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  • 1.
    af Edholm, Karolina
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Lidman, Christer
    Karolinska University Hospital, Solna, Sweden.
    Andersson, Sören
    Örebro University, School of Medical Sciences.
    Solders, Göran
    Karolinska Institutet, Stockholm, Sweden.
    Paucar, Martin
    Karolinska University Hospital, Solna, Sweden.
    Clinical Reasoning: Leg weakness and stiffness at the emergency room2019In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 92, no 6, p. E622-E625Article in journal (Other academic)
    Abstract [en]

    A 48-year-old woman from the Maghreb came to the emergency department with insidious gait difficulties, urgency, and constipation starting 6 months prior to the visit. The patient's complaints consisted of weakness, stiffness, and pain in her legs. Her medical history consisted of Hashimoto thyroiditis and breast cancer, with the latter having motivated surgery 4 months prior to admission. Histopathologic examination had demonstrated ductal cancer sensitive to estrogen and mapping with sentinel node biopsy ruled out metastasis. For that reason, the patient was treated with local radiation given weekly over 1 month and treatment with tamoxifen was started. Physical examination upon admission demonstrated weakness and spasticity in both legs. Reflexes were brisk; bilateral nonsustained foot clonus and Babinski sign were also present. Bilateral dorsal flexion was reduced, but vibration and sensation to touch and pinprick were normal. Sphincter tonus was reduced; systemic manifestations such as myalgias, fever, skin rashes, uveitis, sicca, and arthritic joints were absent.

  • 2. da Silva, Zacarias J.
    et al.
    Oliveira, Inês
    Andersen, Andreas
    Dias, Francisco
    Rodrigues, Amabélia
    Holmgren, Birgitta
    Andersson, Sören
    Örebro University, School of Health and Medical Sciences.
    Aaby, Peter
    Changes in prevalence and incidence of HIV-1, HIV-2 and dual infections in urban areas of Bissau, Guinea-Bissau: is HIV-2 disappearing?2008In: AIDS (London), ISSN 0269-9370, E-ISSN 1473-5571, Vol. 22, no 10, p. 1195-1202Article in journal (Other academic)
    Abstract [en]

    Objectives: To assess the changes in HIV prevalence and incidence between 1996 and 2006 in urban areas of Bissau.

    Design: A cross-sectional survey of 384 randomly selected houses within a community-based follow-up study of HIV-1 and HIV-2.

    Methods: A total of 3242 individuals aged at least 15 years were eligible for inclusion. Participants were interviewed about behavioral and socio-economic factors and had a blood sample drawn. A total of 2548 individuals were tested for antibodies to HIV-1 and HIV-2, of whom 649 had taken part in a similar survey in 1996.

    Results: With 0.5% HIV dual reactions included, the overall HIV-1 prevalence was 4.6% (118 out of 2548) and the HIV-2 prevalence was 4.4% (112 out of 2548). The prevalence of HIV-1 increased more for women than men especially in the 25-34-year age group. HIV-2 prevalence decreased below 45 years of age but not for individuals more than 45 years old. The incidence rate between 1996 and 2006 was 0.5 per 100 person-years for HIV-1 and 0.24 per 100 person-years for HIV-2. Compared with a previous period from 1987 to 1996, the incidence of HIV-2 is declining whereas no significant increase in the incidence of HIV-1 was observed.

    Conclusions: The present study shows an increasing prevalence of HIV-1 and a decreasing prevalence of HIV-2 in Guinea-Bissau. HIV is generally a bigger problem for women. Despite the general decline in prevalence, HIV-2 may continue as an infection in older people, especially women.

  • 3.
    Du, Juan
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Nordfors, Cecilia
    Karolinska Institutet, Stockholm, Sweden.
    Ährlund-Richter, Andreas
    Karolinska Institutet, Stockholm, Sweden.
    Sobkowiak, Michal
    Karolinska Institutet, Stockholm, Sweden.
    Romanitan, Mircea
    Karolinska Institutet, Stockholm, Sweden.
    Näsman, Anders
    Karolinska Institutet, Stockholm, Sweden.
    Andersson, Sören
    Örebro University Hospital. Örebro University, School of Medical Sciences. Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
    Ramqvist, Torbjörn
    Karolinska Institutet, Stockholm, Sweden.
    Dalianis, Tina
    Karolinska Institutet, Stockholm, Sweden.
    Prevalence of Oral Human Papillomavirus Infection among Youth, Sweden2012In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 18, no 9, p. 1468-1471Article in journal (Refereed)
    Abstract [en]

    Human papillomavirus (HPV) causes cervical, head, and neck cancers. We studied 483 patients at a youth clinic in Stockholm, Sweden, and found oral HPV prevalence was 9.3% and significantly higher for female youth with than without cervical HPV infection (p = 0.043). Most oral HPV types matched the co-occurring cervical types.

  • 4. Eliasson, Henrik
    et al.
    Olcén, Per
    Sjöstedt, Anders
    Jurstrand, Margareta
    Bäck, Erik
    Örebro University, School of Health and Medical Sciences.
    Andersson, Sören
    Örebro University, School of Health and Medical Sciences.
    Kinetics of the immune response associated with tularemia: comparison of an enzyme-linked immunosorbent assay, a tube agglutination test, and a novel whole-blood lymphocyte stimulation test2008In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 15, no 8, p. 1238-1243Article in journal (Refereed)
    Abstract [en]

    We have developed and evaluated a novel and simplified whole-blood lymphocyte stimulation assay that focuses on the measurement of gamma interferon after 24 h of stimulation with whole-cell tularemia antigen and a tularemia enzyme-linked immunosorbent assay (ELISA) based on highly purified lipopolysaccharide antigen. Comparison of the kinetics of the two assays and those of the traditional tube agglutination test shows that the cellular immune response can be detected earlier by the lymphocyte stimulation assay. This test already shows a high proportion of positive results during the first week after the onset of the disease, may be applicable in everyday laboratory practice, and has the potential of changing routine diagnostics for tularemia. The new ELISA has a high sensitivity and becomes positive to a high degree during the second week of disease. 

  • 5.
    Esbjörnsson, Joakim
    et al.
    Department of Laboratory Medicine, Lund University, Malmö, Sweden; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
    Månsson, Fredrik
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Kvist, Anders
    Department of Clinical Sciences Lund, Lund University, Malmö, Sweden.
    da Silva, Zacarias J.
    National Public Health Laboratory, Bissau, Guinea-Bissau.
    Andersson, Sören
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    Fenyö, Eva Maria
    Department of Laboratory Medicine, Lund University, Malmö, Sweden.
    Isberg, Per-Erik
    Department of Statistics, Lund University School of Economics and Management, Lund, Sweden.
    Biague, Antonio J.
    National Public Health Laboratory, Bissau, Guinea-Bissau.
    Lindman, Jacob
    Department of Clinical Sciences Lund, Lund University, Malmö, Sweden.
    Palm, Angelica A.
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Rowland-Jones, Sarah L.
    Nuffield Department of Medicine, University of Oxford, Oxford, UK.
    Jansson, Marianne
    Department of Laboratory Medicine, Lund University, Malmö, Sweden.
    Medstrand, Patrik
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Norrgren, Hans
    Department of Clinical Sciences Lund, Lund University, Malmö, Sweden.
    Long-term follow-up of HIV-2-related AIDS and mortality in Guinea-Bissau: a prospective open cohort study2019In: The Lancet HIV, ISSN 2405-4704, E-ISSN 2352-3018, Vol. 6, no 1, p. E25-E31Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: HIV type 2 (HIV-2) is considered more benign and has fewer pathogenic consequences than HIV type 1 (HIV-1) for most infected individuals. However, reliable estimates of time to AIDS and mortality among those with HIV-2 infection are absent. We therefore aimed to compare the time to AIDS and mortality, and the CD4 T-cell dynamics between those infected with HIV-1 and HIV-2.

    METHODS: We did a prospective open cohort study. We included all police officers with regular employment from police stations in both urban and rural areas of Guinea-Bissau since Feb 6, 1990. We continued to include participants until Sept 28, 2009, and follow-up of HIV-1-positive and HIV-2-positive individuals continued until Sept 28, 2013. We collected blood samples at enrolment and at scheduled annual follow-up visits at police stations. We analysed longitudinal data from individuals infected with HIV-1 and HIV-2 according to time to AIDS, time to death, and T-cell dynamics. Time of HIV infection was estimated as the mid-timepoint between last HIV-seronegative and first HIV-seropositive sample. Data from an additional 2984 HIV-uninfected individuals from the same population were analysed to assess the effect of natural mortality on HIV-related mortality.

    FINDINGS: 872 participants tested HIV positive during the 23-year study period: 408 were infected with HIV-1 (183 infected before and 225 infected after enrolment) and 464 were infected with HIV-2 (377 before and 87 after enrolment). The median time from HIV infection to development of AIDS was 6·2 years (95% CI 5·4-7·1) for HIV-1 infection and 14·3 years (10·7-18·0) for HIV-2 infection (p<0·0001). The median survival time after HIV infection was 8·2 years (95% CI 7·5-8·9) for HIV-1 infection and 15·6 years (12·0-19·2) for HIV-2 infection (p<0·0001). Individuals who were infected with HIV-1 or HIV-2 before enrolment showed similar results. Comparison with uninfected individuals indicated limited confounding contribution from natural mortality. Mean CD4 percentages were higher in individuals with HIV-2 than in those with HIV-1 during early infection (28·0% [SE 1·3] vs 22·3% [1·7]; p=0·00094) and declined at a slower rate (0·4% [0·2] vs 0·9% [0·2] per year; p=0·028). HIV-2-infected individuals developed clinical AIDS at higher mean CD4 percentages (18·2%, IQR 7·2-25·4) than HIV-1-infected individuals (8·2%, 3·0-13·8; p<0·0001).

    INTERPRETATION: Our results show that both HIV-1-infected and HIV-2-infected individuals have a high probability of developing and dying from AIDS without antiretroviral treatment.

