H1N1pdm09 Adjuvanted Vaccination in HIV-Infected Adults: A Randomized Trial of Two Single versus Two Double Doses

Since human immunodeficiency virus (HIV)-infected individuals are at increased risk of severe disease from pandemic influenza A (H1N1pdm09), vaccination was recommended as a prevention strategy. The aim of the present study was to evaluate the safety, immunogenicity and persistence of the immune response after vaccination against pandemic influenza A (H1N1pdm09) with an adjuvanted vaccine in human immunodeficiency virus (HIV)-infected adults using two single and two double doses.Open label, randomized trial to evaluate the immune response following H1N1pdm09 vaccination in HIV-infected participants compared to HIV-negative controls (NCT01155037). HIV-infected participants were randomized to receive 2 single (3.75 µg hemagglutinin) or 2 double (7.5 µg hemagglutinin) doses of the vaccine, 21 days apart. Controls received one dose of the vaccine. The primary endpoint was seroconversion as measured by hemagglutination inhibition assay. Two hundred fifty six HIV-infected participants (129 and 127 randomized to single and double doses, respectively) and 71 HIV-negative controls were enrolled. Among HIV-infected participants, seroconversion increased from 46.7% and 51.7% after the first dose to 77.2% and 83.8% after the second dose of the vaccine using single and double doses, respectively. Participants aged >40 years showed higher seroconversion compared to younger participants. Seroconversion among HIV-infected women and those with nadir CD4<200 cells/mm(3) was significantly higher with double doses. Persistence of protective antibodies six months after vaccination was achieved by 80% and 89.9% of the HIV-infected participants who received single and double doses, respectively.Our results support the recommendation of two double doses of adjuvanted H1N1pdm09 vaccine for HIV-infected individuals, particularly women, and those aged >40 years or with nadir CD4<200 cells/mm(3), to achieve antibody levels that are both higher and more sustained.ClinicalTrials.gov NCT01155037

Common Gene Therapy Viral Vectors Do Not Efficiently Penetrate Sputum from Cystic Fibrosis Patients

Norwalk virus and human papilloma virus, two viruses that infect humans at mucosal surfaces, have been found capable of rapidly penetrating human mucus secretions. Viral vectors for gene therapy of Cystic Fibrosis (CF) must similarly penetrate purulent lung airway mucus (sputum) to deliver DNA to airway epithelial cells. However, surprisingly little is known about the rates at which gene delivery vehicles penetrate sputum, including viral vectors used in clinical trials for CF gene therapy. We find that sputum spontaneously expectorated by CF patients efficiently traps two viral vectors commonly used in CF gene therapy trials, adenovirus (d∼80 nm) and adeno-associated virus (AAV serotype 5; d∼20 nm), leading to average effective diffusivities that are ∼3,000-fold and 12,000-fold slower than their theoretical speeds in water, respectively. Both viral vectors are slowed by adhesion, as engineered muco-inert nanoparticles with diameters as large as 200 nm penetrate the same sputum samples at rates only ∼40-fold reduced compared to in pure water. A limited fraction of AAV exhibit sufficiently fast mobility to penetrate physiologically thick sputum layers, likely because of the lower viscous drag and smaller surface area for adhesion to sputum constituents. Nevertheless, poor penetration of CF sputum is likely a major contributor to the ineffectiveness of viral vector based gene therapy in the lungs of CF patients observed to date

The N-P-K soil nutrient balance of portuguese cropland in the 1950s: the transition from organic to chemical fertilization

Agricultural nutrient balances have been receiving increasing attention in both historical and nutrient management research. The main objectives of this study were to further develop balance methodologies and to carry out a comprehensive assessment of the functioning and nutrient cycling of 1950s agroecosystems in Portugal. Additionally, the main implications for the history of agriculture in Portugal were discussed from the standpoint of soil fertility. We used a mass balance approach that comprises virtually all nitrogen (N), phosphorus (P) and potassium (K) inputs and outputs from cropland topsoil for average conditions in the period 1951–56. We found a consistent deficit in N, both for nationwide (−2.1 kg.ha−1.yr−1) and arable crops (−1.6 kg.ha−1.yr−1) estimates, that was rectified in the turn to the 1960 decade. P and K were, in contrast, accumulating in the soil (4.2–4.6 kg.ha−1.yr−1 and 1.0–3.0 kg.ha−1.yr−1, respectively). We observed that the 1950s is the very moment of inflection from an agriculture fertilized predominantly through reused N in biomass (livestock excretions plus marine, plant and human waste sources) to one where chemical fertilizers prevailed. It is suggested that N deficiency played an important role in this transitioninfo:eu-repo/semantics/publishedVersio