Browsing by Author "Hoppe-Elsholz, Guillermo"

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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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    SEN1990 is a predicted winged helix-turn-helix protein involved in the pathogenicity of Salmonella enterica serovar Enteritidis and the expression of the gene oafB in the SPI-17
    (2023) Hoppe-Elsholz, Guillermo; Pina-Iturbe, Alejandro; Vallejos, Omar P.; Suazo, Isidora D.; Sepulveda-Alfaro, Javiera; Pereira-Sanchez, Patricia; Martinez-Balboa, Yohana; Catalan, Eduardo A.; Reyes, Pablo; Scaff, Valentina; Bassi, Franco; Campos-Gajardo, Sofia; Aviles, Andrea; Santiviago, Carlos A.; Kalergis, Alexis M.; Bueno, Susan M.
    Excisable genomic islands (EGIs) are horizontally acquired genetic elements that harbor an array of genes with diverse functions. ROD21 is an EGI found integrated in the chromosome of Salmonella enterica serovar Enteritidis (Salmonella ser. Enteritidis). While this island is known to be involved in the capacity of Salmonella ser. Enteritidis to cross the epithelial barrier and colonize sterile organs, the role of most ROD21 genes remains unknown, and thus, the identification of their function is fundamental to understanding the impact of this EGI on bacterium pathogenicity. Therefore, in this study, we used a bioinformatical approach to evaluate the function of ROD21-encoded genes and delve into the characterization of SEN1990, a gene encoding a putative DNA-binding protein. We characterized the predicted structure of SEN1990, finding that this protein contains a three-stranded winged helix-turn-helix (wHTH) DNA-binding domain. Additionally, we identified homologs of SEN1990 among other members of the EARL EGIs. Furthermore, we deleted SEN1990 in Salmonella ser. Enteritidis, finding no differences in the replication or maintenance of the excised ROD21, contrary to what the previous Refseq annotation of the protein suggests. High-throughput RNA sequencing was carried out to evaluate the effect of the absence of SEN1990 on the bacterium's global transcription. We found a downregulated expression of oafB, an SPI-17-encoded acetyltransferase involved in O-antigen modification, which was restored when the deletion mutant was complemented ectopically. Additionally, we found that strains lacking SEN1990 had a reduced capacity to colonize sterile organs in mice. Our findings suggest that SEN1990 encodes a wHTH domain-containing protein that modulates the transcription of oafB from the SPI-17, implying a crosstalk between these pathogenicity islands and a possible new role of ROD21 in the pathogenesis of Salmonella ser. Enteritidis.
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    Subinhibitory antibiotic concentrations promote the excision of a genomic island carried by the globally spread carbapenem- resistant Klebsiella pneumoniae sequence type 258
    (2023) Pina-Iturbe, Alejandro; Hoppe-Elsholz, Guillermo; Suazo, Isidora D.; Kalergis, Alexis M.; Bueno, Susan M.
    The ICEKp258.2 genomic island (GI) has been proposed as an important factor for the emergence and success of the globally spread carbapenem-resistant Klebsiella pneumoniae sequence type (ST) 258. However, a characterization of this horizontally acquired element is lacking. Using bioinformatic and experimental approaches, we found that ICEKp258.2 is not confined to ST258 and ST512, but also carried by ST3795 strains and emergent invasive multidrug-resistant pathogens from ST1519. We also identified several ICEKp258.2- like GIs spread among different K. pneumoniae STs, other Klebsiella species and even other pathogen genera, uncovering horizontal gene transfer events between different STs and bacterial genera. Also, the compara-tive and phylogenetic analyses of the ICEKp258.2- like GIs revealed that the most closely related ICEKp258.2- like GIs were har-boured by ST11 strains. Importantly, we found that subinhibitory concentrations of antibiotics used in treating K. pneumoniae infections can induce the excision of this GI and modulate its gene expression. Our findings provide the basis for the study of ICEKp258.2 and its role in the success of K. pneumoniae ST258. They also highlight the potential role of antibiotics in the spread of ICEKp258.2- like GIs among bacterial pathogens.