| 1. |
- Bråve, Andreas, et al.
(författare)
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Intranasal immunization of young mice with a multigene HIV-1 vaccine in combination with the N3 adjuvant induces mucosal and systemic immune responses
- 2008
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 26:40, s. 5075-5078
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Tidskriftsartikel (refereegranskat)abstract
- One of the major challenges for the development of an HIV vaccine is to induce potent virus-specific immune responses at the mucosal surfaces where transmission of virus occurs. Intranasal delivery of classical vaccines has been shown to induce good mucosal antibody responses, but so far for genetic vaccines the success has been limited. This study shows that young individuals are sensitive to nasal immunization with a genetic vaccine delivered in a formulation of a lipid adjuvant, the Eurocine N3. Intranasal delivery of a multiclade/multigene HIV-1 genetic vaccine gave rise to vaginal and rectal IgA responses as well as systemic humoral and cellular responses. As electroporation might become the preferred means of delivering genetic vaccines for systemic HIV immunity, nasal delivery by droplet formulation in a lipid adjuvant might become a means of priming or boosting the mucosal immunity. © 2008 Elsevier Ltd. All rights reserved.
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| 2. |
- Haroun-Izquierdo, Alvaro, et al.
(författare)
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Adaptive single-KIR(+)NKG2C(+) NK cells expanded from select superdonors show potent missing-self reactivity and efficiently control HLA-mismatched acute myeloid leukemia
- 2022
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Ingår i: Journal for ImmunoTherapy of Cancer. - : BMJ. - 2051-1426. ; 10:11, s. e005577-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundNatural killer (NK) cells hold great promise as a source for allogeneic cell therapy against hematological malignancies, including acute myeloid leukemia (AML). Current treatments are hampered by variability in NK cell subset responses, a limitation which could be circumvented by specific expansion of highly potent single killer immunoglobulin-like receptor (KIR)(+)NKG2C(+) adaptive NK cells to maximize missing-self reactivity.MethodsWe developed a GMP-compliant protocol to expand adaptive NK cells from cryopreserved cells derived from select third-party superdonors, that is, donors harboring large adaptive NK cell subsets with desired KIR specificities at baseline. We studied the adaptive state of the cell product (ADAPT-NK) by flow cytometry and mass cytometry as well as cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq). We investigated the functional responses of ADAPT-NK cells against a wide range of tumor target cell lines and primary AML samples using flow cytometry and IncuCyte as well as in a mouse model of AML.ResultsADAPT-NK cells were >90% pure with a homogeneous expression of a single self-HLA specific KIR and expanded a median of 470-fold. The ADAPT-NK cells largely retained their adaptive transcriptional signature with activation of effector programs without signs of exhaustion. ADAPT-NK cells showed high degranulation capacity and efficient killing of HLA-C/KIR mismatched tumor cell lines as well as primary leukemic blasts from AML patients. Finally, the expanded adaptive NK cells had preserved robust antibody-dependent cellular cytotoxicity potential and combination of ADAPT-NK cells with an anti-CD16/IL-15/anti-CD33 tri-specific engager led to near-complete killing of resistant CD45(dim) blast subtypes.ConclusionsThese preclinical data demonstrate the feasibility of off-the-shelf therapy with a non-engineered, yet highly specific, NK cell population with full missing-self recognition capability.
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| 3. |
- Henriksson, Pontus, et al.
(författare)
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A Smartphone App to Promote Healthy Weight Gain, Diet, and Physical Activity During Pregnancy (HealthyMoms) : Protocol for a Randomized Controlled Trial
- 2019
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Ingår i: JMIR Research Protocols. - : JMIR Publications Inc.. - 1929-0748. ; 8:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Excessive gestational weight gain is common and associated with adverse outcomes both in the short and long term. Although traditional lifestyle-based interventions have shown to mitigate excess gestational weight gain, little is known about whether mobile Health (mHealth) apps can promote healthy weight gain, diet, and physical activity during pregnancy.OBJECTIVE: The primary aim of the HealthyMoms trial is to determine the effectiveness of a smartphone app (HealthyMoms) for mitigating excess gestational weight gain during pregnancy. Secondary aims are to determine the effectiveness of the app on dietary habits, physical activity, body fatness, and glycemia during pregnancy.METHODS: HealthyMoms is a two-arm randomized controlled trial. Women are being recruited at routine visits at the maternity clinics in Linköping, Norrköping and Motala, Sweden. Women are randomized to the control or intervention group (n=150 per group). All women will receive standard care, and women in the intervention group will also receive the HealthyMoms smartphone app.RESULTS: Recruitment of participants to the trial was initiated in October 2017, and 190 women have so far completed the baseline measurement. The baseline measures are estimated to be finalized in December 2019, and the follow-up measures are estimated to be completed in June 2020.CONCLUSIONS: This project will evaluate a novel smartphone app intervention integrated with existing maternity health care. If successful, it has great potential to be implemented nationally in order to promote healthy weight gain and health behaviors during pregnancy.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13011.
