Browsing by Author "Melo González, Felipe Andrés"

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    Characterization of the anti-inflammatory capacity of IL-10-Producing neutrophils in response to streptococcus pneumoniae infection
    (FRONTIERS MEDIA SA, 2021) González Carreño, Liliana Andrea; Melo González, Felipe Andrés; Sebastián Quijada, Valentina Pilar; Vallejos Galvez, Omar Patricio; Noguera Mijares, Loreani Paola; Suazo Galvez, Isidora del Carmen; Schultz Lombardic, Bárbara M.; Manosalva, Andres H.; Peñaloza, Hernán F.; Soto Ramírez, Jorge Andres; Parker, Dane; Riedel, Claudia A.; González Muñoz, Pablo Alberto; Kalergis Parra, Alexis Mikes; Bueno Ramírez, Susan
    Neutrophils are immune cells classically defined as pro-inflammatory effector cells. However, current accumulated evidence indicates that neutrophils have more versatile immune-modulating properties. During acute lung infection with Streptococcus pneumoniae in mice, interleukin-10 (IL-10) production is required to temper an excessive lung injury and to improve survival, yet the cellular source of IL-10 and the immunomodulatory role of neutrophils during S. pneumoniae infection remain unknown. Here we show that neutrophils are the main myeloid cells that produce IL-10 in the lungs during the first 48 h of infection. Importantly, in vitro assays with bone-marrow derived neutrophils confirmed that IL-10 can be induced by these cells by the direct recognition of pneumococcal antigens. In vivo, we identified the recruitment of two neutrophil subpopulations in the lungs following infection, which exhibited clear morphological differences and a distinctive profile of IL-10 production at 48 h post-infection. Furthermore, adoptive transfer of neutrophils from WT mice into IL-10 knockout mice (Il10(-/-) ) fully restored IL-10 production in the lungs and reduced lung histopathology. These results suggest that IL-10 production by neutrophils induced by S. pneumoniae limits lung injury and is important to mediate an effective immune response required for host survival.
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    Differential immune response induced by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial
    (2022) Galvez Arriagada, Nicolás Marcelo Salvador; Pacheco Ruidiaz, Gaspar Andrés; Schültz Lombardic, Barbara Melinka; Melo González, Felipe Andrés; Soto Ramírez, Jorge Andrés; Duarte Peñaloza, Luisa Fernanda; González Carreño, Liliana Andrea; Rivera Pérez, Daniela Belén; Ríos Raggio, Mariana; Berríos, Roslye V.; Vazquéz Hernandéz, Yaneisi; Moreno Tapia, Daniela Paz; Vallejos Galvez, Omar Patricio; Andrade Parra, Catalina Andrea; Hoppe Elsholz, Guillermo; Iturriaga, Carolina; Urzua, Marcela; Navarrete, María S.; Rojas González, Álvaro Miguel; Fasce Pineda, Rodrigo Andrés; Fernández, Jorge; Mora, Judith; Ramírez, Eugenio; Gaete Argel, Aracelly; Acevedo Blanco, Mónica Andrea; Valiente Echeverría, Fernando; Soto Rifo, Ricardo; Weiskopf, Daniela; Grifoni, Alba; Sette, Alessandro; Zeng, Gang; Meng, Weining; González Aramundiz, José Vicente; Goldblatt, David; Acuna González, Pablo Ernesto; Abarca Villaseca, Katia; Bueno Ramírez, Susan Marcela; Kalergis Parra, Alexis Mikes
    Background: The development of vaccines to control the COVID-19 pandemic progression is a worldwide priority. CoronaVac® is an inactivated SARS-CoV-2 vaccine approved for emergency use with robust efficacy and immunogenicity data reported in trials in China, Brazil, Indonesia, Turkey, and Chile. Methods: This study is a randomized, multicenter, and controlled phase 3 trial in healthy Chilean adults aged ≥18 years. Volunteers received two doses of CoronaVac® separated by two (0-14 schedule) or four weeks (0-28 schedule). 2,302 volunteers were enrolled, 440 were part of the immunogenicity arm, and blood samples were obtained at different times. Samples from a single center are reported. Humoral immune responses were evaluated by measuring the neutralizing capacities of circulating antibodies. Cellular immune responses were assessed by ELISPOT and flow cytometry. Correlation matrixes were performed to evaluate correlations in the data measured. Results: Both schedules exhibited robust neutralizing capacities with the response induced by the 0-28 schedule being better. No differences were found in the concentration of antibodies against the virus and different variants of concern between schedules. Stimulation of PBMCs with MPs induced the secretion of IFN-γ and the expression of activation induced markers for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-γ secretion. Conclusions: Immunization with CoronaVac® in Chilean adults promotes robust cellular and humoral immune responses. The 0-28 schedule induced a stronger humoral immune response than the 0-14 schedule.
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    Immune responses during COVID-19 breakthrough cases in vaccinated children and adolescents
    (Frontiers Media SA, 2024) Rivera Pérez, Daniela; Méndez Vejar, Constanza Soledad; Diethelm Varela, Benjamín Manuel; Melo González, Felipe Andrés; Vázquez Hernández, Yaneisi; Meng, Xing; Xin, Qianqian; Fasce, Rodrigo A.; Fernández, Jorge; Mora, Judith; Ramírez, Eugenio; Acevedo, Mónica L.; Valiente Echeverria, Fernando; Soto Rifo, Ricardo; Grifoni, Alba; Weiskopf, Daniela; Sette, Alessandro; Astudillo Paredes, Patricio Andrés; Le Corre Pérez, Monique Nicole; Abarca Villaseca, Katia; Perret Pérez, Cecilia; González Muñoz, Pablo Alberto; Soto Ramírez, Jorge Andrés; Bueno Ramírez, Susan; Kalergis, Alexis M.
    Background: Vaccine effectiveness against SARS-CoV-2 infection has been somewhat limited due to the widespread dissemination of the Omicron variant, its subvariants, and the immune response dynamics of the naturally infected with the virus. Methods: Twelve subjects between 3-17 years old (yo), vaccinated with two doses of CoronaVac®, were followed and diagnosed as breakthrough cases starting 14 days after receiving the second dose. Total IgGs against different SARS-CoV-2 proteins and the neutralizing capacity of these antibodies after infection were measured in plasma. The activation of CD4+ and CD8+ T cells was evaluated in peripheral blood mononuclear cells stimulated with peptides derived from the proteins from the wild-type (WT) virus and Omicron subvariants by flow cytometry, as well as different cytokines secretion by a Multiplex assay. Results: 2 to 8 weeks post-infection, compared to 4 weeks after 2nd dose of vaccine, there was a 146.5-fold increase in neutralizing antibody titers against Omicron and a 38.7-fold increase against WT SARS-CoV-2. Subjects showed an increase in total IgG levels against the S1, N, M, and NSP8 proteins of the WT virus. Activated CD4+ T cells showed a significant increase in response to the BA.2 subvariant (p<0.001). Finally, the secretion of IL-2 and IFN-γ cytokines showed a discreet decrease trend after infection in some subjects. Conclusion: SARS-CoV-2 infection in the pediatric population vaccinated with an inactivated SARS-CoV-2 vaccine produced an increase in neutralizing antibodies against Omicron and increased specific IgG antibodies for different SARS-CoV-2 proteins. CD4+ T cell activation was also increased, suggesting a conserved cellular response against the Omicron subvariants, whereas Th1-type cytokine secretion tended to decrease. Clinical Trial Registration: clinicaltrials.gov #NCT04992260