Evolución de la fisiopatía daño por sol a escaldado por sol durante la conservación refrigerada de manzanas

El daño por sol o asoleado de los frutos es un desorden fisiológico causado por radiación solar intensa en conjunto con altas temperaturas. Afecta la superficie de manzanas y peras reduciendo su calidad y posibilidad de comercialización. A nivel mundial, provoca importantes pérdidas económicas debido al descarte de fruta para exportación. En la región del Alto Valle de Río Negro se han determinado pérdidas entre el 30-50% según la especie y variedad y las condiciones climáticas de la temporada. En manzana se identificaron distintos niveles de daño por sol. El grado grave se corresponde con manchas bronceadas oscuras en la piel que pueden alcanzar la necrosis del tejido. El daño por sol moderado provoca en la superficie del fruto expuesta a la radiación solar un color amarillo intenso bronceado, mientras que aquellos con nivel leve presentan un tono amarillo claro o levemente decolorado en un sector de su piel (Figura 1). Los frutos con daño grave y moderado se descartan generalmente durante la operación de cosecha y, dependiendo del control y manejo realizado, ingresan a la planta de empaque en muy baja proporción. Los frutos con daño leve, conocido comúnmente como “reflejo de sol”, son considerados aptos para su comercialización, por lo cual es habitual encontrarlos durante el embalaje y la conservación refrigerada. Sin embargo, dependiendo del tiempo de almacenaje, estos frutos desarrollan un desorden fisiológico de poscosecha denominado escaldado por sol. Esta fisiopatía se visualiza como manchas marrones de diferente intensidad, exclusivamente en la superficie del fruto que estuvo expuesta a la radiación solar (Figura 2). Dicha característica disminuye considerablemente la calidad comercial de los frutos e incrementa en forma significativa el porcentaje de descarte durante el proceso de embalaje, en especial en variedades susceptibles como Granny Smith.EEA Alto ValleFil: Vita, Laura Inés. Universidad Nacional del Comahue. Facultad de Ciencias Agrarias; ArgentinaFil: Colavita, Graciela María. Universidad Nacional del Comahue. Facultad de Ciencias Agrarias; Argentin

High mobility group box 1 and tumor growth factor β: useful biomarkers in pediatric patients receiving peritoneal dialysis

AbstractBackground: Peritonitis, the most important limitation of peritoneal dialysis (PD), could be detected by biomarkers in dialysate effluent, representing a noninvasive method to indirectly assess the peritoneum status. The aim of our study was to test high mobility group box 1 (HMGB1) in PD patients, evaluating its role as precocious marker of peritoneum damage during peritonitis. Transforming growth factor (TGF)-β was correlated with peritoneal transport characteristics.Methods: Six patients, treated by ambulatory PD, were enrolled. Samples were collected at the onset of peritonitis (T1) and every day until its resolution (T-end). Serum (s) and peritoneal (p) white blood cell (WBC) count was also evaluated. Peritoneal Equilibration Test evaluated the filter activity of peritoneum.Results: In patients with acute peritonitis, the highest serum and peritoneal HMGB1 values (64 ± 3.6 and 70 ± 5.3 ng/mL, respectively) were assessed, with a progressive decrease of their levels at the resolution time (T-en..

Utility of Specific IgE to Ara h 2 in Italian Allergic and Tolerant Children Sensitized to Peanut

Emerging data suggest that measurement of serum IgE to peanut components can be clinically helpful and more accurate than IgE to whole peanut to predict peanut allergy. Not all studies have used prospective samples, multiple components and oral challenges. Currently, there are no data on this topic involving Italian children. 32 patients (23 males; median age 9 years) with reported history for peanut allergy and evidence of peanut sensitization (skin prick test to peanut extract ≥ 3mm) have been analyzed for serum IgE to whole peanut and recombinant allergen components Ara h 1, 2, 3, 8, and 9 with Immuno CAP and completed an open oral food challenge with peanut. 12 (37.5%) children had a positive challenge to peanut and were considered allergic. No differences were seen between the median values of IgE to peanut, Ara h 1, 3, 8 and 9 in allergic and tolerant children to peanut challenge. Noteworthy, 5 of 20 tolerant children had IgE to peanut> 15 kUA/l which is commonly considered a predictive value of peanut allergy. Conversely, a significant difference was seen when comparing the median value of IgE to Ara h 2 in the two groups: 0.75 kUA/l (IQR: 0.22-4.34 kUA/l) in allergic children versus 0.1 kUA/l (IQR: 0.1-0.12 kUA/l) in tolerant ones (P< 0.001). IgE levels to Ara h 2 are significantly higher in children that react to oral peanut challenge. Our findings in Italian children have been in line with recent reports in various populations of Northern Europe, the US and Australia and add confirmatory evidence that analysis of IgE to Ara h 2 could reduce the need for peanut challenge in suspected allergic patients