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| 4. |
- Henriksson, Pontus, et al.
(författare)
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Associations of body composition and physical fitness with gestational diabetes and cardiovascular health in pregnancy : Results from the HealthyMoms trial
- 2021
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Ingår i: Nutrition & Diabetes. - : SPRINGERNATURE. - 2044-4052 .- 2044-4052. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to examine associations of body composition (fat mass index, % fat mass, fat-free mass index, body mass index) and physical fitness (cardiorespiratory fitness and handgrip strength) with gestational diabetes and cardiovascular health in early pregnancy. This cross-sectional study utilized baseline data (n = 303) collected in early pregnancy from the HealthyMoms trial. Body composition was measured using air-displacement plethysmography, cardiorespiratory fitness was assessed by means of the 6-min walk test and handgrip strength using a dynamometer. Logistic regression was used to estimate odds ratios (ORs) for gestational diabetes as well as high (defined as 1 SD above the mean) blood pressure, homeostatic model assessment for insulin resistance (HOMA-IR), and metabolic syndrome score (MetS score) per 1 SD increase in body composition and fitness variables. Fat mass index, % fat mass and body mass index were all strongly associated with gestational diabetes (ORs: 1.72-2.14, P <= 0.003), HOMA-IR (ORs: 3.01-3.80, P < 0.001), blood pressure (ORs: 1.81-2.05, P < 0.001) and MetS score (ORs: 3.29-3.71, P < 0.001). Associations with fat-free mass index were considerably weaker (ORs: 1.26-1.82, P = 0.001-0.15) and were strongly attenuated after adjustments for fat mass index (ORs: 0.88-1.54, P = 0.039-0.68). Finally, greater cardiorespiratory fitness was associated with lower risk of high HOMA-IR and MetS score (ORs: 0.57-0.63, P <= 0.004) although these associations were attenuated when accounting for fat mass index (ORs: 1.08-1.11, P >= 0.61). In conclusion, accurately measured fat mass index or % fat mass were strongly associated with gestational diabetes risk and markers of cardiovascular health although associations were not stronger than the corresponding ones for body mass index. Fat-free mass index had only weak associations with gestational diabetes and cardiovascular health which support that the focus during clinical care would be on excess fat mass and not fat-free mass.
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| 5. |
- Henriksson, Pontus, et al.