  • 6.
    Hadad, Ronza
    et al.
    Örebro Life Science Center, School of Science and Technology, Örebro University, Örebro, Sweden; Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Marks, Ellen
    Department of Medical Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
    Kalbina, Irina
    Örebro University, School of Science and Technology. Örebro Life Science Center, Örebro University, Örebro, Sweden.
    Schön, Karin
    Department of Medical Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Lycke, Nils
    Department of Medical Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology. Örebro Life Science Center, Örebro University, Örebro, Sweden.
    Andersson, Sören
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Protection against genital tract Chlamydia trachomatis infection following intranasal immunization with a novel recombinant MOMP VS2/4 antigen2016In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 124, p. 1078-1086Article in journal (Refereed)
    Abstract [en]

    The asymptomatic nature of most Chlamydia trachomatis infections and the lack of appropriate effects by current prevention and management call for vaccine development. We evaluated a recombinant subunit vaccine candidate based on the major outer membrane protein variable segments 2 and 4 (MOMP VS2/4). To achieve maximal immunogenicity and ease of production and purification, MOMP VS2/4 was constructed by using highly immunogenic sequences of MOMP only, thereby minimizing the presence of hydrophobic regions, and spacing the immunogenic epitopes with a flexible amino acid sequence. A purification tag was also added. The MOMP VS2/4 was given intranasally, with or without intravaginal boost, with cholera toxin (CT) adjuvant to C57BL/6 mice, which were screened for immunogenicity and protection against a live challenge infection with C. trachomatis serovar D. Bacterial shedding, cell-mediated responses, and antibody responses were monitored. Immunized mice exhibited significantly less bacterial shedding and were better protected against infertility as compared to unimmunized control mice. Immunizations stimulated both systemic and local specific antibody (IgG1, IgG2c, and IgA) responses, and primed T cells that produced interferon-c and interleukins 13 and 17 upon challenge with recall antigen. Thus, MOMP VS2/4, in combination with CT adjuvant, stimulated Th1, Th2, and Th17 effector cells, and generated protective immunity associated with less pathology. We regard MOMP VS2/4 as a promising candidate for further development into a mucosal chlamydial vaccine.

  • 7.
    Hadad, Ronza
    et al.
    Örebro University, School of Science and Technology.
    Schön, Karin
    University of Gothenburg, Gothenburg, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Andersson, Sören
    Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    Örebro University Hospital, Örebro, Sweden.
    Lycke, Nils
    University of Gothenburg, Gothenburg, Sweden.
    Optimization of infection in murine model with Chlamydia trachomatis for vaccine studies2013In: Chlamydia Basic Research Society: 2013 biannual meeting, 2013Conference paper (Refereed)
    Abstract [en]

    Background and Significance: Vaccine studies for Chlamydia trachomatis (Ct) have been hampered by the lack of an ideal murine model. Ct is not ideal for infection and subsequent pathology as it is a human pathogen and C. muridarum (Cm) may not be suitable due to vaccine specificity for Ct. There is currently no standardization of chlamydial infections in murine models concerning mouse strain, infecting agent and dose.

     

    Objectives: To investigate the Ct infection in mice, using different suppliers of mice, doses and the infective agents of Ct serovars D, E and Cm.

     

    Methods: C57BL/6 mice (Taconic; Harlan; in-house breeding mice) were inoculated intravaginally with 103-105 chlamydia  elementary bodies (EB). Vaginal samples were collected at 7-8 days intervals and analyzed using MicroTrak II Chlamydia EIA kit.

     

    Results: Taconic mice inoculated with Ct D with 105 EB showed the strongest infection with 30% of mice infected at day 21 (d21) as seen in figure 1. The number of infected mice and detected antigen (not shown) decreased rapidly after the first time-point (d8). In figure 2 infective agents were analyzed. Ct E did not infect any mice despite using a tenfold increased dose. Cm infection was detectable in 80% of the mice for up to d21.

     

    Conclusions: Ct D infected the mice for a period of 2-3 weeks. There was only a small difference between the suppliers in favor for Harlan mice. Ct D 105 EB was the infectious dose with the highest number of infected mice over time, however the appropriateness of that high bacterial load must be considered. Ct E did not infect these mice and Cm, a mouse pneumonitis strain, infected all mice and had the longest duration of infection. However, for vaccine studies, Cm may not be suitable due to lack of cross reactivity and Ct may still be used however vaginal sampling must be more frequent early on to show significant differences in bacterial shedding between immunized and non-immunized mice. 

  • 8.
    Hansson, Charlotta
    et al.
    Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
    Schön, Karin
    Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
    Kalbina, Irina
    Örebro University, School of Science and Technology.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Andersson, Sören
    Örebro University Hospital. Sch Sci & Technol, Orebro Life Sci Ctr, Univ Orebro, Orebro, Sweden; Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden .
    Bokarewa, Maria I.
    Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.
    Lycke, Nils Y.
    Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
    Feeding transgenic plants that express a tolerogenic fusion protein effectively protects against arthritis2016In: Plant Biotechnology Journal, ISSN 1467-7644, E-ISSN 1467-7652, Vol. 14, no 4, p. 1106-1115Article in journal (Refereed)
    Abstract [en]

    Although much explored, oral tolerance for treatment of autoimmune diseases still awaits the establishment of novel and effective vectors. We investigated if the tolerogenic CTA1(R7K)-COL-DD fusion protein can be expressed in edible plants and in this way induce oral tolerance and protect against arthritis. The fusion protein was recombinantly expressed in Arabidopsis thaliana plants, which were fed to H-2q restricted DBA/1 mice to assess the preventive effect on collagen-induced arthritis (CIA). The treatment resulted in fewer mice exhibiting disease and arthritis scores were significantly reduced. Immune suppression was evident in treated mice and serum biomarkers for inflammation as well as anti-collagen IgG responses were reduced. In spleen draining and lymph nodes, CD4+ T cell responses were reduced. Concomitant with a reduced effector T cell activity with lower IFNg, IL-13 and IL-17A production we observed an increase in IL-10 production to recall antigen stimulation in vitro, suggesting reduced Th1, Th2 and Th17 activity subsequent to upregulated IL-10 and regulatory T cell (Treg) functions. The present study shows that edible plants expressing a tolerogen were effective at stimulating CD4 T cell tolerance and in protecting against CIA disease. Our study conveys optimism as to the potential of using edible plants for oral treatment of rheumatoid arthritis.

  • 9.
    Kalbina, Irina
    et al.
    Örebro University, School of Science and Technology.
    Engstrand, Lars
    Dept Bacteriol, Swedish Inst Infect Dis Control SMI, Solna, Sweden.
    Andersson, Sören
    Örebro University Hospital, Örebro, Sweden; Dept Bacteriol, Swedish Inst Infect Dis Control SMI, Solna, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Expression of Helicobacter pylori TonB Protein in Transgenic Arabidopsis thaliana: toward production of vaccine antigens in plants2010In: Helicobacter, ISSN 1083-4389, E-ISSN 1523-5378, Vol. 15, no 5, p. 430-437Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was to produce a recombinant version of the highly antigenic Helicobacter pylori TonB (iron-dependent siderophore transporter protein HP1341) in transgenic plants as a candidate oral vaccine antigen. Materials and Methods: Using Agrobacterium-mediated gene transfer, we introduced three different constructs of the tonB gene into the genome of the model plant Arabidopsis thaliana. We investigated transgene insertion by PCR, produced TonB antibodies for analysis of the production of the recombinant protein in plants, verified the identity of the protein produced by mass spectrometry analysis, and analyzed the number of genetic inserts in the plants by Southern blotting. Results: Three different constructs of the expression cassette (full-length tonB, tonB truncated in the 5' end removing the codons for a transmembrane helix, and the latter construct with codons for the endoplasmic reticulum SEKDEL retention signal added to the 3' end) were used to find the most effective way to express the TonB antigen. Production of TonB protein was detected in plants transformed with each of the constructs, confirmed by both Western blotting and mass spectrometry analysis. No considerable differences in protein expression from the three different constructs were observed. The protein concentration in the plants was at least 0.05% of the total soluble proteins. Conclusions: The Helicobacter pylori TonB protein can be produced in Arabidopsis thaliana plants in a form that is recognizable by rabbit anti-TonB antiserum. These TonB-expressing plants are highly suitable for animal studies of oral adminstration as a route for immunization against Helicobacter infections.

  • 10.
    Kalbina, Irina
    et al.
    Örebro University, School of Science and Technology. Orebro Life Science Center.
    Lagerqvist, Nina
    Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Moiane, Bélisario
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Eduardo Mondlane University, Maputo, Mozambique.
    Ahlm, Clas
    Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Andersson, Sören
    Örebro University, School of Medical Sciences. Örebro Life Science Center, Department of Science and Technology, Örebro University, Örebro, Sweden; Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Falk, Kerstin I.
    Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Arabidopsis thaliana plants expressing Rift Valley fever virus antigens: Mice exhibit systemic immune responses as the result of oraladministration of the transgenic plants2016In: Protein Expression and Purification, ISSN 1046-5928, E-ISSN 1096-0279, Vol. 127, p. 61-67Article in journal (Refereed)
    Abstract [en]

    The zoonotic Rift Valley fever virus affects livestock and humans in Africa and on the Arabian Peninsula.The economic impact of this pathogen due to livestock losses, as well as its relevance to public health,underscores the importance of developing effective and easily distributed vaccines. Vaccines that can bedelivered orally are of particular interest.

    Here, we report the expression in transformed plants (Arabidopsis thaliana) of Rift Valley fever virusantigens. The antigens used in this study were the N protein and a deletion mutant of the Gn glycoprotein.Transformed lines were analysed for specific mRNA and protein content by RT-PCR and Westernblotting, respectively. Furthermore, the plant-expressed antigens were evaluated for their immunogenicityin mice fed the transgenic plants. After oral intake of fresh transgenic plant material, a proportionof the mice elicited specific IgG antibody responses, as compared to the control animals that were fedwild-type plants and of which none sero-converted.

    Thus, we show that transgenic plants can be readily used to express and produce Rift Valley Fever virusproteins, and that the plants are immunogenic when given orally to mice. These are promising findingsand provide a basis for further studies on edible plant vaccines against the Rift Valley fever virus.

