Karolinska Institute and Karolinska Hospital

Stockholm, Sweden

Karolinska Institute and Karolinska Hospital

Stockholm, Sweden
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Boggiano C.,U.S. National Institutes of Health | Eichelberg K.,U.S. National Institutes of Health | Ramachandra L.,U.S. National Institutes of Health | Shea J.,Aeras | And 6 more authors.
Vaccine | Year: 2017

Tuberculosis (TB) is the major cause of death from infectious diseases around the world, particularly in HIV infected individuals. TB vaccine design and development have been focused on improving Bacille Calmette-Guérin (BCG) and evaluating recombinant and viral vector expressed Mycobacterium tuberculosis (Mtb) proteins, for boosting BCG-primed immunity, but these approaches have not yet yielded significant improvements over the modest effects of BCG in protecting against infection or disease. On March 7-8, 2016, the National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on "The Impact of Mtb Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" with the goal of defining immune mechanisms that could be targeted through novel research approaches, to inform vaccine design and immune therapeutic interventions for prevention of TB. The workshop addressed early infection events, the impact of Mtb evolution on the development and maintenance of an adaptive immune response, and the factors that influence protection against and progression to active disease. Scientific gaps and areas of study to revitalize and accelerate TB vaccine design were discussed and prioritized. These included a comprehensive evaluation of innate and Mtb-specific adaptive immune responses in the lung at different stages of disease; determining the role of B cells and antibodies (Abs) during Mtb infection; development of better assays to measure Mtb burden following exposure, infection, during latency and after treatment, and approaches to improving current animal models to study Mtb immunogenicity, TB disease and transmission. © 2017.

Savic I.,Karolinska Institute and Karolinska Hospital
Frontiers in Neuroscience | Year: 2014

Whilst many studies show sex differences in cerebral asymmetry, their mechanisms are still unknown. This report describes the potential impact of sex hormones and sex chromosomes by comparing MR data from 39 male and 47 female controls and 33 men with an extra X-chromosome (47, XXY). Methods: Regional asymmetry in gray and white matter volumes (GMV and WMV) was calculated using voxel based moprhometry (SPM5), by contrasting the unflipped and flipped individual GMV and WMV images. In addition, structural volumes were calculated for the thalamus, caudate, putamen, amygdala, and hippocampus, using the FreeSurfer software. Effects of plasma testosterone and estrogen on the GMV and WMV, as well on the right/left ratios of the subcortical volumes were tested by multi-regression analysis. Results: All three groups showed a leftward asymmetry in the motor cortex and the planum temporale, and a rightward asymmetry of the middle occipital cortex. Both asymmetries were more pronounced in 46, XY males than 46, XX females and 47, XXY males, and were positively correlated with testosterone levels. There was also a rightward asymmetry of the vermis and leftward GMV asymmetry in the cerebellar hemispheres in all groups. Notably, cerebellar asymmetries were larger in 46, XX females and 47, XXY males, but were not related to sex hormone levels. No asymmetry differences between 46, XX females and 47, XXY males, and no overall effects of brain size were detected. Conclusion: The asymmetry in the planum temporale area and the occipital cortex seem related to processes associated with testosterone, whereas the observed cerebellar asymmetries suggest a link with X-chromosome escapee genes. Sex differences in cerebral asymmetry are moderated by sex hormones and X-chromosome genes, in a regionally differentiated manner. © 2014 Savic.

Faust H.,Skåne University Hospital | Dillner J.,Skåne University Hospital | Dillner J.,Karolinska Institute and Karolinska Hospital
Journal of General Virology | Year: 2013

induce type-specific neutralizing antibodies against a small number of hypervariable residues positioned in surface-exposed loops of the major capsid protein L1. To investigate the importance of these residues for neutralization, cross-neutralization, L2 incorporation and genome encapsidation, ten surface-exposed amino acid residues in four hypervariable loops of L1 were mutated. VLPs containing mutated or WT L1, with or without WT L2, were produced in 293TT cells using pseudovirion expression vectors. The mutations reduced the ability to induce neutralizing antibodies and to incorporate the L2 protein in the capsid. Ability to induce crossneutralizing antibodies and to encapsidate pseudogenomes were completely abrogated. In summary, the surface-exposed L1 loops are important for the function of the HPV particle. © 2013 SGM.