(författare)
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Body mass index and gestational weight gain in migrant women by birth regions compared with Swedish-born women : A registry linkage study of 0.5 million pregnancies
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:10
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Women migrating to high-income countries may have increased risks of adverse pregnancy outcomes as compared with native-born women. However, little is known whether migrant women are more likely to have unhealthy body mass index (BMI) or gestational weight gain (GWG), which is of importance considering the well-established links between unhealthy BMI and GWG with adverse pregnancy outcomes. Hence, the aim of the study was to examine the prevalence and estimate odds ratios (ORs) of underweight and obesity in the first trimester as well as inadequate and excessive GWG across birth regions in migrant (first-generation) and Swedish-born women in a population-based sample of pregnant women in Sweden.METHODS: This population-based study included 535 609 pregnancies from the Swedish Pregnancy Register between the years 2010-2018. This register has a coverage of approximately 90% and includes data on body weight, height, birth country and educational attainment. BMI in the first trimester of pregnancy was classified as underweight, normal weight, overweight and obesity whereas GWG was classified as inadequate, adequate and excessive according to the recommendations from the National Academy of Medicine, USA. BMI and GWG were examined according to 7 birth regions and the 100 individual birth countries. Adjusted ORs of underweight, obesity as well as inadequate or excessive GWG by birth regions were estimated using multinomial logistic regression.RESULTS: There were large disparities in unhealthy BMI and GWG across birth regions. For instance, women born in North Africa and Middle East and Sub-Saharan Africa had 1.40 (95% CI 1.35-1.44) and 2.13 (95% CI 2.03-2.23) higher odds of obesity compared with women born in Sweden. However, women born in Sub-Saharan Africa had also considerably higher odds of underweight (OR, 2.93 [95% CI 2.70-3.18]) and inadequate GWG (OR, 1.97 [95% CI 1.87-2.07]). The limitations of the study include the lack of a validated measure of acculturation and that the study only had data on first-generation migration.CONCLUSIONS: The large differences across the 7 regions and 100 countries highlights the importance of considering birth region and country-specific risks of unhealthy BMI and GWG in first-generation migrant women. Furthermore, inadequate GWG was common among pregnant first-generation migrant women, especially in women born in Sub-Saharan Africa, which demonstrates the need to promote adequate GWG, not only the avoidance of excessive GWG. Thus, our findings also indicate that additional support and interventions may be needed for first-generation migrant women from certain birth regions and countries in order to tackle the observed disparities in unhealthy BMI and GWG. Although further studies are needed, our results are useful for identifying groups of women at increased risk of unhealthy BMI and weight gain during pregnancy.
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| 6. |
- Henriksson, Pontus, et al.
(författare)
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Self-Rated Health in Migrant and Non-Migrant Women before, during and after Pregnancy : A Population-Based Study of 0.5 Million Pregnancies from the Swedish Pregnancy Register
- 2020
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Self-rated health is a strong health marker. Migrants have been suggested to have poorer self-rated health than non-migrants (i.e., native-born). However, little is known about whether there are disparities in self-reported health in relation to pregnancy. Therefore, the aim of the current study was to examine the odds of poor self-rated health before, during and after pregnancy in migrant women as compared to women born in Sweden. We utilized population-based data from the Swedish Pregnancy Register containing 0.5 million women born in Sweden (i.e., non-migrant women) and migrant women between 2010 and 2018. Self-rated health was reported on a 5-point scale (from very poor to very good). Very poor and poor health were categorized as poor self-rated health. Logistic regression was utilized to calculate odds ratios (ORs) that were unadjusted and adjusted for covariates (age, parity, educational attainment and body mass index). The results demonstrate disparities in self-rated health across birth regions. In comparison to women born in Sweden, women born in Latin America and the Caribbean, South Asia as well as North Africa and the Middle East had consistently higher odds of poor self-rated health before, during and after pregnancy (ORs ranging from 1.14 to 1.96 in both unadjusted and adjusted models). Although women born in Sub-Saharan Africa did have comparable self-rated health as to women born in Sweden before pregnancy, after accounting for covariates, they had lower odds of poor self-rated health during and after pregnancy (ORs: 0.71 and 0.80 respectively). Therefore, additional measures and support may be needed to tackle disparities in health between migrant and non-migrant women before, during and after pregnancy.
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| 7. |
- Jungebluth, Philipp, et al.
(författare)
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Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite : a proof-of-concept study
- 2011
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 378:9808, s. 1997-2004
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Tidskriftsartikel (refereegranskat)abstract
- Background Tracheal tumours can be surgically resected but most are an inoperable size at the time of diagnosis; therefore, new therapeutic options are needed. We report the clinical transplantation of the tracheobronchial airway with a stem-cell-seeded bioartificial nanocomposite. Methods A 36-year-old male patient, previously treated with debulking surgery and radiation therapy, presented with recurrent primary cancer of the distal trachea and main bronchi. After complete tumour resection, the airway was replaced with a tailored bioartificial nanocomposite previously seeded with autologous bone-marrow mononuclear cells via a bioreactor for 36 h. Postoperative granulocyte colony-stimulating factor filgrastim (10 mu g/kg) and epoetin beta (40 000 UI) were given over 14 days. We undertook flow cytometry, scanning electron microscopy, confocal microscopy epigenetics, multiplex, miRNA, and gene expression analyses. Findings We noted an extracellular matrix-like coating and proliferating cells including a CD105+ subpopulation in the scaffold after the reseeding and bioreactor process. There were no major complications, and the patient was asymptomatic and tumour free 5 months after trans plantation. The bioartificial nanocomposite has patent anastomoses, lined with a vascularised neomucosa, and was partly covered by nearly healthy epithelium. Post-operatively, we detected a mobilisation of peripheral cells displaying increased mesenchymal stromal cell phenotype, and upregulation of epoetin receptors, antiapoptotic genes, and miR-34 and miR-449 biomarkers. These findings, together with increased levels of regenerative-associated plasma factors, strongly suggest stem-cell homing and cell-mediated wound repair, extracellular matrix remodelling, and neovascularisation of the graft. Interpretation Tailor-made bioartificial scaffolds can be used to replace complex airway defects. The bioreactor reseeding process and pharmacological-induced site-specific and graft-specific regeneration and tissue protection are key factors for successful clinical outcome.
