Análisis del estado de inmunización de la población mayor de 65 años de Castilla y León frente al virus de la Gripe Aviar H5N1

1- Los valores en la protección previa a la vacuna de los distintos virus gripales endémicos españoles está en consonancia con su nivel de incidencia y relevancia en las epidemias anuales. 2- Los niveles de pre-protección de los distintos virus están en función de los acontecimientos epidémicos y de la gestión vacunal de las temporadas anteriores. 3- Los niveles de protección derivados de la vacunación siguen con respecto a los niveles de protección pre-vacunal un patrón evolutivo de tipo inverso. 4- El comportamiento relevante a protección vacunal es opuesto entre los virus de Gripe A y los de Gripe B, siguiendo un patrón que oscila en función de que linaje de Gripe B se incluya en la vacuna y de la relevancia en la presencia de Gripe B durante las epidemias anuales de Gripe A. Es por esto denotar la importancia que posee la puesta a punto y administración de la nueva vacuna tetravalente que posee los dos linajes de Gripe B. 5- La protección frente a la nueva variante H1N1pdm09 ha resultado muy rápida durante el periodo pandémico y durante la primera epidemia estacional producida por este virus. 6- Existe un porcentaje del 3,3% de la población mayor de 65 años en Castilla y León que posee anticuerpos capaces de reconocer específicamente proteína recombinante glicosilada del virus de la gripe aviar H5N1. 7- La presencia de estos anticuerpos en ausencia de circulación conocida del virus de la gripe aviar H5N1 por el territorio español se debe a un fenómeno de reactividad cruzada, que ha permitido al sistema inmune de los individuos positivos generar una respuesta de creación de anticuerpos capaces de reconocer este virus debido a fenómenos derivados de la exposición a infecciones naturales por otros virus gripales endémicos del territorio, y/o por las vacunaciones reiteradas a lo largo de su vida. 8- El fenómeno de reactividad cruzada se deriva de la compartición de epítopos específicos en zonas muy conservadas de la hemaglutinina de los virus de la gripe circulantes en España con respecto al virus de la gripe aviar H5N1. 9- La presencia de anticuerpos frente a H5N1 en la población anciana y no en la población joven-adulta e infantil se debe a un tiempo mucho mayor de exposición de los individuos mayores de 65 años a las infecciones naturales y a las vacunaciones.Departamento de Biología Celular, Histología y FarmacologíaMáster en Investigación en Ciencias de la Salu

Respuesta humoral específica y heteróloga frente a virus de la gripe en vacunados

Los virus de la gripe afectan anualmente al 10-20% de la población en los países occidentales, ocasionando epidemias anuales que suceden normalmente entre los meses de Enero y Marzo-Abril. La vacuna anual trivalente se administra varios meses antes del comienzo de la circulación de la gripe, y la formulación de la misma se realiza gracias a los datos remitidos desde los Centros Nacionales de Gripe sobre las cepas que se estima circulen en la siguiente temporada. Debido a que los virus de la gripe cambian de forma continua su composición genética, es importante evaluar el efecto que producen estas vacunas en la protección de la población a la que se administra. Varios son los grupos principales a los que se administra esta vacuna de forma preferente en nuestro país, denominados grupos de riesgo, como los ancianos, trabajadores de la sanidad y de la educación, embarazadas, inmunodeprimidos, etc. Los resultados de esta tesis mostraron que la vacunación trivalente anual induce una respuesta humoral heterotípica, que está relacionada con la distancia antigénica y genética existente entre los diversos subtipos de gripe que circulan estacionalmente y aquellos ya extintos, y con otros de carácter zoonótico que producen casos en humanos, como los virus de gripe aviar.Departamento de Anatomía Patológica, Microbiología, Medicina Preventiva y Salud Pública, Medicina Legal y ForenseDoctorado en Investigación en Ciencias de la Salu

