Browsing by Author "Kalergis Parra, Alexis Mikes"

Now showing 1 - 11 of 11
  • No Thumbnail Available
    Item
  • Thumbnail Image
    Item
    Chromosomal excision of a new pathogenicity island modulates Salmonella virulence in vivo
    (BENTHAM SCIENCE PUBL LTD, 2013) Tobar Durán, Hugo Eduardo; Salazar Echegarai, Francisco J.; Nieto Pacheco, Pamela Andrea; Palavecino, Christian E.; Sebastian, Vatenlina P.; Riedel Soria, Claudia; Kalergis Parra, Alexis Mikes; Bueno Ramírez, Susan
    Although the excision of unstable pathogenicity islands is a phenomenon that has been described for several virulent bacteria, whether this process directly affects the capacity of these microorganisms to cause disease in their hosts remains unknown. Salmonella enterica serovar Enteritidis (S. Enteritidis) is an enterobacterium that harbors several unstable pathogenicity islands that can excise from the main bacterial chromosome. Here we have evaluated whether excision of one of these pathogenicity islands, denominated as Region of Difference 21 (ROD21), is required for S. Enteritidis to cause disease in the host. By means of genetic targeting of the integrase encoded by the ROD21 we have generated S. Enteritidis strains unable to excise ROD21. The failure to excise ROD21 significantly reduced the capacity to cause a lethal disease and to colonize the spleen and liver of mice, as compared to wild type S. Enteritidis. On the contrary, S. Enteritidis strains overexpressing an excisionase protein increased the frequency of ROD21 excision and showed an improved capacity to cause lethal disease in mice. Accordingly, strains unable to excise ROD21 showed an altered expression of genes located in this pathogenicity island. Our results suggest that the genetic excision of the pathogenicity island ROD21 in S. Enteritidis modulates the capacity of this bacterium to cause disease in mice due to a change in the expression of virulence genes.
  • No Thumbnail Available
    Item
    Different Safety Pattern of an Inactivated SARS-CoV-2 Vaccine (CoronaVac®) According to Age Group in a Pediatric Population from 3 to 17 Years Old, in an Open-Label Study in Chile
    (2023) Le Corre, Nicole; Abarca Villaseca, Katia; Astudillo, Patricio André; Potin Santander, Marcela Patricia; López, Sofía; Goldsack, Macarena; Valenzuela Guerrero, Vania; Schilling Redlich, Andrea; Gaete, Victoria; Rubio, Lilian; Calvo, Mario; Twele, Loreto; González, Marcela; Fuentes, Daniela; Gutiérrez Muñoz, Valentina José; Reyes Zaldivar, Felipe Tomás; Tapia, Lorena I.; Villena, Rodolfo; Retamal Díaz, Angello; Cárdenas, Antonio; Alarcón Bustamante, Eduardo; Xin, Qianqian; González Aramundiz, José Vicente; Álvarez Figueroa, María Javiera; González Muñoz, Pablo Alberto; Bueno Ramírez, Susan; Soto Ramírez, Jorge Andrés; Perret Pérez, Cecilia; Meng, Xing; Kalergis Parra, Alexis Mikes
    During the COVID-19 pandemic, the importance of vaccinating children against SARS-CoV-2 was rapidly established. This study describes the safety of CoronaVac® in children and adolescents between 3- and 17-years-old in a multicenter study in Chile with two vaccine doses in a 4-week interval. For all participants, immediate adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were registered throughout the study. In the safety subgroup, AEs were recorded 28 days after each dose. COVID-19 surveillance was performed throughout the study. A total of 1139 individuals received the first and 1102 the second dose of CoronaVac®; 835 were in the safety subgroup. The first dose showed the highest number of AEs: up to 22.2% of participants reported any local and 17.1% systemic AE. AEs were more frequent in adolescents after the first dose, were transient, and mainly mild. Pain at the inoculation site was the most frequent AE for all ages. Fever was the most frequent systemic AE for 3–5 years old and headache in 6–17 years old. No SAEs or AESIs related to vaccination occurred. Most of the COVID-19 cases were mild and managed as outpatients. CoronaVac® was safe and well tolerated in children and adolescents, with different safety patterns according to age.
