| 41. |
- Vinner, Lasse, et al.
(författare)
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Sequence analysis of HIV-1 isolates from Guinea-Bissau: selection of vaccine epitopes relevant in both West African and European countries.
- 2011
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463. ; 119:8, s. 487-497
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Tidskriftsartikel (refereegranskat)abstract
- For a CD8 epitope-based vaccine to match different geographic locations, the targeted epitopes for cytotoxic T-lymphocytes (CTLs) must be present in the local circulating HIV-1 strains. Secondly, the vaccine epitopes should match the host population HLA types. We characterized two new HIV-1 isolates from Guinea-Bissau. Also, we have identified 15 subdominant CD8 epitopes representing common HLA super-types theoretically covering most HLA alleles in any population. Herein we demonstrate that the selected vaccine epitopes are well conserved and simultaneously present in sequences from West Africa and Denmark. Use of the selected epitopes will likely ensure 10 immune targets in the majority of candidates for experimental therapeutic vaccination in both geographic regions. Our results warrant testing of the selected vaccine epitopes in both geographic locations.
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| 42. |
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| 43. |
- Wejse, Christian, et al.
(författare)
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Serum 25-hydroxyvitamin D in a West African population of tuberculosis patients and unmatched healthy controls
- 2007
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Ingår i: American Journal of Clinical Nutrition. - 1938-3207. ; 86:5, s. 1376-1383
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Tidskriftsartikel (refereegranskat)abstract
- Background: Little is known regarding vitamin D deficiency (VDD) in African populations and in tuberculosis (TB) patients. VDD has been shown to be associated with TB. Objective: We aimed to compare the degree of vitamin D insufficiency (VDI) and VDD in TB patients and healthy adult controls in a West African population. Design: An unmatched case-control study was performed at a Demographic Surveillance Site in Guinea-Bissau. Serum 25-hydroxyvitamin D-3 [25(OH)D-3] concentrations were measured in 362 TB patients and in 494 controls. Results: Hypovitammosis D [25(OH)D-3 <= 75 nmol/L] was more common in TB patients, but VDD [25(OH)D-3 <= 50 nmol/L] was more common and more severe in controls. We observed hypovitaminosis D in 467o (167/362) of the TB patients and in 39% (193/494) of the controls: the relative risk (RR) of hypovitaminosis D was 1.18 (95% Cl: 1.01. 1.38). VDD was observed in 8.5% (31/362) of the TB patients and in 13.2% (65/494) of the controls. The RR was 0.65 (95% Cl: 0.43,0.98), mainly because severe VDD [25(OH)D-3 <= 25 nmol/L] was observed in only I of 362 TB patients (0.2%) and in 24 of 494 controls (4.9%). After adjustment for background factors, hypovitaminosis D was not more frequent in TB patients than in healthy controls, but the mean serum 25(OH)D3 concentration remained lower. Conclusions: Hypovitammosis D was highly prevalent in TB patients and in healthy controls living at 12 degrees N; severe VDD was rare in TB patients. The finding indicates that the serum 25(OH)D3 concentration is associated with TB infection, but whether this role is a symptom or is causal was not established.
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| 44. |
- Wejse, Christian, et al.
(författare)
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Vitamin D as Supplementary Treatment for Tuberculosis A Double-blind, Randomized, Placebo-controlled Trial
- 2009
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 179:9, s. 843-850
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Tidskriftsartikel (refereegranskat)abstract
- Rationale Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis. Objectives: To test whether vitamin D supplementation of patients with tuberculosis (TB) improved clinical outcome and reduced mortality. Methods: We conducted a randomized, double-blind, place-bocontrolled trial in TB clinics at a demographic surveillance site in Guinea-Bissau. We included 365 adult patients with TB starting antituberculosis treatment; 281 completed the 12-month follow-up. The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment. Measurements and Main Results: The primary outcome was reduction in a clinical severity score (TBscore) for all patients with pulmonary TB. The secondary outcome was 12-month mortality. No serious adverse effects were reported; mild hypercalcemia was rare and present in both arms. Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo. Overall mortality was 15% (54 of 365) at I year of follow-up and similar in both arms (30 of 187 for vitamin D treated and 24 of 178 for placebo; relative risk, 1.19 [0.58-1.95]). HIV infection was seen in 36% (131 of 359): 21% (76 of 359) HIV-1, 10% (36 of 359) HIV-2, and 5% (19 of 357) HIV-1+2. Conclusions: Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB; it is possible that the dose used was insufficient. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN35212132).
