During the serial passage of Mycobacterium bovis bacillus Calmette-Guérin (BCG) in different countries after initial seed distribution from the Pasteur Institute, specific insertions and deletions in the genome among BCG substrains were observed and speculated to result in differences in immunological activities. 'Early-shared strains' of BCG (Russia, Moreau, Japan, Sweden, Birkhaug), distributed by the Pasteur Institute, which conserve three types of mycolate (alpha, methoxy, keto) in cell wall, exhibited stronger activities of induction of nitric oxide, interleukin-1beta (IL-1beta), IL-6, IL-8, IL-12 and tumor necrosis factor (TNF)-alpha, from human epithelial cell line A549, human myelomonocytic cell line THP-1 and mouse bone marrow cells in the presence of interferon-gamma (IFN-gamma) than did 'late-shared strains' of BCG (Danish, Glaxo, Mexico, Tice, Connaught, Montreal, Phipps, Australia, Pasteur). The stronger induction of IL-12 and TNF-alpha in the presence of IFN-gamma was also observed by trehalose 6,6'-dimycolate (TDM) extracted from BCG-Japan than by TDM from BCG-Connaught, which lacks the methoxymycolate residue. These results suggest that 'early-shared strains' are more potent immunostimulating agents than 'late-shared strains', which could be attributed partially to methoxymycolate. Our study provides the basic information for immunological characterization of various BCG strains and may contribute to a re-evaluation of them as a reference strain for vaccination against tuberculosis.
The antiretroviral agent abacavir can cause hypersensitivity reaction (HSR) and the presence of HLA-B*57:01 is predictive of abacavir-HSR in Caucasian HIV-infected patients. However, abacavir-HSR also occurs in HLA-B*57:01 negative patients. In these patients, a safe diagnostic tool to dissect clinically suspected HSR against abacavir from adverse reactions against co-administered drugs is mandatory, and abacavir-ELISpot was evaluated. Peripheral blood mononuclear cells from 87 HIV patients were stimulated by abacavir and the production of interferon-? to the ELISpot was determined. Abacavir treated patients with HSR [confirmed (n=5) or suspected (n=12)] vs without HSR (n=42) displayed significantly higher numbers of abacavir-specific cells (82.3?23.0 or 10.5?4.5 vs -0.5?1.0 spot forming cells per million PBMC, p
Chlamydia trachomatis is one of the most widespread bacterial pathogens in the world that is transmitted sexually. Thereby a development of vaccine preparation for therapy and prophylaxis of infections caused by C. trachomatis is an actual topic of scientific research across the entire world. These vaccines could be used for both prophylaxis and therapy of already established chlamydia infection and, respectively, reduce the risk of chronic condition and prevent the spread of pathogen in the population. Features of chlamydia biology that are associated with obligate intracellular parasitism and immunopathologic state induced by this agent significantly complicate developments in this field. Currently a vaccine preparation that has reached clinical trials does not exist.
