23 research outputs found

    Trivalent Adenovirus Type 5 HIV Recombinant Vaccine Primes for Modest Cytotoxic Capacity That Is Greatest in Humans with Protective HLA Class I Alleles

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    If future HIV vaccine design strategies are to succeed, improved understanding of the mechanisms underlying protection from infection or immune control over HIV replication remains essential. Increased cytotoxic capacity of HIV-specific CD8+ T-cells associated with efficient elimination of HIV-infected CD4+ T-cell targets has been shown to distinguish long-term nonprogressors (LTNP), patients with durable control over HIV replication, from those experiencing progressive disease. Here, measurements of granzyme B target cell activity and HIV-1-infected CD4+ T-cell elimination were applied for the first time to identify antiviral activities in recipients of a replication incompetent adenovirus serotype 5 (Ad5) HIV-1 recombinant vaccine and were compared with HIV-negative individuals and chronically infected patients, including a group of LTNP. We observed readily detectable HIV-specific CD8+ T-cell recall cytotoxic responses in vaccinees at a median of 331 days following the last immunization. The magnitude of these responses was not related to the number of vaccinations, nor did it correlate with the percentages of cytokine-secreting T-cells determined by ICS assays. Although the recall cytotoxic capacity of the CD8+ T-cells of the vaccinee group was significantly less than that of LTNP and overlapped with that of progressors, we observed significantly higher cytotoxic responses in vaccine recipients carrying the HLA class I alleles B*27, B*57 or B*58, which have been associated with immune control over HIV replication in chronic infection. These findings suggest protective HLA class I alleles might lead to better outcomes in both chronic infection and following immunization due to more efficient priming of HIV-specific CD8+ T-cell cytotoxic responses

    Anales de Edafología y Agrobiología Tomo 43 Número 7-8

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    Suelos. Edafoclinas de la vertiente sur-suroeste de la Sierra Nevada, por R. Delgado Calvo-Flores y E. Ortega Bernaldo de Quiros.-- Estudio sobre muestras de suelo humectadas por imbibición. l. Evaporación y movimiento del agua, por F. lngelmo Sánchez y S. Cuadrado Sánchez.-- Estudios sobre muestras de suelos humectadas por imbibición. II. Evaporación y redistribución del agua, por F. Ingelmo Sanchez y S. Cuadrado Sánchez.-- Suelos de la zona húmeda española X. Suelos sobre sepertinas. X. Mineralogía, por M. l. López,F. Macías, C. Garcia Paz y F. Guitián Ojea.-- Aplicación del sistema Riquier-Fao a la cartografía de suelos de la zona de Linares (Hoja topográfica a escala 1 50000, 905), por G. Delgado CalvoFlores y J. Aguilar Ruiz.-- Aplicación de métodos paramétricos a la evaluación dé la aptitud para uso agrícola de los suelos, de la zona de Linares (Hoja topográfica a escala 1 50000, 905), por G. Delgado Calvo-Flores y J. Aguilar Ruiz.-- Características físico-Químicas de la turbera de Vivero (Lugo), por A. Molinero, A. Polo y E. Dorado.-- Nutrición y Fisiología Vegetal. Determinación de Boro en jugos de tejidos conductores, por A. Gárate, R. O. Carpena Ruiz y A. M. Ramón.-- Evaluación de calcio, magnesio, potasio y sodio en disoluciones nutritivas y plantas mediante electrodos selectivos de iones, por M. J. Sarro, C. Cadahia, A. Masaguer y J. Peñalosa,.--Aplicaciones de los electrodos sensibles a F-y Pb2+ en análisis agrícolas. Determinaciones directas e indirectas (Sulfatos y fosfatos), por M. J. Sarro; O. Carpena; C. Cadahia y M. L. García.-- Aceites esenciales en hojas de variedades de limonero (Citrus limon L. Burm. f.), por Melendreras, F. A., Laencina, J., Flores, J. y Guzman, G.-- Efecto de la interacción salinidad de sulfatos-fertilización nitrogenada en el cultivo de tomate (Lycopersicum Esculentum Mili), por Martínez, V.; A. Cerdá; F. G. Fernández y M. Caro.-- Efectividad de complejos orgánicos de hierro en la corrección de la clorosis férrica del limonero, por E. Hellín, R. Ureña, F. Sevilla y S. Llorente.-- Control fitosanitario de las poblaciones del acaro de las maravillas (Aceria sheldoni Ewing), por Ortuño, A., Abrisqueta, J. Mª; Gómez, J. y Hernánsaez, A.-- Efecto de la interacción salinidad del sulfato-fertilidad fosfarada en el cultivo de tomate (Lycopersicum Esculetum, Mili), por Martínez, V., Caro, M.; Cerdá, A. y Fernández, F. G. Fertilidad del Suelo. Characterization of the organic fraction of cattle slurry. II. Fundamental carbon-bearing compounds and distribution of nitrogen, by González Prieto, S. J., Carballas, M. and Carballas, T.-- Nota previa. First results on the effect of the number of stages on the hydrolytic analysis, of the distribution of nitrogenated organic compounds in cattle slurry, by González-Prieto, S. J.; Carballas, M. and Carballas, T.-- Bibliografía.-- NotasPeer reviewe

    Complicating infectious foci in patients with Staphylococcus aureus or Streptococcus species bacteraemia.