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| 45. |
- Özkaya Sahin, Gülsen, et al.
(författare)
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Effect of Complement on HIV-2 Plasma Antiviral Activity Is Intratype Specific and Potent
- 2013
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Ingår i: Journal of Virology. - 1098-5514. ; 87:1, s. 273-281
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Tidskriftsartikel (refereegranskat)abstract
- Human immunodeficiency virus type-2 (HIV-2) infected individuals develop immunodeficiency with a considerable delay and transmit the virus at a lower rate as compared to HIV-1 infected. Conceivably, comparative studies on immune responsiveness of the HIV-1 and HIV-2 infected hosts may help to explain differences in pathogenesis and transmission between the two types of infection. Previous studies have shown that the neutralizing antibody response is more potent and broader in HIV-2 than HIV-1 infection. In the present study we have further examined the function of the humoral immune response and studied the potentiating effect of complement (C') on antiviral activity of plasma from singly HIV-1 or HIV-2 infected, as well as HIV-1/HIV-2 dually infected individuals. Neutralization and antibody-dependent complement-mediated inactivation of HIV-1 and HIV-2 isolates were tested in a plaque reduction assay using U87.CD4-CCR5 cells. Results showed that addition of C' increased intra-type antiviral activity of both HIV-1 and HIV-2 plasma, although the C' effect was more pronounced with HIV-2 than HIV-1 plasma. Using the area-under-curve (AUC)-based readout, multivariate statistical analysis confirmed that type of HIV infection was independently associated with the magnitude of the C' effect. Analysis carried out with purified IgG indicated that the C' effect was largely exerted through the classical C' pathway involving IgG in both HIV-1 and HIV-2 infections. In summary, these findings suggest that antibody binding to HIV-2 structures facilitates efficient use of C', and may thereby be one factor contributing to a strong antiviral activity present in HIV-2 infection.
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| 46. |
- Özkaya Sahin, Gülsen, et al.
(författare)
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Potent Intratype Neutralizing Activity Distinguishes Human Immunodeficiency Virus Type 2 (HIV-2) from HIV-1
- 2012
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Ingår i: Journal of Virology. - 1098-5514. ; 86:2, s. 961-971
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Tidskriftsartikel (refereegranskat)abstract
- HIV-2 has a lower pathogenicity and transmission rate than HIV-1. Neutralizing antibodies could be contributing to these observations. Here we explored side by side potency and breadth of intratype and intertype neutralizing activity (NAc) in plasma of 20 HIV-1, 20 HIV-2 and 11 dually HIV-1/2 (HIV-D) seropositive individuals from Guinea-Bissau, West Africa. Panels of primary isolates, five HIV-1 and five HIV-2, were tested in a plaque reduction assay using U87.CD4-CCR5 cells as targets. Intratype NAc in HIV-2 plasma was found to be considerably more potent, and also broader, than intratype NAc in HIV-1 plasma. This indicates that HIV-2 infected individuals display potent type-specific neutralizing antibodies, whereas such a strong type-specific antibodies are absent in HIV-1 infection. Furthermore, potency of intratype NAc was positively associated with viral load of HIV-1, but not HIV-2, suggesting that NAc in HIV-1 infection is more antigen stimulation-dependent than in HIV-2 infection where plasma viral loads typically are at least tenfold lower than in HIV-1 infection. Intertype NAc of both HIV-1 and HIV-2 infected was instead of low potency. HIV-D subjects had NAc to HIV-2 with similar high potency as singly HIV-2 infected individuals, whereas neutralization of HIV-1 remained poor, indicating that the difference in NAc between HIV-1 and HIV-2 infections depends on the virus itself. We suggest that immunogenicity and/or antigenicity, meaning the neutralization phenotype, of HIV-2 is distinct from HIV-1, and that HIV-2 may display structures that favour triggering of potent neutralizing antibody responses.
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