  • 11.
    Kalbina, Irina
    et al.
    Örebro University, School of Science and Technology.
    Marks, Ellen
    University of Gothenburg, Gothenburg, Sweden.
    Lycke, Nils
    University of Gothenburg, Gothenburg, Sweden.
    Lindh, Ingrid
    Örebro University, School of Science and Technology.
    Unemo, Magnus
    Örebro University Hospital, Örebro, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Andersson, Sören
    Örebro University Hospital, Örebro, Sweden.
    Construction, immunogenicity and protective efficacy in mice of a prototype chimeric Chlamydia trachomatis MOMP vaccine candidate antigen2011Conference paper (Refereed)
    Abstract [en]

    A chimeric gene construct of Chlamydia trachomatis serovar E major outer membrane protein (MOMP) was designed, and expressed as a candidate vaccine antigen. The construct was based on known T and B cell epitopes located in the variable segment (VS) 2 and 4 loops of MOMP, and successfully expressed and purified in a recombinant Escherichia coli system. BALB/c mice were immunized intranasally with the chimeric MOMP antigen and Cholera toxin (CT) adjuvant, three immunizations with 10 days intervals. A final boost with the identical antigen preparation was given intravaginally. Challenge with live C. trachomatis serovar D was performed 10 days after boost. Antibodies in serum and vaginal washes were determined with the identical chimeric MOMP construct as antigen in ELISAs. All mice in vaccine groups (N=10/group and experiment) developed a strong antigen-specific IgG response in serum, and some also had detectable antigen-specific IgG in vaginal washes. An IgA response, albeit weaker, was detected in some of the mice both in serum and in vaginal washes.

    After challenge with C. trachomatis, 80 and 100% of the mice became infected in two experiments, respectively. However, the vaccinated groups cleared the infection significantly faster than control groups (all vaccinated mice healthy day 24 [90% day 16], compared to day 40 for controls).

    Thus, the new chimeric MOMP antigen construct gave rise to a significant immune response in mice (s-IgG). It also conferred substantial protection to infection caused by genital C. trachomatis infection of a different subtype.

  • 12.
    Kalbina, Irina
    et al.
    Örebro University, School of Science and Technology.
    Wallin, Anita
    Uppsala universitet, Uppsala, Sweden.
    Lindh, Ingrid
    Örebro University, School of Science and Technology.
    Engström, Peter
    Uppsala universitet, Uppsala, Sweden.
    Andersson, Sören
    Örebro University Hospital, Örebro, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    A novel chimeric MOMP antigen expressed in Escherichia coli, Arabidopsis thaliana, and Daucus carota as a potential Chlamydia trachomatis vaccine candidate2011In: Protein Expression and Purification, ISSN 1046-5928, E-ISSN 1096-0279, Vol. 80, no 2, p. 194-202Article in journal (Refereed)
    Abstract [en]

    The major outer membrane protein (MOMP) of Chlamydia trachomatis is a highly antigenic and hydrophobic transmembrane protein. Our attempts to express the full-length protein in a soluble form in Escherichia coli and in transgenic plants failed. A chimeric gene construct of C. trachomatis serovar E MOMP was designed in order to increase solubility of the MOMP protein but with retained antigenicity. The designed construct was successfully expressed in E. coli, in Arabidopsis thaliana, and in Daucus carota. The chimeric MOMP expressed in and purified from E. coli was used as antigen for production of antibodies in rabbits. The anti-chimeric MOMP antibodies recognized the corresponding protein in both E. coli and in transgenic plants, as well as in inactivated C. trachomatis elementary bodies. Transgenic Arabidopsis and carrots were characterized for the number of MOMP chimeric genetic inserts and for protein expression. Stable integration of the transgene and the corresponding protein expression were demonstrated in Arabidopsis plants over at least six generations. Transgenic carrots showed a high level of expression of the chimeric MOMP – up to 3% of TSP.

  • 13.
    Kalbina, Irina
    et al.
    Örebro University, School of Science and Technology.
    Wallin, Anita
    Uppsala universitet, Uppsala, Sweden.
    Lindh, Ingrid
    Örebro University, School of Science and Technology.
    Engström, Peter
    Uppsala universitet, Uppsala, Sweden.
    Andersson, Sören
    Universitetssjukhuset i Örebro, Örebro, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Expression of chimeric Chlamydia trachomatis MOMP protein antigen in Arabidopsis thaliana and Daucus carota2011In: Molecular farming: plants as a production platform for high value proteins / [ed] Ann Depicker, Bryssel: COST , 2011, p. 38-38Conference paper (Refereed)
    Abstract [en]

    Urogenital chlamydial infection, caused by Chlamydia trachomatis, is the main sexually transmitted infection in Sweden. Despite active programmes for detection and case finding, nearly 37 000 cases were reported in 2010. Serovar E strains are considered to cause approximately 40-50% of these cases. A vaccine would be highly valuable in order to control the epidemic.

    The major outer membrane protein (MOMP) of Chlamydia trachomatis is a highly antigenic and hydrophobic transmembrane protein. Our attempts to express the full-length protein in a soluble form in transgenic plants failed. A chimeric gene construct of Chlamydia trachomatis serovar E MOMP was designed in order to increase solubility of the MOMP protein but with retained antigenicity. The construct was based on known T and B cell epitopes located in the variable segment (VS) 2 and 4 loops of MOMP.

    The designed construct was successfully expressed in Arabidopsis thaliana, and in Daucus carota. A chimeric MOMP expressed in and purified from E. coli was used as antigen for production of antibodies in rabbits. The anti-chimeric MOMP antibodies recognized the corresponding protein in the transgenic plants, as well as in inactivated C. trachomatis elementary bodies. Transgenic Arabidopsis and carrots were characterized for the number of MOMP chimeric genetic inserts and for protein expression. Stable integration of the transgene and the corresponding protein expression were demonstrated in Arabidopsis plants over at least six generations. Transgenic carrots showed a high level of expression of the chimeric MOMP– up to 3% of TSP.

  • 14.
    Kumakech, Edward
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Pathology, Makerere University College of Health Sciences, Kampala, Uganda .
    Andersson, Sören
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Wabinga, Henry
    Department of Pathology, Makerere University College of Health Sciences, Kampala, Uganda .
    Berggren, Vanja
    Department of Health Sciences, Lund University, Lund, Sweden.
    Integration of HIV and cervical cancer screening perceptions and preferences of communities in Uganda2015In: BMC Women's Health, ISSN 1472-6874, E-ISSN 1472-6874, Vol. 15, no 1, article id 23Article in journal (Refereed)
    Abstract [en]

    Background: Despite the fact that HIV-positive women carry an increased risk of developing cervical cancer (CC) in comparison with HIV-negative women, HIV and CC screening programs in many developing countries have remained unintegrated. The objective of this study is to explore perceptions and preferences of community members in Uganda, including women, men, and village health teams, regarding the integration of HIV and CC screening services in a single-visit approach.

    Methods: This qualitative study was conducted in three districts in Uganda. Data were collected through focus group discussions with women and village health teams, and individual interviews with men. Respondents were purposely selected from among those linked to three CC clinics in the three districts. The content analysis method was used to analyze the data.

    Results: Three themes emerged from the data, namely appreciating the benefits of integration, worrying about the challenges of integration, and preferences for integration. The women endorsed the benefits. However, there were worries that integration would prolong the waiting time at the health facility and induce tiredness in both the healthcare providers and the women. There were also fears of being found positive for both HIV and CC and the consequences such as stress, self-isolation, and social conflicts. Participants, particularly the women, considered the challenges of screening integration to be manageable by, for example, taking a day off work to visit the hospital, delegating house chores to other family members, or taking a packed lunch on visiting the hospital.

    Conclusions: The community members in Uganda perceive the benefits of HIV and CC screening integration to outweigh the challenges, and expect that the challenges can be minimized or managed by the women. Therefore, when considering HIV and CC screening integration, it is important to not only recognize the benefits but also take into consideration the perceived challenges and preferences of community members.

  • 15.
    Kumakech, Edward
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Pathology, Makerere University, College of Health Sciences, Kampala, Uganda.
    Andersson, Sören
    Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Wabinga, Henry
    Department of Pathology, Makerere University, College of Health Sciences, Kampala, Uganda.
    Berggren, Vanja
    Division of Health Sciences, Lund University, Lund, Sweden.
    Integration of HIV and cervical cancer screening perceptions of healthcare providers and policy makers in Uganda2014In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 14, article id 810Article in journal (Refereed)
    Abstract [en]

    Background: HIV-positive women have an increased risk of developing cervical cancer (CC) compared to the HIV-negative women. Despite this, HIV and CC screening programs in many developing countries have remained disintegrated. Therefore, the objective of the study was to explore perceptions of healthcare providers (HCP) and policy makers (PM) about integration of HIV and CC screening services in Uganda.

    Methods: This was a qualitative study conducted among 16 participants comprising of 12 healthcare providers and 4 policy makers in Uganda. Data were collected through individual interviews. Participants were purposively selected from different level of health facilities with clinics for HIV and CC screening services. Content analysis method was used to analyze the data.

    Results: Three themes emerged from the data, namely appreciating benefits of integration, worrying about the limited health system capacity and potential consequences of integration and feeling optimistic about integration under improved health system conditions. The benefits embraced the women - particularly the HIV-positive women- but also men, healthcare providers and the health system or the government. There were worries that HIV stigma and shortage of healthcare workers would affect the effective delivery of the integrated program.

    Conclusion: Integration of HIV and CC screening can offer manifold benefits to all stakeholders in the health system, more so to the women. However, its feasibility in developing countries such as Uganda will most likely be hampered by weak and inefficient health systems. Therefore, when considering HIV and CC screening integration, it is important not to only recognize the benefits but also take into account resources requirements for addressing the existing weaknesses and inefficiencies in the health systems such as limited infrastructure, insufficient drugs and supplies, inadequate and poorly motivated healthcare workers.

