Browsing by Author "Fernández, Jorge"
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- ItemDifferential 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 MikesBackground: 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.
- ItemEffectiveness and duration of a second COVID-19 vaccine booster(2022) Jara, Alejandro; Cuadrado, Cristobal; Undurraga Fourcade, Eduardo Andrés; García, Christian; Najera, Manuel; Bertoglia, María Paz; Vergara, Verónica; Fernández, Jorge; García, Heriberto; Araos, RafaelUsing a prospective national cohort of 3.75 million individuals aged 20 or older, we evaluated the effectiveness against COVID-19 related ICU admissions and death of mRNA-based second vaccine boosters for four different three-dose background regimes: BNT162b2 primary series plus a homologous booster, and CoronaVac primary series plus an mRNA booster, a homologous booster, and a ChAdOx-1 booster. We estimated the vaccine effectiveness weekly from February 14 to August 15, 2022, by estimating hazard ratios of immunization over non-vaccination, accounting for relevant confounders. The overall adjusted effectiveness of a second mRNA booster shot was 88.2% (95%CI, 86.2-89.9) and 90.5% (95%CI 89.4-91.4) against ICU admissions and death, respectively. Vaccine effectiveness showed a mild decrease for all regimens and outcomes, probably associated with the introduction of BA.4 and BA.5 Omicron sub-lineages and immunity waning. The duration of effectiveness suggests that no additional boosters are needed six months following a second booster shot.
- ItemEffectiveness of the second COVID-19 booster against Omicron: a large-scale cohort study in Chile(2023) Jara Vallejos, Alejandro Antonio; Cuadrado, Cristóbal; Undurraga Fourcade, Eduardo Andrés; García, Christian; Nájera, Manuel; Bertoglia, María Paz; Vergara, Verónica; Fernández, Jorge; García-Escorza, Heriberto; Araos, RafaelIn light of the ongoing COVID-19 pandemic and the emergence of new SARSCoV-2 variants, understanding the effectiveness of various booster vaccination regimens is pivotal. In Chile, using a prospective national cohort of 3.75 million individuals aged 20 or older, we evaluate the effectiveness against COVID-19- related intensive care unit (ICU) admissions and death of mRNA based second vaccine boosters for four different three-dose background regimes: BNT162b2 primary series followed by a homologous booster, and CoronaVac primary series followed by an mRNA booster, a homologous booster, and a ChAdOx-1 booster. We estimate the vaccine effectiveness weekly from February 14 to August 15, 2022, by determining hazard ratios of immunization over nonvaccination, accounting for relevant confounders. The overall adjusted effectiveness of a second mRNA booster shot is 88.2% (95%CI, 86.2–89.9) against ICU admissions and 90.5% (95%CI 89.4–91.4) against death. Vaccine effectiveness shows a mild decrease for all regimens and outcomes,probably linked to the introduction of BA.4 and BA.5 Omicron sub-lineages and the waning ofimmunity. Based on our findings, individuals might not need additional boosters for at least 6 months after receiving a second mRNA booster shot in this setting.
- ItemImmune 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
- ItemInsights into neutralizing antibody responses in individuals exposed to SARS-CoV-2 in Chile(2021) Beltrán Pavez, Carolina; Riquelme Barrios, Sebastián; Oyarzún Arrau, Aarón; Gaete Argel, Aracelly; González Stegmaier, Roxana; Cereceda Solis, Karina; Aguirre, Adam; Travisany, Dante; Palma Vejares, Ricardo; Barriga, Gonzalo P.; Gaggero, Aldo; Martínez Valdebenito, Constanza; Le Corre Pérez, Monique Nicole; Ferrés, Marcela; Balcells Marty, María Elvira; Fernández, Jorge; Ramírez, Eugenio; Villarroel, Franz; Valiente Echeverría, Fernando; Soto Rifo, RicardoChile has one of the worst numbers worldwide in terms of SARS-CoV-2 positive cases and COVID-19-related deaths per million inhabitants; thus, characterization of neutralizing antibody (NAb) responses in the general population is critical to understanding of immunity at the local level. Given our inability to perform massive classical neutralization assays due to the scarce availability of BSL-3 facilities in the country, we developed and fully characterized an HIV-based SARS-CoV-2 pseudotype, which was used in a 96-well plate format to investigate NAb responses in samples from individuals exposed to SARS-CoV-2 or treated with convalescent plasma. We also identified samples with decreased or enhanced neutralization activity against the D614G spike variant compared with the wild type, indicating the relevance of this variant in host immunity. The data presented here represent the first insights into NAb responses in individuals from Chile, serving as a guide for future studies in the country.