years) of ischemic stroke, transient ischemic attack, major bleeding, and all-cause death after LAAO treatment. We also calculated the risk reduction of ischemic stroke with LAAO compared with no stroke prevention estimated through a predicted risk in an untreated population (5.5 per 100 patient-years). Results We included 29 observational studies in our meta-analysis, including 7 951 individuals and 12 211 patient-years. The mean CHA(2)DS(2)-VASc score among the patients in the included studies is 4.32. The pooled incidence rate of ischemic stroke is 1.38 per 100 patient-years (95% CI 1.08; 1.77). According to a meta-regression model, the estimated incidence rate of ischemic stroke at CHA(2)DS(2)-VASc 4 is 1.39 per 100 patient-years. This implies a risk reduction of 74.7% with LAAO compared to predicated risk with no stroke prevention. Conclusions Our results suggest that LAAO is effective as stroke prevention for patients with AF, increased risk of stroke, and contraindication to oral anticoagulation.
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| 7. |
- Labori, Frida, et al.
(författare)
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Cost-effectiveness analysis of left atrial appendage occlusion in patients with atrial fibrillation and contraindication to oral anticoagulation.
- 2022
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 43:13, s. 1348-1356
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Tidskriftsartikel (refereegranskat)abstract
- This study aims to estimate the cost-effectiveness of percutaneous left atrial appendage occlusion (LAAO) compared to standard stroke prevention care for patients with atrial fibrillation (AF) and contraindication to oral anticoagulation (OAC) in a Swedish healthcare and public sector perspective.We used a combined decision tree and cohort Markov model to estimate costs and quality-adjusted life-years (QALYs) over a lifetime horizon with LAAO compared to standard of care where the treatment effect is based on a recent meta-analysis. According to our analysis, LAAO gives more QALYs than standard of care (7.11 vs. 6.12). Furthermore, LAAO treatment is related to the first-year cost of 14 984 Euro (EUR) and higher average healthcare costs over the lifetime by about 4010 EUR, which gives an incremental cost-effectiveness ratio of LAAO vs. standard of care at 4047 EUR per gained QALY. From a public sector perspective, LAAO reduces average costs due to substantial reductions in long-term care and, thus, implies that LAAO is dominant from a public sector perspective (lower average costs and better health outcomes).From both Swedish healthcare and public sector perspectives, LAAO can be considered cost-effective compared to standard of care for individuals with AF and contraindication to OAC. However, these results must be confirmed in health economic evaluations alongside the ongoing randomized clinical trials.Is left atrial appendage occlusion (LAAO) cost-effective for patients with atrial fibrillation (AF) and contraindication to oral anticoagulation (OAC) compared to the standard of care from a Swedish healthcare and public sector perspective?LAAO is associated with lower cost than the standard of care from a public sector perspective and an incremental cost of 4010 Euro from a healthcare perspective. Furthermore, LAAO is related to better health outcomes than the standard of care.Treatment with LAAO among individuals with AF and contraindication to OAC can be considered as cost-effective compared to the standard of care from a Swedish healthcare and public sector perspective.
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| 8. |
- Labori, Frida, et al.
(författare)
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Long-term effects on healthcare utilisation among spouses of persons with stroke.
- 2023
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Ingår i: BMC Health Services Research. - 1472-6963. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Stroke is a common and costly disease affecting the person with stroke and their relatives. If the negative effect on the health of informal caregivers to a person with stroke translates into an increased healthcare consumption has not yet been studied. Further, the importance of including costs and health consequences of informal caregiving in health economic evaluation supporting decision-making is an ongoing discussion. Therefore, this study aims to estimate the long-term effect on healthcare utilisation among spouses of persons with a first-ever stroke.The study population consists of spouses of persons with first-ever stroke events in 2010-2011 and a reference population matched on age, sex and municipality of residence. We have access to information on healthcare utilisation five years before and five years after the stroke event for the whole study population. Using a difference-in-difference approach, the main analysis estimates the effects on primary and specialist outpatient care visits and days with inpatient care per year. Further, we analyse the healthcare utilisation among spouses depending on the modified Rankin Scale (mRS) of the person with stroke.Our main analysis indicates that spouses have slightly more days with inpatient care five years after the stroke event than the reference population (p=0.03). In contrast, spouses have fewer primary and specialist outpatient care visits than the reference population following the stroke event. In the analysis where spouses' healthcare utilisation is analysed according to the mRS status of the person with stroke, we identify the most notable change in the number of visits to specialist outpatient and days with inpatient care among spouses of persons with mRS 3 (dependency in daily activities).Our study suggests that being the spouse of a person with stroke has minor effects on healthcare utilisation. Further, healthcare utilisation is most affected among the spouses of persons with stroke and dependency in daily activities (mRS 3). According to our results, it does not seem vital to include spouses of persons with stroke healthcare utilisation in health economic evaluations.