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| 8. |
- Lahtinen, Mika, et al.
(författare)
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In vivo h-VEGF(165) gene transfer improves early endothelialisation and patency in synthetic vascular grafts
- 2007
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Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 31:3, s. 383-390
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Small-diameter synthetic vascular graft performance is inferior to autologous vein grafts. This study tested the hypotheses that local in vivo administration of plasmids encoding for human vascular endothelial. growth factor (VEGF), or co-administration of plasmids encoding for human vascular endothelial growth factor/plasmids encoding for fibroblast growth factor-2 in the tissues surrounding a porous synthetic vascular graft would enhance graft endothelialisation and, consecutively, graft patency. Methods: First, optimal gene for small-diameter synthetic graft endothelialisation was studied in rat abdominal aorta model (n = 132): plasmids encoding for human vascular endothelial growth factor; co-administration of plasmids encoding for human vascular endothelial growth factor/plasmids encoding for fibroblast growth factor-2; or control plasmids were injected around 60 mu m ePTFE graft. Second, optimal small-diameter synthetic graft design for endothelialisation was explored in rabbit abdominal aorta model (n = 90). Various ePTFE grafts or pre-clotted polyester grafts were used with/without plasmids encoding for human vascular endothelial growth factor. Third, clinically used medium-size synthetic grafts were investigated with/without plasmids encoding for human vascular endothelial growth factor in dog carotid (n = 20) and femoral. arteries (n = 15). Endothelialisation was assessed in midgraft area with scanning electron microscopy. Results: In rats, plasmids encoding for human vascular endothelial growth factor enhanced endothelialisation; whereas co-administration of plasmids encoding for human vascular endothelial growth factor/plasmids encoding for fibroblast growth factor-2 had worst outcome at 1 week (NS), 2 weeks (P = 0.01) and 4 weeks (P = 0.02). In rabbits, pre-clotted polyester grafts had a trend for faster endothelialisation than ePTFE grafts (P = 0.08); whereas plasmids encoding for human vascular endothelial growth factor enhanced endothelialisation compared to controls at 2 weeks (P = 0.06), however, the effect reversed at 4 weeks (P = 0.03). In dogs, synthetic graft patency was improved by plasmids encoding for human vascular endothelial growth factor in femoral position (P = 0.103); whereas all carotid grafts were patent at 6 weeks. Conclusions: Thus, these data suggested that endothelialisation was fastest in pre-clotted polyester grafts; and that local application of plasmids encoding for human vascular endothelial growth factor had a potential to improve early endothelialisation and patency in synthetic vascular grafts.
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| 9. |
- Lövgren, Tanja, et al.