The narrow range of choice and virus resistance to the most common drugs require search and introduction of new drugs with proven efficacy and safety for the treatment of influenza. Ergoferon is a new combined medicine containing release active antibodies to interferon-gamma (anti-IFNgamma), CD4-coreceptor and histamine. The formulation influences various links of antiviral defense and provides antiinflammatory effect. The efficacy of the drug is related to its production process during which multiple reduction of the initial concentration of every component leads to release of special release activity. Previous experimental studies showed that anti-IFNgamma had antiviral activity against pandemic influenza virus A (H1N1) 2009 comparable to that ofoseltamivir (suppression of virus replication in the lung tissue, increase of the lifespan and reduction of the laboratory animals mortality). The aim of the multicentre randomized clinical trial was to compare (versus oseltamivir) the efficacy and safety of ergoferon in the treatment of influenza in adults. 213 patients with flu-like symptoms were examined in 8 medical centres of Russia during two epidemiological seasons (2010-11 and 2011-12). The inclusion criteria were: the first 48 hours after the onset; fever > or =37.8 degrees C, at least one common symptom and at least one respiratory symptom. Influenza was confirmed in 52 patients by QuickVue rapid diagnosis. 23 patients received ergoferon according to the treatment scheme and 29 received oseltamivir (daily dose 150 mg). Duration of the treatment was 5 days. The patients were followed up for 7 days. The primary endpoint was the percentage of the patients with the body temperature normalization for 2-5 days of the treatment. The maximum efficacy of ergoferon was observed on the second day of the treatment: almost half (48%) of the initially febrile patients had normal body temperature (versus 28% in the patients treated with oseltamivir). The comparison of the two groups of the patients by the morning and evening measurements of the body temperature every five days of the treatment by Cochran-Mantel-Haenszel revealed a significant difference between the two groups (chi2 = 7.1; p = 0.008). The average duration of the fever in the group of ergoferon was 2.3 +/- 1.2 days, in the group of oseltamivir--2.6 +/- 1.3 days (the efficacy of oseltamivir in the present study was comparable with the previously published data). The percentage of the patients treated with antipyretics because of hyperthermia on the second day of the treatment lowered 3 times and amounted to 17% (versus 41% in the oseltamivir group). The severity of common and respiratory symptoms (nose/throat/chest) significantly decreased on the third day of the treatment in both groups, the majority of the patients had either minimum severity or no signs of influenza. The clinical improvement was associated with positive changes in the life quality. No cases of the disease aggravation were recorded. Complications requiring antibiotic treatment or hospitalization were not observed during the followup. There were no adverse events recorded due to the drug use. No deviations in the laboratory indices were stated. Ergoferon is a new safe drug for the treatment of influenza. Its clinical efficacy was comparable to that of oseltamivir. The therapeutic effects of the drug were evident from: significant reduction of the disease severity, duration of febricity and general toxicity and respiratory flu symptoms, lower percentage of the patients with fever for 2 days. The febrile period in most of the patients did not exceed 2 days.
Experimental and computational evidence suggests that HLAs preferentially bind conserved regions of viral proteins, a concept we term "targeting efficiency," and that this preference may provide improved clearance of infection in several viral systems. To test this hypothesis, T-cell responses to A/H1N1 (2009) were measured from peripheral blood mononuclear cells obtained from a household cohort study performed during the 2009-2010 influenza season. We found that HLA targeting efficiency scores significantly correlated with IFN-? enzyme-linked immunosorbent spot responses (P = 0.042, multiple regression). A further population-based analysis found that the carriage frequencies of the alleles with the lowest targeting efficiencies, A*24, were associated with pH1N1 mortality (r = 0.37, P = 0.031) and are common in certain indigenous populations in which increased pH1N1 morbidity has been reported. HLA efficiency scores and HLA use are associated with CD8 T-cell magnitude in humans after influenza infection. The computational tools used in this study may be useful predictors of potential morbidity and identify immunologic differences of new variant influenza strains more accurately than evolutionary sequence comparisons. Population-based studies of the relative frequency of these alleles in severe vs. mild influenza cases might advance clinical practices for severe H1N1 infections among genetically susceptible populations.
Cites: N Engl J Med. 2009 Nov 12;361(20):1925-3419815860
Cites: Biochem Biophys Res Commun. 2009 Dec 18;390(3):349-5119769939
Cites: Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20365-7019918065
Cites: Euro Surveill. 2009;14(42). pii: 1936619883543
Cites: MMWR Morb Mortal Wkly Rep. 2009 Aug 28;58(33):913-819713879
Cites: MMWR Morb Mortal Wkly Rep. 2009 May 22;58(19):521-419478718
Cites: J Med Genet. 2009 Jul;46(7):469-7119429597
Cites: J Virol. 2009 Sep;83(18):9206-1419553306
Cites: J Virol. 2009 Jun;83(11):5485-9419297491
Cites: MMWR Morb Mortal Wkly Rep. 2009 Dec 11;58(48):1341-420010508
Influenza vaccination is generally recommended to hematopoietic stem cell transplant (HSCT) recipients. However, the seasonal subunit vaccination response is frequently suboptimal, and alternate more efficient vaccination systems must be examined. We compared the immunogenicity of an adjuvanted virosomal influenza and subunit vaccine in HSCT recipients.
