Examinando por Autor "Silva, Pedro H."

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    Human metapneumovirus respiratory infection affects both innate and adaptive intestinal immunity
    (Frontiers Media SA, 2024) Sepúlveda-Alfaro, Javiera; Catalán, Eduardo A.; Vallejos, Omar P.; Ramos-Tapia, Ignacio; Madrid-Muñoz, Cristóbal; Mendoza-León, María J.; Suazo, Isidora D.; Rivera-Asin, Elizabeth; Silva, Pedro H.; Alvarez-Mardones, Oscar; Castillo-Godoy, Daniela P.; Riedel, Claudia A.; Schinnerling, Katina; Ugalde, Juan A.; Soto, Jorge A.; Bueno, Susan M.; Kalergis, Alexis M.; Melo-Gonzalez, Felipe
    Introduction: Respiratory infections are one of the leading causes of morbidity and mortality worldwide, mainly in children, immunocompromised people, and the elderly. Several respiratory viruses can induce intestinal inflammation and alterations in intestinal microbiota composition. Human metapneumovirus (HMPV) is one of the major respiratory viruses contributing to infant mortality in children under 5 years of age worldwide, and the effect of this infection at the gut level has not been studied. Methods: Here, we evaluated the distal effects of HMPV infection on intestinal microbiota and inflammation in a murine model, analyzing several post-infection times (days 1, 3, and 5). Six to eight-week-old C57BL/6 mice were infected intranasally with HMPV, and mice inoculated with a non-infectious supernatant (Mock) were used as a control group. Results: We did not detect HMPV viral load in the intestine, but we observed significant changes in the transcription of IFN-γ in the colon, analyzed by qPCR, at day 1 post-infection as compared to the control group. Furthermore, we analyzed the frequencies of different innate and adaptive immune cells in the colonic lamina propria, using flow cytometry. The frequency of monocyte populations was altered in the colon of HMPV -infected mice at days 1 and 3, with no significant difference from control mice at day 5 post-infection. Moreover, colonic CD8+ T cells and memory precursor effector CD8+ T cells were significantly increased in HMPV-infected mice at day 5, suggesting that HMPV may also alter intestinal adaptive immunity. Additionally, we did not find alterations in antimicrobial peptide expression, the frequency of colonic IgA+ plasma cells, and levels of fecal IgA. Some minor alterations in the fecal microbiota composition of HMPV -infected mice were detected using 16s rRNA sequencing. However, no significant differences were found in β-diversity and relative abundance at the genus level. Discussion: To our knowledge, this is the first report describing the alterations in intestinal immunity following respiratory infection with HMPV infection. These effects do not seem to be mediated by direct viral infection in the intestinal tract. Our results indicate that HMPV can affect colonic innate and adaptive immunity but does not significantly alter the microbiota composition, and further research is required to understand the mechanisms inducing these distal effects in the intestine.
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    Inactivated Vaccine-Induced SARS-CoV-2 Variant-Specific Immunity in Children
    (American Society for Microbiology, 2022-12) Soto, Jorge A.; Melo González, Felipe; Gutierrez Vera, Cristián; Schultz, Bárbara M.; Berríos Rojas, Roslye V.; Rivera Pérez, Daniela; Piña Iturbe, Alejandro; Hoppe Elsholz, Guillermo; Duarte, Luisa F.; Vázquez, Yaneisi; Moreno Tapia, Daniela; Ríos, Mariana; Palacios, Pablo A.; Garcia Betancourt, Richard; Santibañez, Álvaro; Pacheco, Gaspar A.; Mendez, Constanza; Andrade, Catalina A.; Silva, Pedro H.; Diethelm Varela, Benjamín; Astudillo, Patricio; Calvo, Mario; Cárdenas, Antonio; González, Marcela; Goldsack, Macarena; Gutiérrez, Valentina; Potin, Marcela; Schilling, Andrea; Tapia, Lorena I.; Twele, Loreto; Villena, Rodolfo; Grifoni, Albar; Sette, Alessandro; Weiskopf, Daniela; Fasce, Rodrigo A.; Fernández, Jorge; Mora, Judith; Ramírez, Eugenio; Gaete Argel, Aracelly; Acevedo, Mónica L.; Valiente Echeverría, Fernando; Soto Rifo, Ricardo; Retamal Díaz, Angello; Muñoz Jofré, Nathalia; Meng, Xing; Xin, Qianqian; Alarcón Bustamante, Eduardo; González Aramundiz, José V.; Le Corre, Nicole; Álvarez Figueroa, María Javiera; González, Pablo A.; Abarca, Katia; Perret, Cecilia; Carreño, Leandro J.; Bueno, Susan M.; Kalergis, Alexis M.
    Multiple vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been evaluated in clinical trials. However, trials addressing the immune response in the pediatric population are scarce. The inactivated vaccine CoronaVac has been shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. Here, we report interim safety and immunogenicity results of a phase 3 clinical trial for CoronaVac in healthy children and adolescents in Chile. Participants 3 to 17 years old received two doses of CoronaVac in a 4-week interval until 31 December 2021. Local and systemic adverse reactions were registered for volunteers who received one or two doses of CoronaVac. Whole-blood samples were collected from a subgroup of 148 participants for humoral and cellular immunity analyses. The main adverse reaction reported after the first and second doses was pain at the injection site. Four weeks after the second dose, an increase in neutralizing antibody titer was observed in subjects relative to their baseline visit. Similar results were found for activation of specific CD41 T cells. Neutralizing antibodies were identified against the Delta and Omicron variants. However, these titers were lower than those for the D614G strain. Importantly, comparable CD41 T cell responses were detected against these variants of concern. Therefore, CoronaVac is safe and immunogenic in subjects 3 to 17 years old, inducing neutralizing antibody secretion and activating CD41 T cells against SARS-CoV-2 and its variants. (This study has been registered at ClinicalTrials .gov under no. NCT04992260.) IMPORTANCE This work evaluated the immune response induced by two doses of CoronaVac separated by 4 weeks in healthy children and adolescents in Chile. To date, few studies have described the effects of CoronaVac in the pediatric population. Therefore, it is essential to generate knowledge regarding the protection of vaccines in this population. Along these lines, we reported the anti-S humoral response and cellular immune response to several SARS-CoV-2 proteins that have been published and recently studied. Here, we show that a vaccination schedule consisting of two doses separated by 4 weeks induces the secretion of neutralizing antibodies against SARS-CoV-2. Furthermore, CoronaVac induces the activation of CD41 T cells upon stimulation with peptides from the proteome of SARS-CoV-2. These results indicate that, even though the neutralizing antibody response induced by vaccination decreases against the Delta and Omicron variants, the cellular response against these variants is comparable to the response against the ancestral strain D614G, even being significantly higher against Omicron. Copyright © 2022 Soto et al.