(författare)
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Complete and long-lasting clinical responses in immune checkpoint inhibitor-resistant, metastasized melanoma treated with adoptive T cell transfer combined with DC vaccination
- 2020
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Ingår i: Oncoimmunology. - : TAYLOR & FRANCIS INC. - 2162-4011 .- 2162-402X. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Development of T cell-directed immune checkpoint inhibitors (ICI) has revolutionized metastatic melanoma (MM) therapy, but <50% of treated patients experience durable responses. This phase I trial (NCT01946373) investigates the safety/feasibility of tumor-infiltrating lymphocyte (TIL) adoptive cell therapy (ACT) combined with dendritic cell (DC) vaccination in MM patients progressing on ICI. An initial cohort (5 patients) received TIL therapy alone to evaluate safety and allow for optimization of TIL expansion protocols. A second cohort (first-in-man, 5 patients) received TIL combined with autologous tumor lysate-loaded DC vaccination. All patients received cyclophosphamide/fludarabine preconditioning prior to, and intravenous (i.v.) IL-2 after, TIL transfer. The DC vaccine was given as five intradermal injections after TIL and IL-2 administration. [F-18]-FDG PET/CT radiology was performed to evaluate clinical response, according to RECIST 1.1 (on the CT part). Immunological monitoring was performed by flow cytometry and T-cell receptor (TCR) sequencing. In the safety/optimization cohort, all patients had a mixed response or stable disease, but none durable. In the combination cohort, two patients experienced complete responses (CR) that are still ongoing (>36 and >18 months, respectively). In addition, two patients had partial responses (PR), one still ongoing (>42 months) with only a small bone-lesion remaining, and one of short duration (<4 months). One patient died early during treatment and did not receive DC. Long-lasting persistency of the injected TILs was demonstrated in blood. In summary, we report clinical responses by TIL therapy combined with DC vaccination in 4 out of 4 treated MM patients who previously failed ICI.
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| 10. |
- Sandborg, Johanna, et al.
(författare)
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Effectiveness of a Smartphone App to Promote Healthy Weight Gain, Diet, and Physical Activity During Pregnancy (HealthyMoms) : Randomized Controlled Trial
- 2021
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Ingår i: JMIR mhealth and uhealth. - : JMIR Publications Inc. - 2291-5222. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Excessive gestational weight gain (GWG) during pregnancy is a major public health concern associated with negative health outcomes for both mother and child. Scalable interventions are needed, and digital interventions have the potential to reach many women and promote healthy GWG. Most previous studies of digital interventions have been small pilot studies or have not included women from all BMI categories. We therefore examined the effectiveness of a smartphone app in a large sample (n=305) covering all BMI categories. Objective: To investigate the effectiveness of a 6-month intervention (the HealthyMoms app) on GWG, body fatness, dietary habits, moderate-to-vigorous physical activity (MVPA), glycemia, and insulin resistance in comparison to standard maternity care. Methods: A 2-arm parallel randomized controlled trial was conducted. Women in early pregnancy at maternity clinics in Ostergotland, Sweden, were recruited. Eligible women who provided written informed consent completed baseline measures, before being randomized in a 1:1 ratio to either an intervention (n=152) or control group (n=153). The control group received standard maternity care while the intervention group received the HealthyMoms smartphone app for 6 months (which includes multiple features, eg, information; push notifications; self-monitoring; and feedback features for GWG, diet, and physical activity) in addition to standard care. Outcome measures were assessed at Linkoping University Hospital at baseline (mean 13.9 [SD 0.7] gestational weeks) and follow-up (mean 36.4 [SD 0.4] gestational weeks). The primary outcome was GWG and secondary outcomes were body fatness (Bod Pod), dietary habits (Swedish Healthy Eating Index) using the web-based 3-day dietary record Riksmaten FLEX, MVPA using the ActiGraph wGT3x-BT accelerometer, glycemia, and insulin resistance. Results: Overall, we found no statistically significant effect on GWG (P=.62); however, the data indicate that the effect of the intervention differed by pre-pregnancy BMI, as women with overweight and obesity before pregnancy gained less weight in the intervention group as compared with the control group in the imputed analyses (-1.33 kg; 95% CI -2.92 to 0.26; P=.10) and completers-only analyses (-1.67 kg; 95% CI -3.26 to -0.09; P=.031]). Bayesian analyses showed that there was a 99% probability of any intervention effect on GWG among women with overweight and obesity, and an 81% probability that this effect was over 1 kg. The intervention group had higher scores for the Swedish Healthy Eating Index at follow-up than the control group (0.27; 95% CI 0.05-0.50; P=.017). We observed no statistically significant differences in body fatness, MVPA, glycemia, and insulin resistance between the intervention and control group at follow up (P=.21). Conclusions: Although we found no overall effect on GWG, our results demonstrate the potential of a smartphone app (HealthyMoms) to promote healthy dietary behaviors as well as to decrease weight gain during pregnancy in women with overweight and obesity.
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