  • 16.
    Kumakech, Edward
    et al.
    Örebro University, School of Health Sciences. School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.
    Andersson, Sören
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Wabinga, Henry
    Department of Pathology, Kampala Cancer Registry, Makerere University, Kampala, Uganda.
    Musubika, Caroline
    Department of Medical Microbiology, Immunology Laboratory, Makerere University, Kampala, Uganda.
    Kirimunda, Samuel
    Department of Medical Microbiology, Immunology laboratory, Makerere University, Kampala, Uganda.
    Berggren, Vanja
    Department of Health Sciences, Lund University, Lund, Sweden.
    Cervical cancer risk perceptions, sexual risk behaviors and sexually transmitted infections among Bivalent Human Papillomavirus vaccinated and non-vaccinated young women in Uganda-5 year follow up study2017In: BMC Women's Health, ISSN 1472-6874, E-ISSN 1472-6874, Vol. 17, article id 40Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies were conflicting regarding the associations between HPV vaccination, cervical cancer risk perceptions, high-risk sexual behaviors and STIs. This study compared the HPV-vaccinated and non-vaccinated young women in Uganda regarding cervical cancer risk perceptions, high-risk sexual behaviors, syphilis and HIV infections 5 years after vaccine implementation.

    Methods: This was a population-based comparative cross-sectional survey conducted in Uganda. The 438 participants were sexually active young women aged 15-24 years and mean age was 18.6 (SD 1.4). The majority (53.0%) were HPV-vaccinated in 2008 without assessment of sexual activity prior to HPV vaccination. Upon verbal assessment of sexual activity at the time of follow-up, data were collected using a questionnaire and laboratory testing of blood samples for syphilis and HIV infections.

    Results: There were no significant differences between the HPV-vaccinated and non-vaccinated groups regarding the prevalence of high-risk sexual behaviors, syphilis and HIV infections. Cervical cancer risk perceptions and age at sexual debut were nonetheless significantly lower among the vaccinated group compared to their non-vaccinated counterparts. However, HPV vaccination was not significantly associated to cervical cancer risk perceptions and early age at sexual debut in multivariate logistic regression analysis.

    Conclusions: We found no associations between HPV vaccination, cervical cancer risk perceptions, high-risk sexual behaviors, syphilis and HIV infections among young women in Uganda 5 years after vaccine implementation. Young girls in the study population were found to be sexually active at a young age, affirming the importance of targeting girls of younger age for HPV vaccination.

  • 17.
    Kumakech, Edward
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Makerere University College of Health Sciences, Kampala, Uganda.
    Berggren, Vanja
    Medical Faculty, Lund University, Lund; Global Health, Karolinska Institute, Stockholm.
    Lillsunde-Larsson, Gabriella
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro.
    Helenius, Gisela
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro.
    Kaliff, Malin
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University.
    Karlsson, Mats
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro.
    Musubika, Carol
    Makerere University College of Health Sciences, Kampala, Uganda.
    Kirimunda, Samuel
    Makerere University College of Health Sciences, Kampala, Uganda.
    Wabinga, Henry
    Makerere University College of Health Sciences, Kampala, Uganda.
    Andersson, Sören
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University.
    Prevalence, genotypes and risk factors for vaccine and non-vaccine types of Human Papillomavirus (HPV) infections among Bivalent HPV-16/18 vaccinated and non-vaccinated young women in Ibanda district Uganda: 5 year follow up studyManuscript (preprint) (Other academic)
  • 18.
    Kumakech, Edward
    et al.
    Örebro University, School of Health Sciences. Department of Pathology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda.
    Berggren, Vanja
    Faculty of Medicine, Lund University, Lund, Sweden; Department of Public Health (Global Health/IHCAR), Karolinska Institute, Stockholm, Sweden.
    Wabinga, Henry
    Department of Pathology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda.
    Lillsunde-Larsson, Gabriella
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden.
    Helenius, Gisela
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden.
    Kaliff, Malin
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University Hospital and Örebro University, Örebro, Sweden.
    Karlsson, Mats
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden.
    Kirimunda, Samuel
    Department of Pathology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda.
    Musubika, Caroline
    Department of Pathology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda.
    Andersson, Sören
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden.
    Significantly Reduced Genoprevalence of Vaccine-Type HPV-16/18 Infections among Vaccinated Compared to Non-Vaccinated Young Women 5.5 Years after a Bivalent HPV-16/18 Vaccine (Cervarix®) Pilot Project in Uganda2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 8, article id e0160099Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to determine the prevalence and some predictors for vaccine and non-vaccine types of HPV infections among bivalent HPV vaccinated and non-vaccinated young women in Uganda. This was a comparative cross sectional study 5.5 years after a bivalent HPV 16/18 vaccination (Cervarix®, GlaxoSmithKline, Belgium) pilot project in western Uganda. Cervical swabs were collected between July 2014-August 2014 and analyzed with a HPV genotyping test, CLART® HPV2 assay (Genomica, Madrid Spain) which is based on PCR followed by microarray for determination of genotype. Blood samples were also tested for HIV and syphilis infections as well as CD4 and CD8 lymphocyte levels. The age range of the participants was 15-24 years and mean age was 18.6(SD 1.4). Vaccine-type HPV-16/18 strains were significantly less prevalent among vaccinated women compared to non-vaccinated women (0.5% vs 5.6%, p 0.006, OR 95% CI 0.08(0.01-0.64). At type-specific level, significant difference was observed for HPV16 only. Other STIs (HIV/syphilis) were important risk factors for HPV infections including both vaccine types and non-vaccine types. In addition, for non-vaccine HPV types, living in an urban area, having a low BMI, low CD4 count and having had a high number of life time sexual partners were also significant risk factors. Our data concurs with the existing literature from other parts of the world regarding the effectiveness of bivalent HPV-16/18 vaccine in reducing the prevalence of HPV infections particularly vaccine HPV- 16/18 strains among vaccinated women. This study reinforces the recommendation to vaccinate young girls before sexual debut and integrate other STI particularly HIV and syphilis interventions into HPV vaccination packages.

  • 19.
    Lindh, Ingrid
    et al.
    Örebro University, School of Science and Technology.
    Andersson, Sören
    Universitetssjukhuset i Örebro, Örebro, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Plant-based production of HIV antigens: towards a candidate for an edible vaccine2010In: In Vivo, ISSN 0258-851X, E-ISSN 1791-7549, Vol. 24, no 3, p. 368-370Article in journal (Refereed)
  • 20.
    Lindh, Ingrid
    et al.
    Örebro University, School of Science and Technology.
    Bråve, Andreas
    The Public Health Agency of Sweden, Stockholm, Sweden.
    Hallengärd, David
    Karolinska Institute, Stockholm, Sweden.
    Andersson, Sören
    Örebro University Hospital, Örebro, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Oral delivery of plant-derived HIV-1 p24 antigen in low doses shows a superior priming effect in mice compared to high doses2012In: Molecular farming: plants as a production platform for high value proteins : FA action COST FA0804 / [ed] Herta Steinkellner, Bryssel: COST , 2012, p. 47-47Conference paper (Refereed)
  • 21.
    Lindh, Ingrid
    et al.
    Örebro University, School of Science and Technology. Örebro Life Sci Ctr, Univ Örebro, Örebro, Sweden; Sch Sci & Technol, Univ Örebro, Örebro, Sweden.
    Bråve, Andreas
    Swedish Institute for Communicable Disease Control (SMI), Stockholm, Sweden.
    Hallengärd, David
    Dept Microbiol Tumor & Cell Biol, Karolinska Inst, Stockholm, Sweden.
    Hadad, Ronza
    Örebro University, School of Science and Technology. Örebro Life Sci Ctr, Univ Örebro, Örebro, Sweden.
    Kalbina, Irina
    Örebro University, School of Science and Technology. Örebro Life Sci Ctr, Univ Örebro, Örebro, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology. Örebro Life Sci Ctr, Univ Örebro, Örebro, Sweden.
    Andersson, Sören
    Örebro University Hospital. Örebro Life Sci Ctr, Univ Örebro, Örebro, Sweden; Örebro University Hospital, Örebro, Sweden.
    Oral delivery of plant-derived HIV-1 p24 antigen in low doses shows a superior priming effect in mice compared to high doses2014In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 32, no 20, p. 2288-2293Article in journal (Refereed)
    Abstract [en]

    During early infection with human immunodeficiency virus type 1 (HIV-1), there is a rapid depletion of CD4+ T-cells in the gut-associated lymphoid tissue (GALT) in the gastrointestinal tract. Therefore, immediate protection at these surfaces is of high priority for the development of an HIV-1 vaccine. Thus, transgenic plants expressing HIV-1 antigens, which are exposed to immune competent cells in the GALT during oral administration, can be interesting as potential vaccine candidates. In the present study, we used two HIV-1 p24 antigen-expressing transgenic plant systems, Arabidopsis thaliana and Daucus carota, in oral immunization experiments. Both transgenic plant systems showed a priming effect in mice and induced humoral immune responses, which could be detected as anti-p24-specific IgG in sera after an intramuscular p24 protein boost. Dose-dependent antigen analyses using transgenic Arabidopsis thaliana indicated that low p24 antigen doses were superior to high p24 antigen doses

  • 22.
    Lindh, Ingrid
    et al.
    Örebro University, School of Science and Technology.
    Bråve, Andreas
    Swedish Institute for Communicable Disease Control, The Public Health Agency of Sweden, Stockholm, Sweden.
    Hallengärd, David
    Swedish Institute for Communicable Disease Control, The Public Health Agency of Sweden, Stockholm, Sweden.
    Hadad, Ronza
    Örebro University, School of Science and Technology.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Andersson, Sören
    Örebro University Hospital, Örebro, Sweden.
    Oral delivery of transgenic plant-derived HIV-1 p24 antigen in low doses shows a superior priming effect in mice compared to higher doses2012In: Retrovirology, ISSN 1742-4690, E-ISSN 1742-4690, Vol. 9, no Suppl. 2, article id P336Article in journal (Refereed)
    Abstract [en]

    Background

    The gut associated lymphoid tissue (GALT) includes around two thirds of the total lymphoid system. CD4+ T-cells in the GALT are a main target for HIV during primary infection. Thus, immunization targetting GALT is likely to be of importance for an effective vaccine strategy. Transgenic plants expressing HIV antigens can reach GALT conveniently. This system allows multiple boosts, has simple logistics (no cold chain, no injections) and large production capacity.

    Methods

    Three groups of mice were given extract from plant lines expressing HIV-1 p24 at (A) low level (20 ng/feeding); (B) high level (460 ng/feeding); (C) control (wild type, 0 ng). No adjuvant was included. The extracts were administered by gastric tube day 0, 14 and 28. On day 55 all mice were given an intramuscular (i.m.) boost with 10 micrograms of purified p24 antigen. Immune responses were determined by measurement of p24-antibodies in serum by ELISA.

