Browsing by Author "Moreno-Tapia, Daniela"

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    A Booster Dose of CoronaVac Increases Neutralizing Antibodies and T Cells that Recognize Delta and Omicron Variants of Concern
    (2022) Schultz, Barbara M.; Melo-Gonzalez, Felipe; Duarte, Luisa F.; Galvez, Nicolas M. S.; Pacheco, Gaspar A.; Soto, Jorge A.; Berrios-Rojas, Roslye, V; Gonzalez, Liliana A.; Moreno-Tapia, Daniela; Rivera-Perez, Daniela; Rios, Mariana; Vazquez, Yaneisi; Hoppe-Elsholz, Guillermo; Andrade-Parra, Catalina A.; Vallejos, Omar P.; Pina-Iturbe, Alejandro; Iturriaga, Carolina; Urzua, Marcela; Navarrete, Maria S.; Rojas, Alvaro; Fasce, Rodrigo; Fernandez, Jorge; Mora, Judith; Ramirez, Eugenio; Gaete-Argel, Aracelly; Acevedo, Monica; Valiente-Echeverria, Fernando; Soto-Rifo, Ricardo; Weiskopf, Daniela; Grifoni, Alba; Sette, Alessandro; Zeng, Gang; Meng, Weining; Gonzalez-Aramundiz, Jose, V; Gonzalez, Pablo A.; Abarca, Katia; Kalergis, Alexis M.; Bueno, Susan M.
    CoronaVac is an inactivated SARS-CoV-2 vaccine approved by the World Health Organization (WHO). Previous studies reported increased levels of neutralizing antibodies and specific T cells 2 and 4 weeks after two doses of CoronaVac; these levels were significantly reduced at 6 to 8 months after the two doses. Here, we report the effect of a booster dose of CoronaVac on the anti-SARS-CoV-2 immune response generated against the variants of concern (VOCs), Delta and Omicron, in adults participating in a phase III clinical trial in Chile. Volunteers immunized with two doses of CoronaVac in a 4-week interval received a booster dose of the same vaccine between 24 and 30 weeks after the second dose. Neutralization capacities and T cell activation against VOCs Delta and Omicron were assessed 4 weeks after the booster dose. We observed a significant increase in neutralizing antibodies 4 weeks after the booster dose. We also observed a rise in anti-SARS-CoV-2-specific CD4(+) T cells over time, and these cells reached a peak 4 weeks after the booster dose. Furthermore, neutralizing antibodies and SARS-CoV-2-specific T cells induced by the booster showed activity against VOCs Delta and Omicron. Our results show that a booster dose of CoronaVac increases adults' humoral and cellular anti-SARS-CoV-2 immune responses. In addition, immunity induced by a booster dose of CoronaVac is active against VOCs, suggesting adequate protection. IMPORTANCE CoronaVac is an inactivated vaccine against SARS-CoV-2 that has been approved by WHO for emergency use. Phase III clinical trials are in progress in several countries, including China, Brazil, Turkey, and Chile, and have shown safety and immunogenicity after two doses of the vaccine. This report characterizes immune responses induced by two doses of CoronaVac followed by a booster dose 5 months after the second dose in healthy Chilean adults. The data reported here show that a booster dose increased the immune responses against SARS-CoV-2, enhancing levels of neutralizing antibodies against the ancestral strain and VOCs. Similarly, anti-SARS-CoV-2 CD4(+) T cell responses were increased following the booster dose. In contrast, levels of gamma interferon secretion and T cell activation against the VOCs Delta and Omicron were not significantly different from those for the ancestral strain. Therefore, a third dose of CoronaVac in a homologous vaccination schedule improves its immunogenicity in healthy volunteers.