The immunogenicity after a single dose (0.5 mL) of adjuvanted trivalent virosomal vaccination was evaluated in a study cohort of 21 HSCT recipients and compared to a control cohort of 30 HSCT recipients who received a single dose (0.5 mL) of non-adjuvanted seasonal trivalent subunit vaccination over 4 seasons from 2010 to 2014. Whole blood interferon-gamma (IFN-?) release assays were tested, both before and 30 days after vaccination, in response to influenza pandemic (pdm) H1N1, H3N2, and B antigens. HLA-A*02 dextramers, to gauge for the absolute number of antigen-specific CD8(+) T-cells, and pdm 2009 hemagglutinin inhibition (HI) assays, to test for neutralizing antibodies, were used as immunological readouts.
The pdm HI titers were poor in both cohorts with only 23% (5/21) after virosomal vaccination and 13.3% (4/30) in the seasonal vaccine cohort having protective titers (=40). The delta change of IFN-? production in response to influenza pdm H1N1 (P = 0.005) and influenza B antigens (P = 0.01) were significantly elevated in blood from individuals who received the virosomal as compared to the seasonal vaccine. The IFN-? response to pdm H1N1 was stronger (P 6 month post HSCT. We detected a significant increase in the frequency of matrix 1 (GILGFVTL) dextramer-specific CD8(+) T-cells after the virosomal vaccine (P = 0.01). No differences were seen in the hemagglutinin-specific CD8(+) T-cells between the 2 cohorts.
Vaccination using a virosomal delivery system is beneficial in eliciting robust cellular immune responses to pdm H1N1 influenza in SCT recipients.
This paper analyzes the data of examination and the results of the treatment of 25 patients aged over 80 years (mean age 68.5+/-7 years) suffering from varicosity with long nonhealing trophic ulcers of the distal limb segments (CVI CMP C6) and 20 patients of the same age groups with CVI CEAP stages 3-5. All patients with CVI underwent either full-scope phlebectomy (64.4%) or partial truncal phlebectomy (35.6%), in which the trunk of the greater saphenous vein was stripped up to the upper third of the leg. A TCM-3 outfit (RADIOmeter, Denmark) was employed to measure oxygen tension in limb tissues. Parameters of lipid peroxidation and antioxidant tissue defence were measured intraoperatively in the capillary blood of the fingers as well as in the venous blood withdrawn from the cubital vein and the greater saphenous vein in the lower third of the leg near ulcer). The data obtained evidenced that lipid peroxidation activity was most pronounced in the soft tissues of the lower third of the leg in the group of patients with remarkable chronic venous insufficiency without trophic venous ulcers (GVI CEAP C3-5) and was significantly depleted after formation of varicose ulcers (CVI CEAP C6) associated with remarkable tissue hypoxia (TepO2 1.7-7.0 mm Hg). In all patients with CVI, the syndrome of lipid peroxidation was associated with the lowering of antioxidant defence activity. Patients with trophic venous ulcers had the signs of active inflammation in the soft tissues of the leg. The data obtained in the course of the study made it possible to optimize the treatment policy for elderly patients with trophic venous ulcers. In addition to the lowering of venous hypertension, the treatment included correction of microcirculatory disorders related to local hypoxia. Of special importance was reperfusion attenuation in the postoperative period.
Screening with chest X-ray and the Mantoux test (the tuberculin skin test [TST]) is compulsory for adult asylum seekers who arrive in Norway. In 2005-2006, we included 823 asylum seekers in a study of the QuantiFERON-TB Gold test (QFT-G), and followed them for 23-32 months. Eight subjects with a positive and one with a negative QFT-G test were diagnosed with tuberculosis (TB). The positive (PPV) and negative predictive values (NPV) for TB were respectively 3.3% and 99.8%. The PPV was 2.3% and the NPV 99.1% for TST >or= 15 mm, and the NPV was 99.5% for TST >or= 6 mm in combination with a negative QFT-G.