    Results

    The mice immunized by the low dose plant line (A) showed a higher systemic immune response after i.m. boost compared to the high dose group (B). The w.t. controls (C) had undetectable p24-responses. The responses in group A were 3 to 10 times higher (ELISA OD values) than in group B. Pre-boost antibody responses were at background levels in all groups. Preliminary analyses indicate a predomninant Th1-type response (antigen-specific IgG2a higher than IgG1).

    Conclusion

    Simple and inexpensive means of vaccination are important in order to reach large numbers of people with effective vaccine regimens. The HIV-1 p24 low dose transgenic plant extracts given orally showed a superior priming effect in mice compared to the p24 high dose extracts. This could be an immunization method and route worth exploring further.

  • 23.
    Lindh, Ingrid
    et al.
    Örebro University, School of Science and Technology.
    Kalbina, Irina
    Örebro University, School of Science and Technology.
    Hedberg, Sara Thulin
    Scherbak, Nikolai
    Örebro University, School of Science and Technology.
    Sävenstrand, Helena
    Örebro University, School of Science and Technology.
    Bråve, Andreas
    Hinkula, Jorma
    Strid, Åke
    Örebro University, School of Science and Technology.
    Andersson, Sören
    Örebro University, School of Science and Technology.
    Feeding of mice with Arabidopsis thaliana expressing the HIV-1 subtype C p24 antigen gives rise to systemic immune responses2008In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 116, no 11, p. 985-994Article in journal (Refereed)
    Abstract [en]

    Development of transgenic edible plants, to be used as production, storage and delivery systems for recombinant vaccine antigens, is a promising strategy to obtain cost effective vaccines against infectious diseases, not the least for use in developing countries. Therefore, we used Agrobacterium tumefaciens-mediated gene transfer to introduce the p24 gag gene encoding the nucleocapsid protein from HIV-1 subtype C into the Arabidopsis thaliana plant genome. Eighteen plant lines were confirmed positive for the p24 gene by PCR, four of these lines showed an apparent homozygous phenotype when grown on selective medium and these lines also showed transcription of the p24 gene into its corresponding mRNA. The mRNA in all four cases generated the p24 protein in plants, as verified by western blot analysis. The plants were shown to contain between 0.2 µg and 0.5 µg p24 protein per g of fresh tissue. Analysis of the localisation of the p24 protein showed that stem tissue contained the largest amount of protein, more than twice as much as leaf tissue, whereas no p24 protein was detected in roots. By using Southern blotting, we found that 4, 2-3, 2 and 1 T-DNA insertion events took place in the four lines 1, 2, 7, and 10, respectively. The genetic insertions of line 1 were stable from the T1 to the T4 generation and gave rise to the p24 protein in all cases, as verified by western blotting. In mice fed with fresh transgenic A. thaliana (line 10), anti-gag IgG was obtained in serum after a booster injection with recombinant p37Gag. No immune response was observed after equal booster injection of untreated mice or mice fed with A. thaliana WT plants.

  • 24.
    Lindh, Ingrid
    et al.
    Örebro University, School of Science and Technology.
    Wallin, Anita
    Evolutionsbiologiskt Centrum, Uppsala universitet.
    Kalbina, Irina
    Örebro University, School of Science and Technology.
    Sävenstrand, Helena
    Örebro University, School of Science and Technology.
    Engström, Peter
    Uppsala Universitet.
    Andersson, Sören
    Smittskyddsinstitutet.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Production of the p24 capsid protein from HIV-1 subtype C in Arabidopsis thaliana and Daucus carota using an endoplasmic reticulum-directing SEKDEL sequence in protein expression constructs2009In: Protein Expression and Purification, ISSN 1046-5928, E-ISSN 1096-0279, Vol. 66, no 1, p. 46-51Article in journal (Refereed)
    Abstract [en]

    An optimized gene expression construct was designed in order to increase the accumulation of the HIV-1 subtype C p24 protein in Arabidopsis thaliana and carrot (Daucus carota) plants. An ER retention signal was introduced into the genetic construct generating a p24 protein containing a SEKDEL amino acid sequence at its C-terminus. Mature A. thaliana plants and carrot cells were transformed using Agrobacterium tumefaciens carrying the improved pGreen0229/p24_SEKDEL vector. Several transgenic plant lines were obtained from both plant species by growth on selective medium and confirmed by PCR. Transformed lines were analyzed for p24 protein content by western blotting using anti-p24-specific antibodies and by Southern blotting to establish the number of copies of the insert in the plant nuclear genome. To estimate the accumulation levels of p24 protein in the plants, ELISA was run using soluble plant extracts. By comparing these results with our previous findings, the ER retention signal increased the level of p24 protein 5-fold in the Arabidopsis thaliana plants. In carrot taproot, the content of p24_SEKDEL protein was approximately half of that in Arabidopsis on a fresh weight basis and was stable in planta for several months. However, on a total soluble protein basis, carrots produced considerable higher levels of the p24_SEKDEL protein than Arabidopsis.

  • 25.
    Malm, Kerstin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Andersson, Sören
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Norrgren, Hans
    Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
    Biague, Antonio
    National Public Health Laboratory (LNSP), Bissau, Guinea-Bissau.
    Månsson, Fredrik
    Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
    Ballard, R.
    Center for Global Health, Centers for Disease Control and Protection, Atlanta GA, USA.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Analytical evaluation of nine serological assays for diagnosis of syphilis2015In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 29, no 12, p. 2369-2376Article in journal (Refereed)
    Abstract [en]

    Background: The diagnosis of syphilis is most frequently dependent on antibody detection with serological assays. Assays for both treponemal and non-treponemal antibodies are needed to provide a sensitive and specific diagnosis. For decades, a first screening has been done with non-treponemal assays, followed by treponemal. However, in recent years, following laboratory automation, the reverse sequence screening algorithms have been developed, using a treponemal assay as the initial screening test.

    Objective: To evaluate serological assays for treponemal and non-treponemal antibodies, to use in reverse algorithm screening of syphilis.

    Material and methods: Six treponemal assays (one IgM-specific assay), two non-treponemal assays and one novel dual point-of-care (POC) assay for serological diagnosis of syphilis were evaluated. Serum samples from Guinea-Bissau and Sweden were examined, as well as two performance panels and samples from blood donors. Sensitivity and specificity were calculated for each assay, using different assays as gold standard test.

    Results: The Macro-Vue RPR Card test was the most sensitive non-treponemal test and the TrepSure Anti-Treponema EIA Screen and the SeroDia TP-PA were the most sensitive and specific treponemal assays. Among the automated assays, both the Liaison Treponema Screen and Architect Syphilis TP showed high sensitivity, however, the former had clearly higher specificity.

    Conclusions: In resourced settings, where the reverse sequence algorithm is preferred for screening, an automated treponemal immunoassay for initial screening subsequently followed by the TrepSure test or TP-PA assay as a second treponemal assay appear highly effective. Finally, a quantitative highly sensitive non-treponemal assay, e.g. the Macro-Vue RPR Card test, could then be used as a supplementary test to evaluate activity of the syphilis infection.

  • 26.
    Malm, Kerstin
    et al.
    Örebro University, School of Health Sciences. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Andersson, Sören
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Sundqvist, Martin
    Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Evaluation of the Veris MDx (TM) system for quantification of Hepatitis B DNA and Hepatitis C and HIV-1 RNA in a medium sized University Hospital2016In: Journal of Clinical Virology, ISSN 1386-6532, E-ISSN 1873-5967, Vol. 82, p. S27-S27Article in journal (Refereed)
    Abstract [en]

    Introduction: In the diagnosis and treatment of Hepatitis B (HBV), Hepatitis C (HCV) and HIV, it is crucial to detect and quantify viral nucleic acid. Patients on therapy are monitored continuously to out-rule relapses or reinfections (HCV) while for patients with HIV these tests are important to early on detect potential break-throughs due to resistance development. Quantification methods are today more standardized and fast but still with no opportunity to analyze the samples with full random access. Recently the VERIS MDxTMplatform from Beckman Coulter with this possibility was launched.

    Objectives: To evaluate a new, random access laboratory instrument for the simultaneous detection and quantification of HBV, HCV and HIV-1.

    Methods: WHO standards for HBV-DNA, HCV-RNA and HIV-1-RNA provided from the National Institute for Biological Standards and Control (NIBSC) were diluted down to the designated lowest level of detection and analyzed in triplicates on the Veris MDxTM(Beckman Coulter Inc. 250 S. Kraemer Blvd. Brea, CA U.S.A.) instrument. Plasma samples from routine laboratory testing were analyzed and compared to the routine methods used at our hospital or the referral hospital, for HBV; COBAS®AmpliPrep/COBAS® TaqMan®HBV Test, v2.0 (Roche Molecular Diagnostics, 4300 Hacienda Drive, Pleasanton, CA, USA) (Karolinska University Hospital Huddinge), for HCV; COBAS® TaqMan®HCV Test v2.0 for use with the High Pure System (Roche) (Örebro) and for HIV; Aptima HIV-1 Quant Dx Assay (Hologic Inc. 250 Campus Drive Marlborough, MA, USA) (Örebro). 55 samples for HBV, 120 samples for HCV and 60 samples for HIV have been analyzed so far. The absolute majority of samples for HCV and HIV analysis were from patients on treatment. All viral load data were analyzed as log10-transformed values.

    Results: The Veris MDxTMshowed good compatibility to the designated quantities of the WHO standards (except for HIV-1 where a slight over-quantification could be observed for dilutions in the higher range, i.e. >1000 copies/mL). The limits of detection assigned by the manufacturer could be confirmed. In clinical samples the Veris MDxTM showed similar results to the comparators with a correlation for quantifiable samples of 0.94 (HBV), 0.98 (HCV) and 0.98 (HIV). The Veris MDxTMshowed a slightly higher sensitivity though as DNA/RNA was detected in 4 samples for HBV, 8 for HCV and 7 for HIV when the comparator method did not. The opposite was seen in 0, 0 and 6 samples respectively.