Evolución poscosecha del contenido de poliaminas libres en manzana var. Granny Smith con daño por sol

Las poliaminas (PAs) son policationes de bajo peso molecular que participan en la respuesta de protección de los tejidos vegetales sometidos a estrés oxidativo. El daño por sol en frutos es un desorden oxidativo causado por exposición a elevada radiación solar y temperatura. Esto origina disminución de productividad a campo y menor vida poscosecha, causando importantes pérdidas económicas. El objetivo del presente trabajo fue estudiar la evolución de PAs y el metabolismo oxidativo en piel de frutos de manzana var. Granny Smith con daño por sol durante la conservación refrigerada y su relación con el desarrollo de fisiopatías de poscosecha. Se trabajó con frutos con dos categorías de daño: sano (S) y daño leve (DS), sobre los cuales se realizaron determinaciones en cosecha, y luego de la conservación en frío convencional (0±1°C; HR 95%) por 90, 120, 150 y 180 días. Sobre la piel de cada sector se determinó: contenido de PAs, Putrescina (PUT), Espermidina (SPD) y Espermina (SPM), peroxidación de lípidos (TBARs) y capacidad antioxidante (DPPH). Durante la conservación se analizó la incidencia de escaldado de sol (ESol) y escaldado superficial (ESup). A cosecha DS presentó mayor contenido de PAs totales respecto a S. Sin embargo, durante la conservación refrigerada se registró un incremento de 28% de PAs en el tejido S respecto a DS debido exclusivamente al aumento de PUT, lo cual ha sido previamente indicado como unarespuesta de protección de los tejidos a las bajas temperaturas. SPD y SPM a cosecha fueron superiores 64% y 41% respectivamente en DS respecto a S y esta diferencia se mantuvo durante todo el período de almacenaje. El contenido de TBARs fue 59,8 nmol g-1PF en DS y 43,8 nmol g-1PF en S a cosecha, pero durante el almacenaje refrigerado se registró un incremento de 132% en S mientras que en DS se mantuvo constante. La capacidad antioxidante fue durante todo el período de conservación en promedio 48% en el tejido DS, mientras que en S 36%. La mayor capacidad antioxidante en el tejido DS podría atenuar el estrés por frío durante la conservación en cámara y el daño en membranas, lo cual explica que el contenido de TBARs se mantenga invariable en este tejido. A partir de los 90 días de conservación refrigerada se observó desarrollo de ESol sólo en el tejido DS mientras que la ESup se observó exclusivamente en tejido S. Estos resultados indican que la mayor capacidad antioxidante y contenido de SPD y SPM en el tejido DS no evitan el desarrollo de ESol. El estrés por frío en las condiciones de almacenamiento refrigerado en el tejido S promovió ESup que no pudo ser atenuada por el significativo aumento de PUT registrado en este tejido. Estos resultados contribuyen a ampliar la escasa información de la influencia de factores estresantes sobre el contenido de PAs en frutos de manzana.Fil: Vita, Laura Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigaciones en Toxicología Ambiental y Agrobiotecnología del Comahue. Universidad Nacional del Comahue. Facultad de Ciencias Agrarias. Centro de Investigaciones en Toxicología Ambiental y Agrobiotecnología del Comahue; ArgentinaFil: Spera, Nazarena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigaciones en Toxicología Ambiental y Agrobiotecnología del Comahue. Universidad Nacional del Comahue. Facultad de Ciencias Agrarias. Centro de Investigaciones en Toxicología Ambiental y Agrobiotecnología del Comahue; ArgentinaFil: Colavita, Graciela María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigaciones en Toxicología Ambiental y Agrobiotecnología del Comahue. Universidad Nacional del Comahue. Facultad de Ciencias Agrarias. Centro de Investigaciones en Toxicología Ambiental y Agrobiotecnología del Comahue; ArgentinaIV Congreso Argentino de Biología y Tecnología PoscosechaLa PlataArgentinaUniversidad Nacional de La Plata. Facultad de Ciencias Agrarias y Forestale