Control de vibraciones en pasarelas peatonales

En los últimos años se ha construido un gran número de pasarelas peatonales como respuesta a la demanda de nuevas vías de paso en las ciudades. Estas estructuras tienen requisitos constructivos menos exigentes en comparación con otros tipos de puentes, lo cual ha facilitado el desarrollo de diseños con nuevos esquemas resistentes, complicadas geometrías y el empleo de nuevos materiales. En general estas estructuras son esbeltas, ligeras y poco amortiguadas, lo que en ocasiones ha generado problemas de vi-braciones al paso de peatones una vez puestas en servicio. Las normativas actuales son cada vez más sensibles a esta problemática, recomendando diseños cuyas frecuencias naturales deben estar alejadas de los rangos de frecuencia de paso típicos de los peatones y fijando límites de confort en forma de valores máximos de aceleración permitidos, asegurándose así un correcto comportamiento de la estructura. En el presente artículo se analiza esta problemática desde un punto de vista práctico. Para ello se muestran los puntos clave de las normativas y guías de diseño de pasarelas que se pueden encontrar actualmente en la bibliografía, se presentan las técnicas que habitualmente se emplean en el análisis dinámico experimental de estas estructuras, y se comentan las soluciones a las que generalmente se recurre para mejorar su comportamiento dinámico. Por último, se muestran los trabajos llevados a cabo por el Centro Tecnológico CARTIF en colaboración con las Universidades de Valladolid y Castilla-La Mancha en la pasarela peatonal del Museo de la Ciencia de Valladolid. Estos trabajos incluyen: (1) el estudio dinámico de los tres vanos metálicos de dicha pasarela, (2) el diseño e implementación de un amortiguador de masa sintonizado en el vano más sensible a las vibraciones, (3) la implementación de un amortiguador de masa activo utilizando un excitador electrodinámico, y (4) el desarrollo de pruebas para la verificación del estado de servicio de la pasarela. In the last years, a wide number of footbridges have been built as demand response of more direct pathways in cities. These structures have lower building requirements as compared with standard bridges. This circumstance has facilitated the development of new structural design with complex geometries and innovative materials. As a result, these structures may be slender, light and low damped, leading to vibration problems once in service. The current codes take into account this problem, and recommend designs with natural frequencies away from the typical pedestrian pacing rates and fix comfort limits to guarantee the serviceability of the structure.This paper studies this problem from a practical point of view. Thus, the key points of codes and footbridges guidelines are showed, the typical experimental dynamic analysis techniques are presented, and the usual solutions adopted to improve the dynamic performance of these structures are discussed. Finally, the works carried out on the Valladolid Science Museum Footbridge by Centro Tecnológico CARTIF in collaboration with the Universities of Valladolid and Castilla-La Mancha are showed. These works include: (1) the dynamic study of the three steel spans of the footbridge, (2) the design and implementation of a tuned mass damper in the liveliest span, (3) the implementation of an active mass damper using an electrodynamic shaker, and (4) the development of field tests to assess the serviceability of such span

Attitudes, perceptions and practices of influenza vaccination in the adult population: Results of a cross-sectional survey in Spain

Producción CientíficaIn Spain, the 2021/22 influenza season overlapped with the sixth wave of the 2019 coronavirus disease pandemic (COVID-19). Influenza is a major public health problem associated with high morbidity and mortality. The objectives of this study were to determine the knowledge, perceptions and practices of influenza vaccination in the Spanish population, coinciding with the COVID-19 pandemic, with special attention paid to people over 65 years of age. A cross-sectional study was carried out by conducting 2211 telephone interviews. It was observed that 81.6% of people ≥ 65 years were vaccinated annually or with some frequency compared to 35.5% of those under 65 years (p < 0.001). Fifty percent of Spaniards showed an intention to be vaccinated in the 2021/22 campaign, during the SARS-CoV2 pandemic. In the case of people ≥ 65 years old, this figure was 83% compared to 42% of those under 65 years old (p < 0.001). Significant predictors of intention to be vaccinated were age of 65 years or older (OR 1.8, 95% CI 1.3–2.5), female sex (OR 1.9, 95% CI 1.5–2.4), belonging to risk groups (OR 2.2, 95% CI 1.6–3.1) and having been previously vaccinated (OR 29.7, 95% CI 22.5–39.2). The main reasons for deciding to be vaccinated were the need to be protected against the virus and to be vaccinated annually. On the other hand, lack of recommendation and considering the influenza vaccine as not necessary were the main reasons for not getting vaccinated. In addition, health personnel stood out as the main source of information (32.9%) compared to traditional media (26.9%) and public administration (12.3%). This study aimed to assess and analyse the factors influencing willingness to receive influenza vaccines in the COVID-19 era among Spanish adults, as well as the main information channels and strategies to encourage vaccination