    Conclusion: The Veris MDxTMfor quantitative analysis of HBV, HCV and HIV nucleic acids showed good correlation to the comparator methods used in this study with a tendency of higher sensitivity for the detection of HBV and HCV. The Instrument provides an easy, fast and flexible method for quantification of RNA and DNA in plasma samples.

  • 27. Norrgren, Hans R.
    et al.
    Bamba, Sana
    Larsen, Olav
    Da Silva, Zacarias
    Aaby, Peter
    Koivula, Tuija
    Andersson, Sören
    Örebro University, School of Health and Medical Sciences.
    Increased prevalence of HTLV-1 in patients with pulmonary tuberculosis coinfected with HIV, but not in HIV-negative patients with tuberculosis2008In: Journal of Acquired Immune Deficiency Syndromes, ISSN 1525-4135, E-ISSN 1944-7884, Vol. 48, no 5, p. 607-610Article in journal (Refereed)
    Abstract [en]

    Background: Few and inconclusive results have been presented regarding the influence of human T-lymphotropic virus 1 (HTLV-1) infection on the risk of acquiring tuberculosis (TB). Methods: In 1994-1997, we performed a prospective study on hospitalized adult patients with pulmonary TB in Guinea-Bissau and compared the clinical outcome in HIV-2 and HIV-negative patients. We determined the prevalence of HTLV-1 in all patients screened and diagnosed with TB in that study and compared the infection rate with a serosurvey of HTLV-1 in a population sample from a community-based study conducted at the same time and in the same city. Results: In the TB group, a total of 32 (11.4%) of 280 patients were positive for HTLV-1. This was significantly higher compared with the population-based group in which 74 (3.5%) of 2117 were HTLV-1 positive [crude odds ratio (OR) = 3.6; 95% confidence interval (CI) 2.2 to 5.6, P < 0.001]. However, in a logistic regression analysis controlling for age, gender, and HIV result, the difference was no longer significant (OR = 1.61; 95% CI 0.95 to 2.70, P = 0.074). In HIV-negative patients, no association was found between HTLV-1 and TB (OR = 1.18; 95% CI 0.48 to 2.89, P = 0.71), whereas a significant association was found in HIV-positive patients (OR = 2.41; 95% CI 1.26 to 4.61, P = 0.008). Conclusions: The immunosuppressive effect of HTLV-1 alone was not enough to increase the risk of TB in a highly endemic country, but HTLV-1 increased the risk of TB among HIV-infected individuals.

  • 28.
    Olsen, Birgitta
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Månsson, Fredrik
    Infectious Diseases Research Unit, Department of Clinical Sciences, Lund, University, Malmö, Sweden.
    Camara, Cidia
    National Public Health Laboratory (LNSP), Bissau, Guinea-Bissau.
    Monteiro, Mario
    National Public Health Laboratory (LNSP), Bissau, Guinea-Bissau.
    Biai, Ansu
    National Public Health Laboratory (LNSP), Bissau, Guinea-Bissau.
    Alves, Alfredo
    Department of Obstetrics and Gynaecology, Simaõ Mendes National Hospital, Bissau, Guinea-Bissau.
    Andersson, Sören
    WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden .
    Norrgren, Hans
    Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
    Unemo, Magnus
    WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Phenotypic and genetic characterisation of bacterial sexually transmitted infections in Bissau, Guinea-Bissau, West Africa: a prospective cohort study2012In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 20, no 2, article id e000636Article in journal (Refereed)
    Abstract [en]

    Background: Knowledge regarding characteristics and transmission of Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium and antibiotic resistance in N gonorrhoeae in Guinea-Bissau, West Africa, is entirely lacking.

    Objectives: To characterise N gonorrhoeae, C trachomatis and M genitalium samples from Guinea-Bissau and to define bacterial populations, possible transmission chains and for N gonorrhoeae spread of antibiotic-resistant isolates.

    Design: Prospective cohort study.

    Setting: Two sexual health and family planning clinics, Bissau, Guinea-Bissau.

    Participants: Positive samples from 711 women and 27 men.

    Material and methods: Positive samples for N gonorrhoeae (n=31), C trachomatis (n=60) and M genitalium (n=30) were examined. The gonococcal isolates were characterised with antibiograms, serovar determination and N gonorrhoeae multiantigen sequence typing (NG-MAST). The C trachomatis ompA gene and the M genitalium mgpB gene were sequenced, and phylogenetic analyses were performed.

    Results: For N gonorrhoeae, the levels of resistance (intermediate susceptibility) to ciprofloxacin, erythromycin, rifampicin, ampicillin, tetracycline, penicillin G and cefuroxime were 10% (0%), 6% (10%), 13% (10%), 68% (0%), 74% (0%), 68% (16%) and 0% (84%), respectively. All isolates were susceptible to cefixime, ceftriaxone, spectinomycin and azithromycin, and the minimum inhibitory concentrations of kanamycin (range: 8-32 mg/l) and gentamicin (range: 0.75-6 mg/l) were low (no resistance breakpoints exist for these antimicrobials). 19 NG-MAST sequence types (STs) (84% novel STs) were identified. Phylogenetic analysis of the C trachomatis ompA gene revealed genovar G as most prevalent (37%), followed by genovar D (19%). 23 mgpB STs were found among the M genitalium isolates, and 67% of isolates had unique STs.

    Conclusions: The diversity among the sexually transmitted infection (STI) pathogens may be associated with suboptimal diagnostics, contact tracing, case reporting and epidemiological surveillance. In Guinea-Bissau, additional STI studies are vital to estimate the STI burden and form the basis for a national sexual health strategy for prevention, diagnosis and surveillance of STIs.

  • 29.
    Strid, Åke
    et al.
    Örebro University, School of Science and Technology.
    Lagerqvist, Nina
    The Public Health Agency of Sweden, Stockholm, Sweden.
    Moiane, B.
    Eduardo Mondlane University, Maputo, Mozambique.
    Kalbina, Irina
    Örebro University, School of Science and Technology.
    Andersson, Sören
    Örebro University Hospital, Örebro, Sweden.
    Falk, Kerstin I.
    The Public Health Agency of Sweden, Stockholm, Sweden.
    Expression of Rift Valley Fever virus antigens in Arabidopsis thaliana for oral consumption2012In: Molecular farming: plants as a production platform for high value proteins, Bryssel: COST , 2012Conference paper (Refereed)
    Abstract [en]

    Rift Valley Fever (RVF) is a viral disease affecting both domesticated ruminants and humans. Since 1931, when the causative agent was first discovered in Kenya [1], there have been several severe outbreaks mostly in Sub-Saharan Africa [2]. RVF is now considered as one of Africa’s most important viral zoonoses and is endemic in large parts of the continent. In recent years, RVF has also emerged into Saudi Arabia and the Yemen, where it now is endemic [3]. Common symptoms of an ongoing RVF infection in humans are influenza-like, although more severe clinical manifestations such as hemorrhagic fever, ocular disease and encephalitis are often observed [4]. Outbreaks in livestock may have large economic impact.

     

    The etiological agent, the RVF virus (RVFV), is an enveloped negative sense RNA virus, which belongs to the genus Phlebovirus in the Bunyaviridae family. As the other members of this family, RVFV has three gene segments; the L, M, and S segments. The L segment encodes an RNA-dependent RNA polymerase and the M-segment the glycoproteins and a non-structural protein. By using an ambisense strategy, the S-segment codes for the highly immunogenic nucleocapsid protein (N) and a non-structural protein [4].

     

    The main focus of this project is to establish the plant production of an RVF vaccine candidate, primarily for oral administration. This is an attractive model for vaccination, especially of livestock. The two currently available vaccines for animals are a live attenuated variant, albeit teratogenic, or a weaker inactivated vaccine which requires annual boosters. There is no human vaccine available for general use.

     

    Similarly to our previous expression studies with the HIV p24 protein [5-7], the Helicobacter pylori TonB protein [8], and the Chlamydia trachomatis MOMP chimera [9], we have used Agrobacterium tumefaciens-mediated gene transfer to introduce genes encoding RVFV antigens into Arabidopsis thaliana. Transformed model plants have been created that express the full length RVFV N protein or deletion mutants of the two RVF glycoproteins. Analyses of transformants are on-going (PCR for genomic insertion, cDNA synthesis and RT-PCR for mRNA occurrence, and Western blotting for protein production) and in at least some cases have been shown to carry the corresponding recombinant protein. Mice are being fed fresh transgenic A. thaliana and the subsequent immune response towards the N protein and the glycoproteins will be closely monitored and evaluated by neutralisation test, Western blot and ELISA. Thereafter, the mice will be challenged with the wild-type virus and the protective efficacy of the edible vaccine will be determined.

     

    References

    1. Daubney R, Garnham P (1931) J Patol Bacterio 34: 8922-8926; 2. Gerdes G (2004) Rev Sci Tech 23: 613-623; 3. Balkhy H, Memish Z (2003) Int J Antimicrob Agents 21: 153-157; 4. Flick R, Bouloy M (2005) Curr Mol Med 5: 827-834; 5. Lindh, I., Kalbina, I., Thulin, S., Scherbak, N., Sävenstrand, H., Bråve, A., Hinkula, J., Strid, Å. & Andersson, S. (2008) APMIS 116, 985-994; 6. Lindh, I., Wallin, A., Kalbina, I., Sävenstrand, H., Engström, P., Andersson, S. & Strid, Å. (2009) Prot. Expr. Purif. 66, 46-51; 7. Lindh, I., Andersson, S. & Strid, Å. (2010) In vivo 24, 368-370; 8. Kalbina, I., Engstrand, L., Andersson, S. & Strid, Å. (2010) Helicobacter 15, 430-437; 9. Kalbina I., Wallin A., Lindh I., Engström P., Andersson S. & Strid Å. (2011) Prot. Expr. Purif. 80, 194-202.