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    Differences in the immune response elicited by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial
    (2022) Galvez, Nicolas M. S.; Pacheco, Gaspar A.; Schultz, Barbara M.; Melo-Gonzalez, Felipe; Soto, Jorge A.; Duarte, Luisa F.; Gonzalez, Liliana A.; Rivera-Perez, Daniela; Rios, Mariana; Berrios, Roslye, V; Vazquez, Yaneisi; Moreno-Tapia, Daniela; Vallejos, Omar P.; Andrade, Catalina A.; Hoppe-Elsholz, Guillermo; Iturriaga, Carolina; Urzua, Marcela; Navarrete, Maria S.; Rojas, Alvaro; Fasce, Rodrigo; Fernandez, Jorge; Mora, Judith; Ramirez, Eugenio; Gaete-Argel, Aracelly; Acevedo, Monica L.; Valiente-Echeverria, Fernando; Soto-Rifo, Ricardo; Weiskopf, Daniela; Grifoni, Alba; Sette, Alessandro; Zeng, Gang; Meng, Weining; Gonzalez-Aramundiz, Jose, V; Johnson, Marina; Goldblatt, David; Gonzalez, Pablo A.; Abarca, Katia; Bueno, Susan M.; Kalergis, Alexis M.
    Background: The development of vaccines to control the coronavirus disease 2019 (COVID-19) pandemic progression is a worldwide priority. CoronaVac is an inactivated severe acute respiratory syndrome coronavirus 2 (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 & GE;18 years. Volunteers received two doses of CoronaVac separated by 2 (0-14 schedule) or 4 weeks (0-28 schedule); 2302 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 (VOCs) between schedules. Stimulation of peripheral blood mononuclear cells (PBMCs) with Mega pools of Peptides (MPs) induced the secretion of interferon (IFN)-gamma and the expression of activation induced markers in CD4(+) T cells for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-gamma 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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    Limited Heme Oxygenase Contribution to Modulating the Severity of Salmonella enterica serovar Typhimurium Infection
    (SPRINGER INTERNATIONAL PUBLISHING AG, 2022) Sebastian, Valentina P.; Moreno-Tapia, Daniela; Melo-Gonzalez, Felipe; Hernandez-Caceres, Maria P.; Salazar, Geraldyne A.; Pardo-Roa, Catalina; Farias, Monica A.; Vallejos, Omar P.; Schultz, Barbara M.; Morselli, Eugenia; Alvarez-Lobos, Manuel M.; Gonzalez, Pablo A.; Kalergis, Alexis M.; Bueno, Susan M.
    An important virulence trait of Salmonella enterica serovar Typhimurium (S. Typhimurium) is the ability to avoid the host immune response, generating systemic and persistent infections. Host cells play a crucial role in bacterial clearance by expressing the enzyme heme oxygenase 1 (Hmox1), which catalyzes the degradation of heme groups into Fe2+, biliverdin, and carbon monoxide (CO). The role of Hmox1 activity during S. Typhimurium infection is not clear and previous studies have shown contradictory results. We evaluated the effect of pharmacologic modulation of Hmox1 in a mouse model of acute and persistent S. Typhimurium infection by administering the Hmox1 activity inductor cobalt protoporphyrin-IX (CoPP) or inhibitor tin protoporphyrin-IX (SnPP) before infection. To evaluate the molecular mechanism involved, we measured the colocalization of S. Typhimurium and autophagosome and lysosomal markers in macrophages. Administering CoPP reduced the bacterial burden in organs of mice 5 days post-infection, while SnPP-treated mice showed bacterial loads similar to vehicle-treated mice. Furthermore, CoPP reduced bacterial loads when administered after infection in macrophages in vitro and in a persistent infection model of S. Typhimurium in vivo, while tin protoporphyrin-IX (SnPP) treatment resulted in a bacterial burden similar to vehicle-treated controls. However, we did not observe significant differences in co-localization of green fluorescent protein (GFP)-labeled S. Typhimurium with the autophagic vesicles marker microtubule-associated protein 1A/1B-light chain 3 (LC3) and the lysosomal marker lysosomal-associated membrane protein 1 (LAMP-1) in macrophages treated with CoPP. Our results suggest that CoPP can enhance antimicrobial activity in response to Salmonella infection, reducing bacterial dissemination and persistence in mice, in a CO and autophagy- independent manner.