Maintenance of photosynthetic capacity in flooded tomato plants with reduced ethylene sensitivity

Ethylene is considered one of the most important plant hormones orchestrating plant responses to flooding stress. However, ethylene may induce deleterious effects on plants, especially when produced at high rates in response to stress. In this paper, we explored the effect of attenuated ethylene sensitivity in the Never ripe (Nr) mutant on leaf photosynthetic capacity of flooded tomato plants. We found out that reduced ethylene perception in Nr plants was associated with a more efficient photochemical and non-photochemical radiative energy dissipation capability in response to flooding. The data correlated with the retention of chlorophyll and carotenoids content in flooded Nr leaves. Moreover, leaf area and specific leaf area were higher in Nr, indicating that ethylene would exert a negative role in leaf growth and expansion under flooded conditions. Although stomatal conductance was hampered in flooded Nr plants, carboxylation activity was not affected by flooding in the mutant, suggesting that ethylene is responsible for inducing non-stomatal limitations to photosynthetic CO2 uptake. Upregulation of several cysteine protease genes and high protease activity led to Rubisco protein loss in response to ethylene under flooding. Reduction of Rubisco content would, at least in part, account for the reduction of its carboxylation efficiency in response to ethylene in flooded plants. Therefore, besides its role as a trigger of many adaptive responses, perception of ethylene entails limitations in light and dark photosynthetic reactions by speeding up the senescence process that leads to a progressive disassembly of the photosynthetic machinery in leaves of flooded tomato plants.Fil: de Pedro, Leandro Federico. Universidad Nacional de Formosa. Facultad de la Producción y El Medioambiente; ArgentinaFil: Mignolli, Francesco. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; ArgentinaFil: Scartazza, Andrea. Consiglio Nazionale delle Ricerche; ItaliaFil: Melana Colavita, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Bouzo, Carlos Alberto. Universidad Nacional del Litoral; ArgentinaFil: Vidoz, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; Argentin

Efecto de la aplicación de protectores solares a base de CaCO3 en la calidad de frutos de manzana