  • 30.
    Strid, Åke
    et al.
    Örebro University, School of Science and Technology.
    Lindh, Ingrid
    Örebro University, School of Science and Technology.
    Kalbina, Irina
    Örebro University, School of Science and Technology.
    Andersson, Sören
    Örebro University Hospital, Örebro, Sweden.
    Plant-based production of vaccine antigens and adjuvants2010Conference paper (Refereed)
    Abstract [en]

    Vaccination is the most successful form of prevention of infectious diseases but only a few dozen of several hundred infectious diseases can be prevented in this way due to the extreme cost of vaccine development and due to costly production. Obviously, there is a growing need for large scale and low cost production of valuable proteins, such as vaccine antigens, and alternative methods to mammalian and microbial production systems are also desirable. Plants/plant cells may offer such an option. In our project, we use plants for synthesis of vaccine antigens and adjuvant proteins. Among targeted diseases are HIV, Chlamydia trachomatis (CT) and Helicobacter pylori infections. Novel genetic constructs have been designed for production of optimized antigen proteins and several transformation techniques and intracellular protein production sites are being examined for yield optimization. Both Arabidopsis and carrot have been succesfully used as production hosts and plant-produced antigens against HIV and CT have been used in immunization trials in laboratory mice, giving rise to systemic immune responses. For CT, our designed chimeric protein has also been shown to protect against the disease. Moreover, to further increase the effect of vaccine antigens, we also use plants to produce protein-based adjuvants for inclusion in vaccine formulations. This project is part of the transnational COST network FA0804: ‘Molecular farming - plants as production platform for high-value proteins’. A few slides will be devoted to the brief presentation of the collaboration within this network, which is comprised of research groups in 23 EU countries and a few associated groups outside EU.

  • 31.
    Strid, Åke
    et al.
    Örebro University, School of Science and Technology.
    Lindh, Ingrid
    Örebro University, School of Science and Technology.
    Kalbina, Irina
    Örebro University, School of Science and Technology.
    Engstrand, Lars
    Smittskyddsinstitutet, The Public Health Agency, Solna, Sweden.
    Lycke, Nils
    Gothenburg University, Gothenburg, Sweden.
    Marks, Ellen
    Gothenburg University, Gothenburg, Sweden.
    Applequist, Steve
    Karolinska Institute, Stockholm, Sweden.
    Andersson, Sören
    Örebro University Hospital, Örebro, Sweden.
    HIV, Chlamydia trachomatis and Helicobacter pylori vaccine antigen and proteinaceous adjuvant production in arabidopsis and carrot2010In: Molecular farming: plant as a production platform for high value proteins / [ed] Nunzia Scotti, Bryssel: COST , 2010, p. 17-17Conference paper (Refereed)
    Abstract [en]

    In our project, we use plants for synthesis of vaccine antigens and adjuvant proteins. Among targeted diseases are HIV, Chlamydia trachomatis (CT) and Helicobacter pylori (HP) infections. Novel genetic constructs have been designed for production of optimized antigen proteins and several transformation techniques and intracellular protein production sites are being examined for yield optimization. Both Arabidopsis thaliana (HIV, CT, HP) and carrot (HIV, CT) have been successfully used as production hosts and plant-produced antigens against HIV (primarily the p24 protein), CT (own designed chimera of the MOMP protein) and HP (different versions of the TonB protein). For HIV and CT these antigens have been used in immunization trials in laboratory mice, giving rise to systemic immune responses. For this purpose both consumption of plant tissue and distribution of purified antigens have been used. For CT, the administration of the recombinant protein has also been shown to protect against the disease in mice. Moreover, to further increase the effect of vaccine antigens, we also use plants to produce protein-based adjuvants for inclusion in vaccine formulations. These adjuvants are based either on the bacterial flagellin protein or are cholera toxin-derived chimeric proteins.

  • 32.
    Tembe, Nelson
    et al.
    Instituto Nacional de Saúde, Maputo, Mozambique; Dept Lab Med, Karolinska Inst, Huddinge, Sweden; Fac Med, Eduardo Mondlane Univ, Maputo, Mozambique.
    Joaquim, Orvalho
    Instituto Nacional de Saúde, Maputo, Mozambique.
    Alfai, Eunice
    Instituto Nacional de Saúde, Maputo, Mozambique.
    Sitoe, Nadia
    Instituto Nacional de Saúde, Maputo, Mozambique.
    Viegas, Edna
    Instituto Nacional de Saúde, Maputo, Mozambique; Dept Lab Med, Huddinge, Karolinska Inst, Sweden; Fac Med, Eduardo Mondlane Univ, Maputo, Mozambique.
    Macovela, Eulalia
    Fac Med, Eduardo Mondlane Univ, Maputo, Mozambique; Hosp Cent Maputo, Maputo, Mozambique.
    Goncalves, Emilia
    Fac Med, Eduardo Mondlane Univ, Maputo, Mozambique; Hosp Cent Maputo, Maputo, Mozambique.
    Osman, Nafissa
    Fac Med, Eduardo Mondlane Univ, Maputo, Mozambique.;Hosp Cent Maputo, Maputo, Mozambique..
    Andersson, Sören
    Örebro University Hospital.
    Jani, Ilesh
    Instituto Nacional de Saúde, Maputo, Mozambique.
    Nilsson, Charlotta
    Dept Lab Med, Karolinska Inst, Huddinge, Sweden; Publ Hlth Agcy Sweden, Solna, Sweden; Dept Microbiol Tumor & Cell Biol, Karolinska Inst, Stockholm, Sweden.
    Reference Values for Clinical Laboratory Parameters in Young Adults in Maputo, Mozambique2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 5, article id e97391Article in journal (Refereed)
    Abstract [en]

    Background: Clinical laboratory reference values from North American and European populations are currently used in most Africans countries due to the absence of locally derived reference ranges, despite previous studies reporting significant differences between populations. Our aim was to define reference ranges for both genders in 18 to 24 year-old Mozambicans in preparation for clinical vaccine trials.

    Methods: A cross-sectional study including 257 volunteers (102 males and 155 females) between 18 and 24 years was performedat a youth clinic in Maputo, Mozambique. All volunteers were clinically healthy and human immunodeficiency virus, Hepatitis B virus and syphilis negative. Median and 95% reference ranges were calculated for immunological, hematological and chemistry parameters. Ranges were compared with those reported based on populations in other African countries and the US. The impact of applying US NIH Division of AIDS (DAIDS) toxicity tables was assessed.

    Results: The immunology ranges were comparable to those reported for the US and western Kenya. There were significant gender differences in CD4(+) T cell values 713 cells/mu L in males versus 824 cells/mu L in females (p < 0.0001). Hematologic values differed from the US values but were similar to reports of populations in western Kenya and Uganda. The lower and upper limits of the ranges for hemoglobin, hematocrit, red blood cells, white blood cells and lymphocytes were somewhat lower than those from these African countries. The chemistry values were comparable to US values, with few exceptions. The upper limits for ALT, AST, bilirubin, cholesterol and triglycerides were higher than those from the US. DAIDStables for adverse events predicted 297 adverse events and 159 (62%) of the volunteers would have been excluded.

    Conclusion: This study is the first to determine normal laboratory parameters in Mozambique. Our results underscore the necessity of establishing region-specific clinical reference ranges for proper patient management and safe conduct of clinical trials.

  • 33.
    Thulin Hedberg, Sara
    et al.
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Eriksson, Lorraine
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    Demontis, Maria A.
    Imperial College, St Mary’s Hospital, London, UK.
    Mölling, Paula
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Sundqvist, Martin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Taylor, Graham
    Imperial College, St Mary’s Hospital, London, UK.
    Malm, Kerstin
    Örebro University, School of Health Sciences. Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Andersson, Sören
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    Droplet digital PCR for absolute quantification of proviral load of human T-cell lymphotropic virus (HTLV) types 1 and 22018In: Journal of Virological Methods, ISSN 0166-0934, E-ISSN 1879-0984, Vol. 260, p. 70-74Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Human T-lymphotrophic virus (HTLV) types 1 and 2 cause lifelong infection whereby most infected individuals are asymptomatic whilst a minority develop infection-related disease. These latter patients invariably have been found to have high proviral load (PVL). Therefore, infected patients are monitored by determining the proportion of lymphocytes that are infected with HTLV-1/2. An increase in PVL has been shown to represent an increasing risk of developing HTLV-associated diseases. Monitoring of PVL requires a reliable and sensitive method. In this study assays based on droplet digital PCR (ddPCR) were established and evaluated for detection and quantification of HTLV-1/2.

    OBJECTIVES: To develop two parallel assays to detect the tax genes and determine the PVL of HTLV-1 and -2.

    STUDY DESIGN: Sixty-seven clinical samples from patients infected with HTLV-1 or HTLV-2 were analysed. The samples had previously been analysed with a qPCR and a comparison between ddPCR and qPCR was performed. The specificity of the assays were determined by analyzing samples from 20 healthy blood donors.

    RESULTS: The ddPCR was a stable and sensitive method for detection and quantification of HTLV-1 and -2. When comparing the qPCR and ddPCR the correlation was high (Pearsons correlation coefficient 0.96). The variability of the ddPCR was very low with intra-assay coefficient of variation (CV) of 0.97-3.3% (HTLV-1) and 1.7-8.2% (HTLV-2) and inter-assay CV of 1.8-6.1% (HTLV-1) and 1.2-12.9% (HTLV-2).

    CONCLUSIONS: The ddPCR reliably quantified HTLV DNA in clinical samples and could be a useful tool for monitoring of PVLs in HTLV-infected individuals.

  • 34.
    Viegas, Edna Omar
    et al.
    Instituto Nacional de Saúde, Maputo, Mozambique; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden; Eduardo Mondlane University, Maputo, Mozambique; .
    Augusto, Orvalho
    Eduardo Mondlane University, Maputo, Mozambique.
    Ismael, Nália
    Instituto Nacional de Saúde, Maputo, Mozambique.
    Kaliff, Malin
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Lillsunde-Larsson, Gabriella
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Ramqvist, Torbjörn
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, Charlotta
    Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden; Department of Microbiology, Public Health Agency of Sweden, Stockholm, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Falk, Kerstin
    Department of Microbiology, Public Health Agency of Sweden, Stockholm, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Osman, Nafissa
    Eduardo Mondlane University, Maputo, Mozambique; Hospital Central de Maputo, Maputo, Mozambique.
    Jani, Ilesh Vindorai
    Instituto Nacional de Saúde, Maputo, Mozambique.
    Andersson, Sören
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    Human papillomavirus prevalence and genotype distribution among young women and men in Maputo city, Mozambique2017In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, no 7, article id e015653Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Human papillomavirus (HPV) is a well-known cause of cervical cancer, the second most frequent cancer in female African populations. This study aimed at determining the prevalence of HPV infections and the genotype distribution in young adults aged 18-24, in Maputo city, Mozambique, and to assess the suitability of commercially available HPV vaccines.

