High-dimensional analysis of 16 SARS-CoV-2 vaccine combinations reveals lymphocyte signatures correlating with immunogenicity

The range of vaccines developed against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) provides a unique opportunity to study immunization across different platforms. In a single-center cohort, we analyzed the humoral and cellular immune compartments following five coronavirus disease 2019 (COVID-19) vaccines spanning three technologies (adenoviral, mRNA and inactivated virus) administered in 16 combinations. For adenoviral and inactivated-virus vaccines, heterologous combinations were generally more immunogenic compared to homologous regimens. The mRNA vaccine as the second dose resulted in the strongest antibody response and induced the highest frequency of spike-binding memory B cells irrespective of the priming vaccine. Priming with the inactivated-virus vaccine increased the SARS-CoV-2-specific T cell response, whereas boosting did not. Distinct immune signatures were elicited by the different vaccine combinations, demonstrating that the immune response is shaped by the type of vaccines applied and the order in which they are delivered. These data provide a framework for improving future vaccine strategies against pathogens and cancer

EXPERIENCIAS DE INVESTIGACIÓN EN CIENCIAS SOCIALES Y HUMANIDADES

Resultados de las intervenciones en las Jornadas de tesistas y estudiantes de posgrado en ciencias sociales realizadas en la ciudad de Córdoba en el año 2015

Centros de escritura universitarios: una estrategia para la permanencia estudiantil

PublishedLas universidades colombianas han sido precursoras en la creación de centros y programas de escritura en Latinoamérica, así como en la producción y difusión de estudios sobre su labor. No es casual, entonces, que la iniciativa para la publicación de un nuevo libro haya surgido en el ámbito académico colombiano. Gracias a la convocatoria del Centro de Escritura, Lectura y Oralidad Académica de la Universidad Santiago de Cali (CELOA) nació Centros de escritura universitarios: Una estrategia para la permanencia estudiantil, un libro que reúne investigaciones llevadas a cabo por cinco centros de escritura de universidades colombianas. El título se nutre de la experiencia y de los trabajos de investigadores que desde hace décadas vienen aportando y reflexionando sobre la importancia de la escritura y la lectura para la construcción del saber y la comunicación de ideas. Entre las contribuciones más citadas por los autores de los capítulos se encuentran las de Paula Carlino, quien en su libro Escribir, leer y aprender en la universidad (Fondo de Cultura Económica, 2005) introdujo el concepto de “alfabetización académica”, que ha sido fundamental para desarrollar prácticas y profundizar en los estudios sobre la enseñanza terciaria

IL-17RA Signaling Reduces Inflammation and Mortality during Trypanosoma cruzi Infection by Recruiting Suppressive IL-10-Producing Neutrophils

Members of the IL-17 cytokine family play an important role in protection against pathogens through the induction of different effector mechanisms. We determined that IL-17A, IL-17E and IL-17F are produced during the acute phase of T. cruzi infection. Using IL-17RA knockout (KO) mice, we demonstrate that IL-17RA, the common receptor subunit for many IL-17 family members, is required for host resistance during T. cruzi infection. Furthermore, infected IL-17RA KO mice that lack of response to several IL-17 cytokines showed amplified inflammatory responses with exuberant IFN-γ and TNF production that promoted hepatic damage and mortality. Absence of IL-17RA during T. cruzi infection resulted in reduced CXCL1 and CXCL2 expression in spleen and liver and limited neutrophil recruitment. T. cruzi-stimulated neutrophils secreted IL-10 and showed an IL-10-dependent suppressive phenotype in vitro inhibiting T-cell proliferation and IFN-γ production. Specific depletion of Ly-6G+ neutrophils in vivo during T. cruzi infection raised parasitemia and serum IFN-γ concentration and resulted in increased liver pathology in WT mice and overwhelming wasting disease in IL-17RA KO mice. Adoptively transferred neutrophils were unable to migrate to tissues and to restore resistant phenotype in infected IL-17RA KO mice but migrated to spleen and liver of infected WT mice and downregulated IFN-γ production and increased survival in an IL-10 dependent manner. Our results underscore the role of IL-17RA in the modulation of IFN-γ-mediated inflammatory responses during infections and uncover a previously unrecognized regulatory mechanism that involves the IL-17RA-mediated recruitment of suppressive IL-10-producing neutrophils

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

La renovación de la palabra en el bicentenario de la Argentina : los colores de la mirada lingüística