La elevada radiación solar promueve condiciones estresantes en plantas de manzana [Malus domestica (Suckow) Borkh.] que pueden ser atenuadas con el uso de protectores solares. Generalmente, su efecto se ha analizado mediante técnicas univariadas. El objetivo del presente estudio fue caracterizar, a través de un análisis estadístico multivariado, el efecto de protectores solares a base de CaCO3 en variables de calidad de manzanas ‘Braeburn’. El experimento se estableció bajo un diseño completamente aleatorizado con tres tratamientos (T=testigo, A=CaCO3, B=CaCO3+Zn) y cuatro repeticiones. Se aplicaron cuatro pulverizaciones: A, 2% p v -1 ; B, primera al 5% p v-1 y restantes al 2,5% p v-1. A cosecha se determinó grado de asoleado y, en frutos sanos, tamaño e índices de madurez. Se diferenciaron tres grupos (G). G1 constituido por individuos T, caracterizado por frutos de menor peso, mayor proporción de asoleado grave y madurez avanzada. G2 formado por individuos A y parte de T, con características intermedias entre G1 y G3. G3 formado por individuos B, con frutos de mayor peso, menor asoleado grave y menor madurez. El análisis multivariado permitió visualizar el efecto del CaCO3 sobre diversas variables de calidad simultáneamente. La aplicación de CaCO3 disminuyó el asoleado grave, aumentó el peso de los frutos y retrasó la madurez a cosecha. Es necesario profundizar en los mecanismos fisiológicos, bioquímicos y oxidativos involucrados en los efectos de las aplicaciones foliares de CaCO3 en frutos de manzana.High solar radiation promotes stress conditions in apple plants [Malus domestica (Suckow) Borkh.], which can be attenuated using sunburn suppressants products. Generally, the effect of sun protection agents has been analyzed using univariate techniques. The aim of the present study was to characterize, through multivariate statistical analysis, the effect of CaCO3- based sunburn suppressants on quality variables of 'Braeburn' apples. The experiment was conducted under a completely randomized design with three treatments (T=control, A=CaCO3, B=CaCO3+ZnO) and four replicates. Each treatment was sprayed four times: A, 2% w-1; B, 5% wv-1 for the first application and 2.5% w v-1 for the three remaining ones. At harvest, sunburn degree and, in nonaffected fruit, size and maturity indices were determined. Three groups (G) were distinguished. G1 consisted of T fruit and was characterized by lower fruit weight, more severe sun damage proportion of fruits, and an advanced maturity. G2 encompassed A and T fruit and showed intermediate characteristics between G1 and G3. G3 consisted of B fruit and showed higher weight, less severe sun damage, and lower maturity. Multivariate analysis allowed visualizing the effect of CaCO3- based formulations on fruit several quality variables simultaneously. We conclude that application of CaCO3 decreased severe sunburn, increased fruit weight, and delayed fruit maturity at harvest. Further research is needed to elucidate the physiological, biochemical and oxidative mechanisms mediating the effects of foliar CaCO3 applications on apple fruitFil: Jocou, Adriel Ian. Universidad Nacional del Comahue. Facultad de Ciencias Agrarias. Departamento de Biología Aplicada; Argentina.Fil: Muñoz Pérez, Martín. Universidad Nacional del Comahue. Facultad de Ciencias Agrarias. Departamento de Biología Aplicada; Argentina.Fil: Vita, Laura. Universidad Nacional del Comahue. Facultad de Ciencias Agrarias. Departamento de Biología Aplicada. Centro de Investigaciones en Toxicología Ambiental y Agrobiotecnología del Comahue; Argentina.Fil: Colavita, Graciela. Universidad Nacional del Comahue. Facultad de Ciencias Agrarias. Departamento de Biología Aplicada. Centro de Investigaciones en Toxicología Ambiental y Agrobiotecnología del Comahue; Argentina

La oferta regional e internacional de sidra: factores culturales, institucionales y socio económicos

Las exigencias de los mercados sobre el negocio frutícola de la Norpatagonia han derivado en un aumento del descarte de pera y manzana, que alcanza el 30 y 40 %, respectivamente. Los bajos precios pagados por la industria obligan al sector a repensar sus estrategias para mejorar su rentabilidad con el aumento del valor agregado de la fruta de descarte. En otros países la industria sidrera se vincula al desarrollo regional- España, Gran Bretaña, Estados Unidos- las preguntas a responder son:¿qué factores han frenado el desarrollo de la industria regional de sidra?,¿cuál es actualmente su posición competitiva?, y ¿en qué aspectos se debe focalizar para potenciar su crecimiento, de manera que contribuya al desarrollo regional? El propósito de esta investigación es analizar la oferta regional de sidra y compararla con la oferta de otras regiones, especialmente donde la industria sidrera ha contribuido al desarrollo local. Para esto se utilizará como base teórica el modelo del diamante de Porter, propuesto para explicar la ventaja competitiva de un agrupamiento productivo, a través de cuatro determinantes, influenciados por el gobierno y la casualidad: condiciones de los factores, de la demanda, sectores conexos y auxiliares, y estrategia, y estructura y rivalidad de la empresa.Market demands on the fruit business in Northern Patagonia have led into the increase of second quality fruit (availability/production), approximately 30% of pears and 40% of apples. Low industry prices make it necessary to re think strategies to improve profitability with the rise of value added to second quality fruit. In other countries cider industry is linked to regional development – Spain, Great Britain, United States of America. The questions to answer are: what are the factors which have slowed down regional cider industry development? What is its current competitive position? What aspects have to be highlighted to boost its growth in order to contribute to regional development? The aim of this research is to analyze regional cider offer and make a comparison with other regions, particularly where cider industry has contributed to local development. With this purpose in mind, Porter’s diamond model is used as a theoretical basis in order to explain the competitive advantage of a productive group throughout four government and chance influenced determinants: demand factor conditions, auxiliary and related sector, strategy, structure and company rivalry.EEA Alto ValleFil: Villarreal, Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Alto Valle; ArgentinaFil: Pedreschi, Romina. Universidad Nacional del Comahue. Facultad de Ciencias y Tecnología de los Alimentos; ArgentinaFil: Reissig, Joaquin. Universidad Nacional del Comahue. Facultad de Ciencias Agrarias; ArgentinaFil: Malaspina, María Laura. Universidad Nacional del Comahue. Facultad de Ciencias y Tecnología de los Alimentos; ArgentinaFil: Colavita, Carlos. Universidad Nacional del Comahue. Facultad de Ciencias Agrarias; Argentin