    METHODS: This cross-sectional study was conducted between 2009 and 2011 at a youth clinic in Maputo Central Hospital. Cervical and urethral samples were obtained from 236 women and 176 men, respectively. Demographic and behavioural data were collected using structured questionnaires. HPV genotyping was performed for 35 different high, probably or possibly high-risk and low-risk HPV types using the CLART Human Papillomavirus 2.

    RESULTS: HPV prevalence was 168/412 (40.8%; 95% CI 36.0 to 45.5) and was significantly higher in women than in men (63.6%vs10.2%). HPV52 was the most frequent type found in women, followed by HPV35, -16,-53, -58,-6 and -51. In men, HPV51 ranked the highest, followed by HPV6, -11,-52, -59 and -70. HIV infection and sexual debut before 18 years of age were associated with multiple HPV infections (OR 3.03; 95% CI 1.49 to 6.25 and OR 6.03; 95% CI 1.73 to 21.02, respectively). Women had a significantly higher HPV infection prevalence than men (p<0.001). The 9-valent HPV vaccine would cover 36.8% of the high-risk genotypes circulating in women in this study, compared with 26.3% and 15.8% coverage by the bivalent and quadrivalent vaccines, respectively.

    CONCLUSION: This study confirmed the high burden of HPV infections in young women in Maputo city, Mozambique. The HPV prevalence was associated with high-risk sexual behaviour. Sex education and sexually transmitted infection prevention interventions should be intensified in Mozambique. Only a proportion of the high-risk HPV genotypes (37%) were covered by currently available vaccines.

  • 35.
    Viegas, Edna Omar
    et al.
    Instituto Nacional de Saúde, Maputo, Mozambique; Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden; Faculdade de Medicina, Universidade Eduardo Mondlane, Maputo, Mozambique .
    Tembe, Nelson
    Instituto Nacional de Saúde, Maputo, Mozambique; Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden; Faculdade de Medicina, Universidade Eduardo Mondlane, Maputo, Mozambique .
    Macovela, Eulalia
    Faculdade de Medicina, Universidade Eduardo Mondlane, Maputo, Mozambique; Hospital Central de Maputo, Maputo, Mozambique .
    Goncalves, Emilia
    Faculdade de Medicina, Universidade Eduardo Mondlane, Maputo, Mozambique; Hospital Central de Maputo, Maputo, Mozambique .
    Augusto, Orvalho
    Faculdade de Medicina, Universidade Eduardo Mondlane, Maputo, Mozambique .
    Ismael, Nalia
    Instituto Nacional de Saúde, Maputo, Mozambique .
    Sitoe, Nadia
    Instituto Nacional de Saúde, Maputo, Mozambique .
    De Schacht, Caroline
    Elizabeth Glaser Pediatric AIDS Foundation, Maputo, Mozambique.
    Bhatt, Nilesh
    Instituto Nacional de Saúde, Maputo, Mozambique .
    Meggi, Bindiya
    Instituto Nacional de Saúde, Maputo, Mozambique .
    Araujo, Carolina
    Faculdade de Medicina, Universidade Eduardo Mondlane, Maputo, Mozambique.
    Sandström, Eric
    Department of Education and Clinical Research, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden .
    Biberfeld, Gunnel
    Public Health Agency of Sweden, Solna, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden .
    Nilsson, Charlotta
    Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden; Public Health Agency of Sweden, Solna, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden .
    Andersson, Sören
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden .
    Jani, Ilesh
    Instituto Nacional de Saúde, Maputo, Mozambique .
    Osman, Nafissa
    Faculdade de Medicina, Universidade Eduardo Mondlane, Maputo, Mozambique; Hospital Central de Maputo, Maputo, Mozambique.
    Incidence of HIV and the Prevalence of HIV, Hepatitis B and Syphilis among Youths in Maputo, Mozambique: A Cohort Study2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 3, article id e0121452Article in journal (Refereed)
    Abstract [en]

    Background: Prevalence of HIV in Mozambique among individuals aged 15-49 years is 11.5%. The HIV prevalence is higher in women than in men across the country, peaking at ages 25-29 years and 35-39 years, respectively. In this study, we aimed at determining the prevalence and incidence of HIV, prevalence of Hepatitis B (HBV), and prevalence of syphilis in youths. We also characterized a cohort of youths for future participation in phase I/II HIV vaccine trials.

    Methods: The study was conducted at a youth clinic in Maputo Central Hospital from August 2009 to October 2011. Youths of both genders aged 18-24 years (n = 1380) were screened for HIV using a sequential algorithm of two immunochromatographic assays, HBV using an enzyme linked immunosorbant test, and syphilis using a treponemal immunochromatographic strip test. The HIV seronegative participants (n = 1309) were followed-up for 12 months with quarterly study visits. The clinical and behavioral data were collected using structured questionnaires. The HIV seroconversions were confirmed by a molecular assay.

    Results: The study population was female dominant (76.8%). All participants had a formal education, with 44.6% studying for technical or higher education degrees. The mean age at sexual debut was 16.6 years (SD: +/-1.74), with 85.6% reporting more than one sexual partner in life. The screening showed the prevalence of HIV, HBV, and syphilis at 5.1% (95% CI: 3.97-6.31), 12.2% (95% CI 10.5%-14.0%), and 0.36% (95% CI 0.15%-0.84%), respectively. The HIV incidence rate was found to be 1.14/100 person years (95% CI: 0.67-1.92). Retention rates were stable throughout the study being 85.1% at the last visit.

    Conclusion: Incidence of HIV in this cohort of youths in Maputo was relatively low. Also, the prevalence of HIV and syphilis was lower than the national values in this age group. However, the HBV prevalence was higher than in previous reports in the country.

  • 36.
    Viegas, Edna Omar
    et al.
    Instituto Nacional de Saúde, Maputo, Mozambique; Division of Clinical Microbiology, Department of Laboratory Medicine, Huddinge, Karolinska Institutet, Sweden; Universidade Eduardo Mondlane, Maputo, Mozambique.
    Tembe, Nelson
    Instituto Nacional de Saúde, Maputo, Mozambique; Division of Clinical Microbiology, Department of Laboratory Medicine, Huddinge, Karolinska Institutet, Sweden; Universidade Eduardo Mondlane, Maputo, Mozambique.
    Nilsson, Charlotta
    Division of Clinical Microbiology, Department of Laboratory Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; Public Health Agency of Sweden (Folkhälsomyndigheten), Stockholm, Sweden.
    Meggi, Bindiya
    Instituto Nacional de Saúde, Maputo, Mozambique.
    Maueia, Cremildo
    Instituto Nacional de Saúde, Maputo, Mozambique.
    Augusto, Orvalho
    Universidade Eduardo Mondlane, Maputo, Mozambique.
    Stout, Richard
    Bioject Medical Technologies Inc, Tualatin OR, United States.
    Scarlatti, Gabriella
    Institute for Research and Health Care (IRCCS), San Raffaele Scientific Institute, Milan, Italy.
    Ferrari, Guido
    Department of Surgery and Molecular Genetics and Microbiology, Duke University Medical Center, Durham NC, United States.
    Earl, Patricia
    Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAD)/National Institutes of Health (NIH), Bethesda MD, United States.
    Wahren, Britta
    Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Sören
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Robb, Merlin
    The Henry M. Jackson Foundation for the Advancement of Military Medicine, The Military HIV Research Program, Walter Reed Army Institute of Research, Bethesda MD, United States.
    Osman, Nafissa
    Universidade Eduardo Mondlane, Maputo, Mozambique.
    Biberfeld, Gunnel
    Microbiology,Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Jani, Ilesh
    Instituto Nacional de Saúde, Maputo, Mozambique.
    Sandström, Eric
    Microbiology,Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Intradermal HIV-1 DNA immunization using needle-free ZetajetTM injection followed by HIV-modified vaccinia virus Ankara vaccination is safe and immunogenic in Mozambican young adults: a phase I randomized controlled trial2018In: AIDS Research and Human Retroviruses, ISSN 0889-2229, E-ISSN 1931-8405, Vol. 34, no 2, p. 193-205Article in journal (Refereed)
    Abstract [en]

    We assessed safety and immunogenicity of HIV-DNA priming using Zetajet<sup>TM</sup>, a needle-free device intradermally followed by intramuscular HIV-MVA boosts, in 24 healthy Mozambicans. Volunteers were randomized to receive three immunizations of 600 µg (n = 10; 2 x 0.1mL) or 1200 µg (n = 10; 2 x 0.2mL) of HIV-DNA (3 mg/mL), followed by two boosts of 10<sup>8</sup>pfu HIV-MVA. Four subjects received placebo saline injections. Vaccines and injections were safe and well tolerated with no difference between the two priming groups. After three HIV-DNA immunizations, IFN-γ ELISpot responses to Gag were detected in 9/17 (53%) vaccinees, while none responded to Env. After the first HIV-MVA, the overall response rate to Gag and/or Env increased to 14/15 (93%); 14/15 (93%) to Gag and 13/15 (87%) to Env. There were no significant differences between the immunization groups in frequency of response to Gag and Env or magnitude of Gag responses. Env responses were significantly higher in the higher-dose group (median 420 vs 157.5 SFC/million PBMC, p=0.014). HIV-specific antibodies to subtype C gp140 and subtype B gp160 were elicited in all vaccinees after the second HIV-MVA, without differences in titers between the groups. Neutralizing antibody responses were not detected. Two (13%) of 16 vaccinees, one in each of the priming groups, exhibited antibodies mediating antibody-dependent cellular cytotoxicity to CRF01_AE. In conclusion, HIV-DNA vaccine delivered intradermally in volumes of 0.1-0.2 mL using Zetajet<sup>TM</sup> was safe and well tolerated. Priming with the 1200 µg dose of HIV-DNA generated higher magnitudes of ELISpot responses to Env.

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