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| 9. |
- Labori, Frida, et al.
(författare)
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The impact of stroke on spousal and family income : a difference-in-difference study from Swedish national registries
- 2024
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Ingår i: Topics in Stroke Rehabilitation. - : Taylor & Francis. - 1074-9357 .- 1945-5119. ; 31:4, s. 381-389
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Tidskriftsartikel (refereegranskat)abstract
- AimTo investigates the financial consequences in the overall population spouses of persons with stroke in Sweden as well as for subgroups based on spouses age, sex and modified Rankin Scale (mRS) of the person with stroke.MethodsThe study population consists of spouses aged <= 60 during the year of their partner's stroke event. Each spouse was matched to four reference individuals. This longitudinal registry data covers spouses and a reference population between 2005 and 2016. We use difference-in-differences to estimate the impact on individual income from paid work, disposable individual income, and disposable family income.ResultsThe primary analysis shows a small and statistically insignificant decrease on spouses' individual income from paid work and disposable individual income. In the subgroup analysis based on mRS, the largest effect is seen in mRS 4-5, where spouses' individual income from paid work and disposable individual income increases after their partner's stroke. Further, younger female spouses' individual income from paid work decreases by 1 614 EUR (p = 0.008) on average.ConclusionThe financial consequences are small in the overall population of spouses. However, for some subgroups, younger women, and spouses of persons with stroke and mRS 4-5, the financial consequences are more prominent.
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| 10. |
- Lindqvist, Madelene, 1982, et al.
(författare)
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The mucosal adjuvant effect of alpha-galactosylceramide for induction of protective immunity to sexually transmitted viral infection.
- 2009
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 182:10, s. 6435-43
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Tidskriftsartikel (refereegranskat)abstract
- Development of mucosal adjuvants to generate immunity in the female genital tract may have important implications for the development of vaccines to counter sexually transmitted infections. alpha-Galactosylceramide (alpha-GalCer) is presented by CD1d molecule on APCs to invariant Valpha14(+) NKT (iNKT) cells, which upon activation rapidly produce large amounts of immunomodulatory cytokines, leading to activation of a variety of innate and adaptive immune cells. Here, we assessed whether alpha-GalCer could act as a mucosal adjuvant for induction of protective immunity against genital herpes. We found that intranasal immunization with HSV-2 glycoprotein D (gD) in combination with alpha-GalCer elicits strong systemic gD-specific IgG Ab response as well as lymphoproliferative response with a mixed Th1/Th2 cytokine profile in the spleen, mediastinal lymph nodes, and genital lymph nodes. Importantly, such an immunization scheme conferred complete protection against an otherwise lethal vaginal HSV-2 challenge. We could also show that intravaginal immunization with gD plus alpha-GalCer generates potent gD-specific lymphoproliferative and IFN-gamma responses in the genital lymph nodes and spleen. Furthermore, the vaginally immunized mice developed a strong systemic and mucosal IgG Ab response and protection against vaginal HSV-2 challenge. The mucosal adjuvant effect of alpha-GalCer was found to be mediated via CD1d molecule and appeared to be independent of the usage of the adaptor molecule MyD88. To our knowledge, this is the first report on the mucosal adjuvant effect of alpha-GalCer for induction of protective immunity against a sexually transmitted pathogen.
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