Constraining Exoplanet Metallicities and Aerosols with ARIEL: An Independent Study by the Contribution to ARIEL Spectroscopy of Exoplanets (CASE) Team

Launching in 2028, ESA's Atmospheric Remote-sensing Exoplanet Large-survey (ARIEL) survey of $\sim$1000 transiting exoplanets will build on the legacies of Kepler and TESS and complement JWST by placing its high precision exoplanet observations into a large, statistically-significant planetary population context. With continuous 0.5--7.8~$\mu$m coverage from both FGS (0.50--0.55, 0.8--1.0, and 1.0--1.2~$\mu$m photometry; 1.25--1.95~$\mu$m spectroscopy) and AIRS (1.95--7.80~$\mu$m spectroscopy), ARIEL will determine atmospheric compositions and probe planetary formation histories during its 3.5-year mission. NASA's proposed Contribution to ARIEL Spectroscopy of Exoplanets (CASE) would be a subsystem of ARIEL's FGS instrument consisting of two visible-to-infrared detectors, associated readout electronics, and thermal control hardware. FGS, to be built by the Polish Academy of Sciences' Space Research Centre, will provide both fine guiding and visible to near-infrared photometry and spectroscopy, providing powerful diagnostics of atmospheric aerosol contribution and planetary albedo, which play a crucial role in establishing planetary energy balance. The CASE team presents here an independent study of the capabilities of ARIEL to measure exoplanetary metallicities, which probe the conditions of planet formation, and FGS to measure scattering spectral slopes, which indicate if an exoplanet has atmospheric aerosols (clouds and hazes), and geometric albedos, which help establish planetary climate. Our design reference mission simulations show that ARIEL could measure the mass-metallicity relationship of its 1000-planet single-visit sample to $>7.5\sigma$ and that FGS could distinguish between clear, cloudy, and hazy skies and constrain an exoplanet's atmospheric aerosol composition to $>5\sigma$ for hundreds of targets, providing statistically-transformative science for exoplanet atmospheres.Comment: accepted to PASP; 23 pages, 6 figure

Immunogenicity and reactogenicity of modified vaccinia Ankara pre-exposure vaccination against mpox according to previous smallpox vaccine exposure and HIV infection: prospective cohort study