Impact of COVID-19 on adherence to treatment in patients with HIV

Producción CientíficaIn patients with human immunodeficiency virus (HIV), adherence to treatment is affected by the adverse effects of treatment, the presence of additional comorbidities, the complexity of dosage, and family and community support. However, one recent circumstance that was likely to have influenced therapeutic adherence was the COVID-19 pandemic and the applied containment measures. An observational retrospective study of a sample of patients with HIV was conducted to establish the relationship between sociodemographic, clinical, and pharmacological variables and therapeutic adherence before and after the pandemic. Adherence was measured using the validated simplified medication adherence questionnaire (SMAQ) and medication possession rate. A statistical analysis was performed to determine the mean, standard deviation, and median of the quantitative variables and the frequencies of the qualitative variables, and the relationship between the dependent and independent variables was analysed using the chi-squared test and Student’s t-test. No statistically significant differences were found between treatment adherence measured before and 22 months after the start of the pandemic. Sex, occupation, treatment regimen, viral load levels, and COVID-19 disease status did not influence adherence during either period. However, the age of patients with HIV had an impact on adherence during both periods (p = 0.008 and p = 0.002, respectively), with the age group under 45 years being less adherent. In addition, experiencing adverse drug reactions (ADRs) was shown to have an impact on adherence before the pandemic (p = 0.006) but not afterwards. The COVID-19 pandemic was not shown to have an impact on the degree of adherence to antiretroviral treatment in patients with HIV. Instead, adherence was influenced by patient age and ADR occurrence; therefore, measures must be taken in this regard. The SMAQ demonstrated sensitivity in assessing adherence

The impact of the COVID-19 pandemic on influenza vaccination attitudes and actions in Spain’s adult population

Producción CientíficaSeasonal influenza is an acute respiratory infection caused by the influenza virus which constitutes a significant public health issue associated with high morbidity and mortality. The aim of this study was to investigate changes in attitudes, perceptions, and practices regarding influenza vaccination in the Spanish adult population during the COVID-19 pandemic, as well as their vaccination intentions, with special attention paid to those over 65 years old and in high-risk groups. To this end, a cross-sectional study was conducted through 2219 telephone interviews, and the results were compared with results obtained a year earlier. Regarding the reasons for deciding to get vaccinated in the 2022/23 season, a significant increase was observed in vaccine confidence (36.7% vs. 42.8%), social responsibility (32.5% vs. 43.8%), and in awareness of the importance of vaccination due to COVID-19 (21.7% vs. 25.4%). Advanced age (OR 2.8, 95% CI 2.0–3.9), belonging to high-risk groups (OR 2.7, 95% CI 2.0–3.7), and prior vaccination (OR 25.3, 95% CI 19.5–32.7) emerged as significant predictors for the intent to receive the influenza vaccine in the 2022/23 season. Continuously observing shifts in perceptions and behaviors related to influenza immunization is crucial to pinpoint factors that may influence the willingness to receive the vaccine and, in this way, design public health strategies that achieve a greater acceptance of it

CRISPR/CasRx proof-of-concept for RNA degradation: A future tool against RNA viruses?

Producción CientíficaInfluenza viruses provide a great threat for the human population, causing highly contagious respiratory infections that can lead to serious clinical complications. There are a limited variety of influenza antivirals, and these antivirals are subjected to the constant emergence of resistances. Therefore, the development of new antiviral strategies to combat influenza viruses and other RNA viruses must be promoted. In this work, we design a proof-of-concept of a recently described CRISPR/Cas tool that has been proposed as a possible future RNA virus antiviral, named CRISPR/CasRx. For this, we verified the efficiency of the CasRx endonuclease in the degradation of the eGFP mRNA reporter gene and we established the best conditions for, and the efficient performance of, the CRISPR/CasRx system. The results were measured by fluorescence microscopy, flow cytometry, and qRT-PCR. The analyses demonstrated a reduction in fluorescence, regardless of the amount of eGFP reporter plasmid transfected. The analyses showed an 86–90% reduction in fluorescence by flow cytometry and a 51–80% reduction in mRNA expression by qRT-PCR. Our results demonstrate that the CasRx endonuclease is an efficient tool for eGFP mRNA knockdown. Therefore, subsequent experiments could be useful for the development of a new antiviral tool

Impaired antigen-specific B-cell responses after Influenza vaccination in kidney transplant recipients receiving co-stimulation blockade with Belatacept