Faust H.,Skåne University Hospital | Jelen M.M.,University of Ljubljana | Poljak M.,University of Ljubljana | Klavs I.,National Institute of Public Health | And 4 more authors.
Journal of Clinical Virology | Year: 2013

Background: Serology for human papillomaviruses (HPV) types -16 and -18 is established as an important tool for studies of HPV vaccinology and epidemiology. However, as there are a large number of oncogenic genital types of HPV there is a need for development of high-throughput, validated HPV serological assays that can be used for more comprehensive seroepidemiological studies and for research on multivalent HPV vaccines. Objectives: To develop a multiplexed pseudovirion-based serological assay (PsV-Luminex) encompassing 21 HPV types and validate the method by correlating the serology with the presence of type specific HPV DNA in cervical samples. Study design: Cervical swabs from 3,291 unvaccinated women attending organized cervical screening in Slovenia were tested with 3 different HPV DNA detection methods and presence of HPV DNA compared to presence of serum antibodies to pseudovirions from 15 genital HPV types (HPV-6,-11,-16,-18,-31,-33,-35,-39,-45,-52,-56,-58,-59,-68,-73). Results: On average 51% of the HPV DNA positive women were seropositive for the same HPV type that was detected in the cervical specimen. We found a strong correlation with presence of HPV DNA and antibodies to the same HPV type for 13/15 genital HPV types (median OR. =5.7, CI 95%. =2.4-12.9). HPV-52 serology failed the validation and HPV-11 serology could not be validated because only a single woman was positive for HPV-11 DNA. The correlation between serology and HPV DNA status tended to be stronger among women infected with single HPV type (median OR. =10.5, CI 95%. =2.4-48.4) than among women with multiple HPV infections (median OR. =4.6, CI 95%. =1.8-11.7). Conclusions: A multiplexed HPV PsV-Luminex assay has been developed and validated to correlate with natural HPV infection for 13 HPV types, thus enabling more comprehensive studies in HPV epidemiology and vaccine research. © 2013 Elsevier B.V.

Ucakar V.,National Institute of Public Health | Jelen M.M.,University of Ljubljana | Faust H.,Skåne University Hospital | Poljak M.,University of Ljubljana | And 4 more authors.
Vaccine | Year: 2013

Objectives: To estimate seroprevalence of 11 high-risk (hr) HPV types and four low-risk (lr) HPV types among 20-64 years old Slovenian women participating in the population-based cervical cancer screening program. Methods: Serum samples from 3259 women were tested for HPV type-specific antibodies with a multiplexed pseudovirion-based serological assay (PsV-Luminex). Results: Seropositivity for any of the 15 HPV types was 65.7%, any of the 11 hr-HPV types 59.2%, and any of the four lr-HPV types 33.1%. Antibodies against at least one of the four vaccine HPV types (HPV 6, 11, 16, 18) were detected in 40.8% women. Among hr-HPV types, seropositivity was highest for HPV 16 (25.2%) and among lr-HPV types for HPV 6 (19.1%). Age-specific HPV16 seropositivity was highest among 30-39 years old (29.6%) and decreased with increasing age to 14.0% among 60-64 years old. Conclusion: The lifetime sexual exposure to genital HPV types is substantial, emphasising the need for HPV vaccination. © 2013 The Authors.

Aro K.,University of Helsinki | Back L.,University of Helsinki | Loimu V.,University of Helsinki | Saarilahti K.,University of Helsinki | And 6 more authors.
European Archives of Oto-Rhino-Laryngology | Year: 2016

Management of head and neck cancer influences both physical and mental wellbeing. Measuring the health-related quality of life (HRQoL) is important, as various treatment modalities are associated with significant morbidity and mortality. In this prospective cohort study, we tested the feasibility of the generic 15D HRQoL instrument in 214 head and neck cancer patients managed with surgery, definitive (chemo)radiotherapy, or with combined modality treatment. HRQoL was assessed at baseline and three times after treatment onset during 1 year, and compared with that of general population standardized for age and sex. At baseline, the patients’ mean 15D score was significantly worse compared with general population. Overall HRQoL was at lowest at 3 months after treatment onset, it gradually improved towards 12 months but never reached baseline levels. The dimensions “vitality”, “distress”, “depression” and “sexual activity” showed marked deterioration at 3 months after the treatment onset, but improved gradually during 12 months. The 15D instrument seems useful for evaluation of HRQoL of head and neck cancer patients. Dimensions reflecting mental wellbeing improved gradually after 3 months, but they seldom reached baseline levels. The support for patients at the time of diagnosis, during treatment, and recovery is emphasized. © 2015, Springer-Verlag Berlin Heidelberg.

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