BACKGROUND: Pre-exposure vaccination with MVA-BN has been widely used against mpox to contain the 2022 outbreak. Many countries have defined prioritized strategies, administering a single dose to those historically vaccinated for smallpox, to achieve quickly adequate coverage in front of low supplies. Using epidemiological models, real-life effectiveness was estimated at approximately 36%–86%, but no clinical trials were performed. Few data on MVA-BN immunogenicity are currently available, and there are no established correlates of protection. Immunological response in PLWH in the context of the 2022 outbreak was also poorly described. METHODS: Blood samples were collected from participants eligible for pre-exposure MVA-BN vaccination before (T1) receiving a full course of vaccine (single-dose for vaccine-experienced or smallpox-primed and two-dose for smallpox vaccine-naïve or smallpox non-primed) and one month after the last dose (T2 and T3, respectively). MPXV-specific IgGs were measured by in-house immunofluorescence assay, using 1:20 as screening dilution, MPXV-specific nAbs by 50% plaque reduction neutralization test (PRNT50, starting dilution 1:10), and IFN-γ-producing specific T cells to MVA-BN vaccine, by ELISpot assay. Paired or unpaired t-test and Wilcoxon or Mann–Whitney test were used to analyse IgG and nAbs, and T-cell response, as appropriate. The probability of IgG and nAb response in vaccine-experienced vs. vaccine-naïve was estimated in participants not reactive at T1. The McNemar test was used to evaluate vaccination's effect on humoral response both overall and by smallpox vaccination history. In participants who were not reactive at T1, the proportion of becoming responders one month after full-cycle completion by exposure groups was compared by logistic regression and then analysed by HIV status strata (interaction test). The response was also examined in continuous, and the Average Treatment Effect (ATE) of the difference from baseline to schedule completion according to previous smallpox vaccination was estimated after weighting for HIV using a linear regression model. Self-reports of adverse effects following immunization (AEFIs) were prospectively collected after the first MVA-BN dose (T1). Systemic (S-AEFIs: fatigue, myalgia, headache, GI effects, chills) and local (L-AEFIs: redness, swelling, pain) AEFIs were graded as absent (grade 0), mild (1), moderate (2), or severe (3). The maximum level of severity for S-AEFIs and L-AEFIs ever experienced over the 30 days post-dose by vaccination exposure groups were analysed using a univariable multinomial logistic regression model and after adjusting for HIV status; for each of the symptoms, we also compared the mean duration by exposure group using an unpaired t-test. FINDING: Among the 164 participants included, 90 (54.8%) were smallpox vaccine-experienced. Median age was 49 years (IQR 41–55). Among the 76 (46%) PLWH, 76% had a CD4 count >500 cells/μL. There was evidence that both the IgG and nAbs titers increased after administration of the MVA-BN vaccine. However, there was no evidence for a difference in the potential mean change in humoral response from baseline to the completion of a full cycle when comparing primed vs. non-primed participants. Similarly, there was no evidence for a difference in the seroconversion rate after full cycle vaccination in the subset of participants not reactive for nAbs at T1 (p = 1.00 by Fisher's exact test). In this same analysis and for the nAbs outcome, there was some evidence of negative effect modification by HIV (interaction p-value = 0.17) as primed people living with HIV (PLWH) showed a lower probability of seroconversion vs. non-primed, and the opposite was seen in PLWoH. When evaluating the response in continuous, we observed an increase in T-cell response after MVA-BN vaccination in both primed and non-primed. There was evidence for a larger increase when using the 2-dose vs. one-dose strategy with a mean difference of −2.01 log2 (p ≤ 0.0001), after controlling for HIV. No evidence for a difference in the risk of developing any AEFIs of any grade were observed by exposure group, except for the lower risk of grade 2 (moderate) fatigue, induration and local pain which was lower in primed vs. non-primed [OR 0.26 (0.08–0.92), p = 0.037; OR 0.30 (0.10–0.88), p = 0.029 and OR 0.19 (0.05–0.73), p = 0.015, respectively]. No evidence for a difference in symptom duration was also detected between the groups. INTERPRETATION: The evaluation of the humoral and cellular response one month after the completion of the vaccination cycle suggested that MVA-BN is immunogenic and that the administration of a two-dose schedule is preferable regardless of the previous smallpox vaccination history, especially in PLWH, to maximize nAbs response. MVA-BN was safe as well tolerated, with grade 2 reactogenicity higher after the first administration in vaccine-naïve than in vaccine-experienced individuals, but with no evidence for a difference in the duration of these adverse effects. Further studies are needed to evaluate the long-term duration of immunity and to establish specific correlates of protection

Immunogenicity and reactogenicity of modified vaccinia Ankara pre-exposure vaccination against mpox according to previous smallpox vaccine exposure and HIV infection. Prospective cohort study