Inhibidores de la calcineurina; Vacunación antigripal; Trasplante de riñónCalcineurin inhibitors; Influenza vaccination; Kidney transplantationInhibidors de la calcineurina; Vacunació antigripal; Trasplantament de ronyóEmerging data suggest that costimulation blockade with belatacept effectively controls humoral alloimmune responses. However, whether this effect may be deleterious for protective anti-infectious immunity remains poorly understood. We performed a mechanistic exploratory study in 23 kidney transplant recipients receiving either the calcineurin-inhibitor tacrolimus (Tac, n=14) or belatacept (n=9) evaluating different cellular immune responses after influenza vaccination such as activated T follicular Helper (Tfh), plasmablasts and H1N1 hemagglutinin (HA)-specific memory B cells (HA+mBC) by flow-cytometry, and anti-influenza antibodies by hemagglutination inhibition test (HI), at baseline and days 10, 30 and 90 post-vaccination. The proportion of CD4+CD54RA-CXCR5+ Tfh was lower in belatacept than Tac patients at baseline (1.86%[1.25-3.03] vs 4.88%[2.40-8.27], p=0.01) and remained stable post-vaccination. At M3, HA+mBc were significantly higher in Tac-treated patients (0.56%[0.32-1.49] vs 0.27%[0.13-0.44], p=0.04) and correlated with activated Tfh numbers. When stratifying patients according to baseline HA+mBc frequencies, belatacept patients with low HA+mBC displayed significantly lower HA+mBc increases after vaccination than Tac patients (1.28[0.94-2.4] vs 2.54[1.73-5.70], p=0.04). Also, belatacept patients displayed significantly lower seroprotection rates against H1N1 at baseline than Tac-treated patients (44.4% vs 84.6%) as well as lower seroconversion rates at days 10, 30 and 90 after vaccination (50% vs 0%, 63.6% vs 0%, and 63.6% vs 0%, respectively). We show the efficacy of belatacept inhibiting T-dependent antigen-specific humoral immune responses, active immunization should be highly encouraged before starting belatacept therapy.This work was supported by the Instituto de Salud Carlos III (ISCIII) (grant numbers ICI14/00242 and PI16/01321, PI19/01710) and by the European Union’s Horizon 2020 Research and innovation program (grant agreement 754995). Also, this work was partly supported by the SLT002/16/00183 grant, from the Department of Health of the Generalitat de Catalunya by the call “Accioí instrumental de programes derecerca orientats en l’àmbit de la recerca i la innovacioí en salut.” The authors thank the Research Centers of Catalonia (CERCA) Programme/Generalitat de Catalunya for institutional support. OB was awarded with an intensification grant from the “Instituto de Salud Carlos III” [INT19/00051]

Impaired antigen-specific B-cell responses after Influenza vaccination in kidney transplant recipients receiving co-stimulation blockade with Belatacept

Emerging data suggest that costimulation blockade with belatacept effectively controls humoral alloimmune responses. However, whether this effect may be deleterious for protective anti-infectious immunity remains poorly understood. We performed a mechanistic exploratory study in 23 kidney transplant recipients receiving either the calcineurin-inhibitor tacrolimus (Tac, n=14) or belatacept (n=9) evaluating different cellular immune responses after influenza vaccination such as activated T follicular Helper (Tfh), plasmablasts and H1N1 hemagglutinin (HA)-specific memory B cells (HA(+)mBC) by flow-cytometry, and anti-influenza antibodies by hemagglutination inhibition test (HI), at baseline and days 10, 30 and 90 post-vaccination. The proportion of CD4+CD54RA-CXCR5+ Tfh was lower in belatacept than Tac patients at baseline (1.86%[1.25-3.03] vs 4.88%[2.40-8.27], p=0.01) and remained stable post-vaccination. At M3, HA(+)mBc were significantly higher in Tac-treated patients (0.56%[0.32-1.49] vs 0.27%[0.13-0.44], p=0.04) and correlated with activated Tfh numbers. When stratifying patients according to baseline HA(+)mBc frequencies, belatacept patients with low HA(+)mBC displayed significantly lower HA(+)mBc increases after vaccination than Tac patients (1.28[0.94-2.4] vs 2.54[1.73-5.70], p=0.04). Also, belatacept patients displayed significantly lower seroprotection rates against H1N1 at baseline than Tac-treated patients (44.4% vs 84.6%) as well as lower seroconversion rates at days 10, 30 and 90 after vaccination (50% vs 0%, 63.6% vs 0%, and 63.6% vs 0%, respectively). We show the efficacy of belatacept inhibiting T-dependent antigen-specific humoral immune responses, active immunization should be highly encouraged before starting belatacept therapy