| 1. |
- Andersson, Sören, 1957-, et al.
(författare)
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Chimeric MOMP antigen
- 2014
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Patent (populärvet., debatt m.m.)abstract
- The present invention regards polypeptides capable of eliciting an immunological response that is protective against Chlamydia trachomatis. The polypeptide comprises a first amino acid sequence which has at least 90% homology with the amino acid sequence according to SEQ ID NO: 1 and a second amino acid sequence which has at least 90% homology with the amino acid sequence according to SEQ ID NO: 2. Furthermore, production of these polypeptides and pharmaceutical compositions comprising them are also provided.
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| 2. |
- Du, Juan, et al.
(författare)
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Prevalence of Oral Human Papillomavirus Infection among Youth, Sweden
- 2012
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Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention. - 1080-6040 .- 1080-6059. ; 18:9, s. 1468-1471
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Kalbina, Irina, 1961-, et al.
(författare)
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Expression of chimeric Chlamydia trachomatis MOMP protein antigen in Arabidopsis thaliana and Daucus carota
- 2011
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Ingår i: Molecular farming. - Bryssel : COST. ; , s. 38-38
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Konferensbidrag (refereegranskat)abstract
- 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.
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| 4. |
- Kumakech, Edward, 1977-, et al.
(författare)
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Integration of HIV and cervical cancer screening perceptions of healthcare providers and policy makers in Uganda
- 2014
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Ingår i: BMC Public Health. - : BioMed Central. - 1471-2458. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Lillsunde-Larsson, Gabriella, 1971-, et al.
(författare)
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Human Papillomavirus (HPV) and HPV 16-Variant Distribution in Vulvar Squamous Cell Carcinoma in Sweden
- 2012
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Ingår i: International Journal of Gynecological Cancer. - 1048-891X .- 1525-1438. ; 22:8, s. 1413-1419
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the human papillomavirus (HPV) and HPV type 16-variant distribution in a series of vulvar squamous cell carcinomas (VSCC) and to evaluate the impact of HPV and HPV 16-variant on prognosis.Methods: A series of 133 patients who had a diagnosis of VSCC (1983-2008) was selected for the study. Detection of 11 high-risk HPV types (16, 18, 31, 33, 39, 45, 51, 52, 56, 58, and 59) and 2 low-risk HPV types (6 and 11) was performed with real-time polymerase chain reaction. Samples positive for HPV 16 were further analyzed for variant determination of 7 positions in the E6 gene with polymerase chain reaction and pyrosequencing.Results: Forty (30.8%) of 130 tumors were found to be HPV positive. Human papillomavirus type 16 was found in 31 cases, HPV 18 was found in 2 cases, HPV 33 was found in 5 cases, and HPV 56 and HPV 59 were found in one case each. All but one tumor harboring HPV 16 were of European linage, and the 3 most common variants were E-p (n = 13), E-G350 (n = 7), and E-G131 (n = 5). HPV positivity was associated with the basaloid tumor type and occurred in significantly younger patients. Overall and recurrence-free survival rates were better in HPV-positive cases, but after correction for age and tumor size, HPV status was no longer an independent and significant prognostic factor. The survival rates of the various HPV 16 variants were not significantly different, but there was a trend of worse outcome for the E-G131-variant group.Conclusions: Human papillomavirus positivity of 30.8% is similar to other reports on VSCC. To our knowledge, this first variant determination of HPV 16 in vulvar carcinoma in a Swedish cohort indicated that the variant E-G131 may have an increased oncogenic potential in patients with VSCC.
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| 6. |
- Lillsunde-Larsson, Gabriella, 1971-, et al.
(författare)
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Prognostic impact of human papilloma virus (HPV) genotyping and HPV-16 subtyping in vaginal carcinoma
- 2013
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 129:2, s. 406-411
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThe objectives of this study are to investigate the human papilloma virus (HPV) distribution in vaginal cancer and to evaluate HPV-genotype as well as HPV16-variant impact on prognosis.MethodsSixty-nine patients diagnosed with primary vaginal carcinoma (1975-2002) were included in the study. Detection of twelve high-risk HPV (hr HPV) and two low-risk HPV (lr HPV) was performed with realtime-PCR. Samples positive for HPV-16 were analyzed for variants in the E6-gene with PCR and pyrosequencing.Results53.6% (37/69) of the tumors were found to be HPV-positive, mostly for HPV-16 (N=26). Other HPV-types were HPV-18 (N=2), HPV-31 (N=2), HPV-33 (N=2), HPV-45 (N=1), HPV-52 (N=2), HPV-56 (N=1) and HPV-58 (N=1). Only European subtypes of HPV-16 were represented and the two most common HPV-16-variants were E-p (N=13) and E-G350 (N=11). Patients with HPV-positive tumors (N=37) had a significantly (log-rank test=3341; p = 0.0008) superior 5-year overall survival rate as well as cancer-specific survival rate and progression-free survival rate (p = 0.0002; p = 0.0004), compared with patients with HPV-negative tumors (N=32). Interestingly, patients with HPV-16-positive tumors had a superior overall survival compared with patients with tumors containing other HPV-genotypes. In a Cox proportional multivariate analysis age, tumor size, and HPV-status were independent and significant prognostic factors with regard to overall survival rate.ConclusionsHPV-status is of prognostic importance in vaginal carcinoma and varies with viral genotype. In this era of HPV-vaccination, genotypes other than those included in the vaccination program could still lead to vaginal carcinoma with unfavorable prognosis.
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| 7. |
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| 8. |
- Lindh, Ingrid, 1982-, et al.
(författare)
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Oral delivery of plant-derived HIV-1 p24 antigen in low doses shows a superior priming effect in mice compared to high doses
- 2014
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Ingår i: Vaccine. - : Elsevier. - 0264-410X .- 1873-2518. ; 32:20, s. 2288-2293
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Tidskriftsartikel (refereegranskat)abstract
- 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
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| 9. |
- Lindh, Ingrid, 1982-, et al.
(författare)
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Oral delivery of transgenic plant-derived HIV-1 p24 antigen in low doses shows a superior priming effect in mice compared to higher doses
- 2012
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Ingår i: Retrovirology. - : BioMed Central (BMC). - 1742-4690. ; 9:Suppl. 2
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe 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.MethodsThree 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.ResultsThe 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).ConclusionSimple 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.
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| 10. |
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| 11. |
- Olsen, Birgitta, 1952-, et al.
(författare)
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Phenotypic and genetic characterisation of bacterial sexually transmitted infections in Bissau, Guinea-Bissau, West Africa : a prospective cohort study
- 2012
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Ingår i: BMJ Open. - London, United Kingdom : BMJ Publishing Group Ltd. - 2044-6055. ; 20:2
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 12. |
- Strid, Åke, 1960-, et al.
(författare)
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HIV, Chlamydia trachomatis and Helicobacter pylori vaccine antigen and proteinaceous adjuvant production in arabidopsis and carrot
- 2010
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Ingår i: Molecular farming. - Bryssel : COST. ; , s. 17-17
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Konferensbidrag (refereegranskat)abstract
- 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.
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| 13. |
- Tembe, Nelson, et al.
(författare)
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Reference Values for Clinical Laboratory Parameters in Young Adults in Maputo, Mozambique
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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