Background: Pre-exposure vaccination with MVA-BN has been widely used against mpox to contain the 2022 outbreak. Many countries have defined prioritized strategies, administering a single dose to those historically vaccinated for smallpox, to achieve quickly adequate coverage in front of low supplies. Using epidemiological models, real-life effectiveness was estimated at approximately 36%-86%, but no clinical trials were performed. Few data on MVA-BN immunogenicity are currently available, and there are no established correlates of protection. Immunological response in PLWH in the context of the 2022 outbreak was also poorly described. Methods: Blood samples were collected from participants eligible for pre-exposure MVA-BN vaccination before (T1) receiving a full course of vaccine (single-dose for vaccine-experienced or smallpox-primed and two-dose for smallpox vaccine-naïve or smallpox non-primed) and one month after the last dose (T2 and T3, respectively). MPXV-specific IgGs were measured by in-house immunofluorescence assay, using 1:20 as screening dilution, MPXV-specific nAbs by 50% plaque reduction neutralization test (PRNT50, starting dilution 1:10), and IFN-γ-producing specific T cells to MVA-BN vaccine, by ELISpot assay. Paired or unpaired t-test and Wilcoxon or Mann-Whitney test were used to analyse IgG and nAbs, and T-cell response, as appropriate. The probability of IgG and nAb response in vaccine-experienced vs. vaccine-naïve was estimated in participants not reactive at T1. The McNemar test was used to evaluate vaccination's effect on humoral response both overall and by smallpox vaccination history. In participants who were not reactive at T1, the proportion of becoming responders one month after full-cycle completion by exposure groups was compared by logistic regression and then analysed by HIV status strata (interaction test). The response was also examined in continuous, and the Average Treatment Effect (ATE) of the difference from baseline to schedule completion according to previous smallpox vaccination was estimated after weighting for HIV using a linear regression model. Self-reports of adverse effects following immunization (AEFIs) were prospectively collected after the first MVA-BN dose (T1). Systemic (S-AEFIs: fatigue, myalgia, headache, GI effects, chills) and local (L-AEFIs: redness, swelling, pain) AEFIs were graded as absent (grade 0), mild (1), moderate (2), or severe (3). The maximum level of severity for S-AEFIs and L-AEFIs ever experienced over the 30 days post-dose by vaccination exposure groups were analysed using a univariable multinomial logistic regression model and after adjusting for HIV status; for each of the symptoms, we also compared the mean duration by exposure group using an unpaired t-test. Findings: Among the 164 participants included, 90 (54.8%) were smallpox vaccine-experienced. Median age was 49 years (IQR 41-55). Among the 76 (46%) PLWH, 76% had a CD4 count &gt;500&nbsp;cells/μL. There was evidence that both the IgG and nAbs titers increased after administration of the MVA-BN vaccine. However, there was no evidence for a difference in the potential mean change in humoral response from baseline to the completion of a full cycle when comparing primed vs. non-primed participants. Similarly, there was no evidence for a difference in the seroconversion rate after full cycle vaccination in the subset of participants not reactive for nAbs at T1 (p&nbsp;=&nbsp;1.00 by Fisher's exact test). In this same analysis and for the nAbs outcome, there was some evidence of negative effect modification by HIV (interaction p-value&nbsp;=&nbsp;0.17) as primed people living with HIV (PLWH) showed a lower probability of seroconversion vs. non-primed, and the opposite was seen in PLWoH. When evaluating the response in continuous, we observed an increase in T-cell response after MVA-BN vaccination in both primed and non-primed. There was evidence for a larger increase when using the 2-dose vs. one-dose strategy with a mean difference of&nbsp;-2.01 log2 (p ≤ 0.0001), after controlling for HIV. No evidence for a difference in the risk of developing any AEFIs of any grade were observed by exposure group, except for the lower risk of grade 2 (moderate) fatigue, induration and local pain which was lower in primed vs. non-primed [OR 0.26 (0.08-0.92), p&nbsp;=&nbsp;0.037; OR 0.30 (0.10-0.88), p&nbsp;=&nbsp;0.029 and OR 0.19 (0.05-0.73), p&nbsp;=&nbsp;0.015, respectively]. No evidence for a difference in symptom duration was also detected between the groups. Interpretation: The evaluation of the humoral and cellular response one month after the completion of the vaccination cycle suggested that MVA-BN is immunogenic and that the administration of a two-dose schedule is preferable regardless of the previous smallpox vaccination history, especially in PLWH, to maximize nAbs response. MVA-BN was safe as well tolerated, with grade 2 reactogenicity higher after the first administration in vaccine-naïve than in vaccine-experienced individuals, but with no evidence for a difference in the duration of these adverse effects. Further studies are needed to evaluate the long-term duration of immunity and to establish specific correlates of protection. Funding: The study was supported by the National Institute for Infectious Disease Lazzaro Spallanzani IRCCS "Advanced grant 5&nbsp;×&nbsp;1000, 2021" and by the Italian Ministry of Health "Ricerca Corrente Linea 2"