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    Contains fulltext : 53587.pdf (publisher's version ) (Closed access)Complicating infectious foci resulting from haematogenous or local spread of microorganisms are observed frequently in patients with Staphylococcus aureus bacteraemia (SAB) or Streptococcus species bacteraemia (SSB). The aim of this study was to compare the epidemiology of complicating infectious foci during SAB and SSB in a university hospital in The Netherlands. The charts of all adult patients diagnosed with SAB or SSB (except for Streptococcus pneumoniae bacteraemia) from July 2002 until December 2004 were reviewed retrospectively. Overall, 180 immunocompetent patients were identified, 127 with SAB and 53 with SSB. The percentage of patients with complicating infectious foci (39% of SAB patients, 25% of SSB patients) did not differ significantly between the groups. Endocarditis and cerebral involvement, however, were significantly more common in the SSB group. Of all complicating infectious foci, 32% lacked guiding signs or symptoms and 10% were detected only at autopsy. Factors associated with the development of complicating infectious foci were a delay in treatment for more than 48 h after the onset of symptoms, community acquisition, persistently positive blood cultures, congenital heart disease, and the presence of foreign bodies or prosthetic valves. Infection-related mortality was 18% in SAB patients and 11% in SSB patients and was significantly higher in patients with complicating infectious foci (29 vs. 9%). In conclusion, complicating infectious foci develop in approximately one-third of all patients with SAB and SSB. An active approach that entails searching for the complicating infectious foci is warranted in these patients, because only two-thirds of complicated infectious foci have guiding symptoms or signs, and infection-related mortality is significantly increased in patients with complicating infectious foci compared to patients without these infections.9 p

    The HIV/AIDS Vaccine Candidate MVA-B Administered as a Single Immunogen in Humans Triggers Robust, Polyfunctional, and Selective Effector Memory T Cell Responses to HIV-1 Antigens ▿ ‡

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    Attenuated poxvirus vectors expressing human immunodeficiency virus type 1 (HIV-1) antigens are considered promising HIV/AIDS vaccine candidates. Here, we describe the nature of T cell immune responses induced in healthy volunteers participating in a phase I clinical trial in Spain after intramuscular administration of three doses of the recombinant MVA-B-expressing monomeric gp120 and the fused Gag-Pol-Nef (GPN) polyprotein of clade B. The majority (92.3%) of the volunteers immunized had a positive specific T cell response at any time postvaccination as detected by gamma interferon (IFN-γ) intracellular cytokine staining (ICS) assay. The CD4+ T cell responses were predominantly Env directed, whereas the CD8+ T cell responses were similarly distributed against Env, Gag, and GPN. The proportion of responders after two doses of MVA-B was similar to that obtained after the third dose of MVA-B vaccination, and the responses were sustained (84.6% at week 48). Vaccine-induced CD8+ T cells to HIV-1 antigens after 1 year were polyfunctional and distributed mainly within the effector memory (TEM) and terminally differentiated effector memory (TEMRA) T cell populations. Antivector T cell responses were mostly induced by CD8+ T cells, highly polyfunctional, and of TEMRA phenotype. These findings demonstrate that the poxvirus MVA-B vaccine candidate given alone is highly immunogenic, inducing broad, polyfunctional, and long-lasting CD4 and CD8 T cell responses to HIV-1 antigens, with preference for TEM. Thus, on the basis of the immune profile of MVA-B in humans, this immunogen can be considered a promising HIV/AIDS vaccine candidate

    Safety and immunogenicity of a modified vaccinia ankara-based HIV-1 vaccine (MVA-B) in HIV-1-infected patients alone or in combination with a drug to reactivate latent HIV-1

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    Objectives: The safety, immunogenicity, impact on the latent reservoir and rebound of viral load after therapeutic HIV-1 vaccination with recombinant modified vaccinia Ankara-based (MVA-B) HIV-1 vaccine expressing monomeric gp120 and the fused Gag-Pol-Nef polyprotein of clade B with or without a drug to reactivate latent HIV-1 (disulfiram) were assessed. Methods: HIV-1-infected patients were randomized to receive three injections of MVA-B (n¼20) or placebo (n¼10). Twelve patients (eight who received vaccine and four who were given placebo) received a fourth dose of MVA-B followed by 3 months of disulfiram. Combined ART (cART) was discontinued 8 weeks after the last dose of MVA-B. Clinical Trials.gov identifier: NCT01571466. Results: MVA-B was safe and well tolerated. A minor, but significant, increase in the T cell responses targeting vaccine inserts of Gag was observed [a median of 290, 403 and 435 spot-forming-cells/106 PBMCs at baseline, after two vaccinations and after three vaccinations, respectively; P¼0.02 and P¼0.04]. After interruption of cART, a modest delay in the rebound of the plasma viral load in participants receiving vaccine but not disulfiram was observed compared with placebo recipients (P¼0.01). The dynamics of the viral load rebound did not change in patients receiving MVA-B/disulfiram. No changes in the proviral reservoir were observed after disulfiram treatment. Conclusions: MVA-B vaccination was a safe strategy to increase Gag-specific T cell responses in chronically HIV-1- infected individuals, but it did not have a major impact on the latent reservoir or the rebound of plasma viral load after interruption of cART when given alone or in combination with disulfiram
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