El libro reúne trabajos en los que se exponen resultados de investigaciones presentadas por investigadores de Argentina, Chile, Brasil, España, Italia y Alemania en el XII Congreso de la Sociedad Argentina de Lingüística (SAL), Bicentenario: la renovación de la palabra, realizado en Mendoza, Argentina, entre el 6 y el 9 de abril de 2010. Las temáticas abordadas en los 167 capítulos muestran las grandes líneas de investigación que se desarrollan fundamentalmente en nuestro país, pero también en los otros países mencionados arriba, y señalan además las áreas que recién se inician, con poca tradición en nuestro país y que deberían fomentarse. Los trabajos aquí publicados se enmarcan dentro de las siguientes disciplinas y/o campos de investigación: Fonología, Sintaxis, Semántica y Pragmática, Lingüística Cognitiva, Análisis del Discurso, Psicolingüística, Adquisición de la Lengua, Sociolingüística y Dialectología, Didáctica de la lengua, Lingüística Aplicada, Lingüística Computacional, Historia de la Lengua y la Lingüística, Lenguas Aborígenes, Filosofía del Lenguaje, Lexicología y Terminología

Reduced neutrophil chemoattractant production and neutrophil recruitment in the spleen and liver of <i>T. cruzi</i> infected IL-17RA KO mice.

<p>A) Cell numbers in spleen, lymph nodes and liver of WT and IL-17RA KO mice determined at different times after <i>T. cruzi</i> infection. Data are shown as mean ± SD, n = 5 mice per group. P values calculated using two-way ANOVA followed by Bonferroni's posttest. B) Percentage of CD11b+ Gr-1+ neutrophils in spleen and liver of 20-day <i>T. cruzi</i> infected WT and IL-17RA KO mice. Plots are representative one out of five mice. C) Absolute numbers of CD11b+ Gr-1+ neutrophils in spleen (left) and liver (right) of 20-day <i>T. cruzi</i> infected WT and IL-17RA KO mice. Each symbol represents a different mouse and horizontal line indicates the mean. P values calculated with two-tailed T test. D) Concentration of CXCL1, CXCL2 and CXCL10 in spleen and liver homogenates obtained from WT and IL-17RA KO mice at different times post <i>T. cruzi</i> infection. Data are shown as mean ± SD of biological triplicates, normalized to total protein concentration, n = 5 mice per group. P values calculated with two-way ANOVA followed by Bonferroni's posttest. (* p: spleen WT vs spleen KO; # p: liver WT vs liver KO). E) Absolute number or frequency of transferred WT and IL-17RA KO neutrophils detected in bone marrow, blood, spleen and liver of non-infected (NI) and infected (I) WT and IL-17RA KO mice 3 h after i.v. injection. Data are shown as mean ± SD, n = 5 per group. P values calculated with two-tailed T test. Data in A–C and D–E are representative of four and two independent experiments, respectively.</p

IL-10-dependent modulation of IFN-γ production by adoptively transferred neutrophils during <i>T. cruzi</i> infection.

<p>A) Parasitemia determined at day 20 post-infection in infected WT and IL-17RA KO mice adoptively transferred with WT neutrophils. Data are shown as mean ± SD, n = 6 per group. P values calculated with two-tailed T test. B) Concentration of IFN-γ in plasma of 20-day <i>T. cruzi</i> infected WT and IL-17R KO mice adoptively transferred with WT neutrophils. Data are shown as mean ± SD, n = 6 per group. P values calculated with two-tailed T test. C) Survival of <i>T. cruzi</i> infected WT and IL-17R KO mice adoptively transferred with WT neutrophils. P value calculated with a Gehan-Breslow-Wilcoxon test, n = 12 per group. D) Parasitemia determined at day 20 postinfection in infected WT mice adoptively transferred with WT and IL-10 KO neutrophils. Data are shown as mean ± SD, n = 12 per group. P values calculated with two-tailed T test. E) Concentration of IFN-γ in plasma of 20-day <i>T. cruzi</i> infected WT mice adoptively transferred with WT and IL-10 KO neutrophils. Data are shown as mean ± SD, n = 12 per group. P values calculated with two-tailed T test. F) Survival of <i>T. cruzi</i> infected WT mice adoptively transferred with WT and IL-10 KO neutrophils. P value calculated with a Gehan-Breslow-Wilcoxon test, n = 12 per group. Data in A–F are representative of two independent experiments.</p

Hepatic lesions in anti-IFN-γ treated <i>T. cruzi</i> infected WT and IL-17RA KO mice at day 20 post-infection.

a<p>Scale: +: mild; ++:moderate; +++: severe; ++++: extremely severe.</p>b<p>PMN: Polymorphonuclear cells; Mo/Ly: monocyte/lymphocytes.</p