Browsing by Author "Rivera-Perez, 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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    A Recombinant BCG Vaccine Is Safe and Immunogenic in Neonatal Calves and Reduces the Clinical Disease Caused by the Respiratory Syncytial Virus
    (2021) Diaz, Fabian E.; Guerra-Maupome, Mariana; McDonald, Paiton O.; Rivera-Perez, Daniela; Kalergis, Alexis M.; McGill, Jodi L.
    The human respiratory syncytial virus (hRSV) constitutes a major health burden, causing millions of hospitalizations in children under five years old worldwide due to acute lower respiratory tract infections. Despite decades of research, licensed vaccines to prevent hRSV are not available. Development of vaccines against hRSV targeting young infants requires ruling out potential vaccine-enhanced disease presentations. To achieve this goal, vaccine testing in proper animal models is essential. A recombinant BCG vaccine that expresses the Nucleoprotein of hRSV (rBCG-N-hRSV) protects mice against hRSV infection, eliciting humoral and cellular immune protection. Further, this vaccine was shown to be safe and immunogenic in human adult volunteers. Here, we evaluated the safety, immunogenicity, and protective efficacy of the rBCG-N-hRSV vaccine in a neonatal bovine RSV calf infection model. Newborn, colostrum-replete Holstein calves were either vaccinated with rBCG-N-hRSV, WT-BCG, or left unvaccinated, and then inoculated via aerosol challenge with bRSV strain 375. Vaccination with rBCG-N-hRSV was safe and well-tolerated, with no systemic adverse effects. There was no evidence of vaccine-enhanced disease following bRSV challenge of rBCG-N-hRSV vaccinated animals, suggesting that the vaccine is safe for use in neonates. Vaccination increased virus-specific IgA and virus-neutralization activity in nasal fluid and increased the proliferation of virus- and BCG-specific CD4+ and CD8+ T cells in PBMCs and lymph nodes at 7dpi. Furthermore, rBCG-N-hRSV vaccinated calves developed reduced clinical disease as compared to unvaccinated control calves, although neither pathology nor viral burden were significantly reduced in the lungs. These results suggest that the rBCG-N-hRSV vaccine is safe in neonatal calves and induces protective humoral and cellular immunity against this respiratory virus. These data from a newborn animal model provide further support to the notion that this vaccine approach could be considered as a candidate for infant immunization against RSV.
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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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    Female offspring gestated in hypothyroxinemia and infected with human Metapneumovirus (hMPV) suffer a more severe infection and have a higher number of activated CD8+ T lymphocytes
    (2022) Funes, Samanta C.; Rios, Mariana; Fernandez-Fierro, Ayleen; Rivera-Perez, Daniela; Soto, Jorge A.; Valbuena, Jose R.; Altamirano-Lagos, Maria J.; Gomez-Santander, Felipe; Jara, Evelyn L.; Zoroquiain, Pablo; Roa, Juan C.; Kalergis, Alexis M.; Riedel, Claudia A.
    Maternal thyroid hormones (THs) are essential for the appropriate development of the fetus and especially for the brain. Recently, some studies have shown that THs deficiency can also alter the immune system development of the progeny and their ability to mount an appropriate response against infectious agents. In this study, we evaluated whether adult mice gestated under hypothyroxinemia (Hpx) showed an altered immune response against infection with human metapneumovirus (hMPV). We observed that female mice gestated under Hpx showed higher clinical scores after seven days of hMPV infection. Besides, males gestated under Hpx have higher lung viral loads at day seven post-infection. Furthermore, the female offspring gestated in Hpx have already reduced the viral load at day seven and accordingly showed an increased proportion of activated (CD71(+) and FasL(+)) CD8(+) T cells in the lungs, which correlated with a trend for a higher histopathological clinical score. These results support that T-4 deficiency during gestation might condition the offspring differently in males and females, enhancing their ability to respond to hMPV.