  • No Thumbnail Available
    Item
    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.
  • Thumbnail Image
    Item
    Differential Sars-cov-2 antigen specificity of the humoral response inactivated virus-vaccinated, convalescent, and breakthrough subjects
    (2022) Duarte Peñaloza, Luisa Fernanda; Vázquez Hernández, Yaneisi; Diethelm Varela, Benjamin Manuel; Pávez Carrasco, Valentina Ignacia; Berrios Rojas, Roslye; White, Jessica A.; Kalergis Parra, Alexis Mikes; Bueno Ramírez, Susan Marcela; Gonzalez Munoz, Pablo Alberto
    Analytical methods for the differential determination between natural infection with SARS- CoV-2 vs. immunity elicited by vaccination or infection after immunization (breakthrough cases) represent attractive new research venues in the context of the ongoing COVID-19 pandemic caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). Herein, we set out to compare humoral responses against several SARS-CoV-2 structural and non-structural proteins in infected unvaccinated (convalescent), vaccinated, as well as vaccinated and infected (breakthrough) individuals. Our results indicate that immunization with an inactivated SARS-CoV-2 vaccine (CoronaVac) induces significantly higher levels of IgG antibodies against the membrane (M) protein of SARS-CoV-2 as compared to convalescent subjects both, after the primary vaccination schedule and after a booster dose. Moreover, we found that CoronaVac-immunized individuals, after receiving a third vaccine shot, display equivalent levels of N-specific IgG antibodies as convalescents subjects. Regarding non-structural viral proteins, for the two viral proteins ORF3a and NSP8, IgG antibodies were produced in more than 50% of the convalescent subjects. Finally, a logistic regression model and a receiver operating characteristic (ROC) analysis show that combined detection of M and N proteins may be useful as a biomarker to differentiate breakthrough cases from vaccinated and convalescent individuals that did not receive prior vaccination. Taken together, these results suggest that multiple SARS-CoV-2 antigens may be used as differential biomarkers for distinguishing natural infection from vaccination.
  • Thumbnail Image
    Item
    Interplay between Lipid Metabolism, Lipid Droplets, and DNA Virus Infections
    (MDPI, 2022) Farias, Mónica A.; Diethelm-Varela, Benjamín; Navarro, Areli J.; Kalergis Parra, Alexis Mikes; González, Pablo A.
    Lipid droplets (LDs) are cellular organelles rich in neutral lipids such as triglycerides and cholesterol esters that are coated by a phospholipid monolayer and associated proteins. LDs are known to play important roles in the storage and availability of lipids in the cell and to serve as a source of energy reserve for the cell. However, these structures have also been related to oxidative stress, reticular stress responses, and reduced antigen presentation to T cells. Importantly, LDs are also known to modulate viral infection by participating in virus replication and assembly. Here, we review and discuss the interplay between neutral lipid metabolism and LDs in the replication cycle of different DNA viruses, identifying potentially new molecular targets for the treatment of viral infections.
  • Thumbnail Image
    Item
    Neurotrophin Signaling Impairment by Viral Infections in the Central Nervous System
    (SPRINGER INTERNATIONAL PUBLISHING AG, 2022) Bohmwald Prieto, Karen; Andrade Parra, Catalina Andrea; Mora Rivera, Valentina Paz; Muñoz Flores, José Tomas; Ramírez Inostroza, Robinson Alonso; Rojas Hernández, María Fernanda; Kalergis Parra, Alexis Mikes
    Neurotrophins, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT-3), NT-4, and NT-5, are proteins involved in several important functions of the central nervous system. The activation of the signaling pathways of these neurotrophins, or even by their immature form, pro-neurotrophins, starts with their recognition by cellular receptors, such as tropomyosin receptor kinase (Trk) and 75 kD NT receptors (p75NTR). The Trk receptor is considered to have a high affinity for attachment to specific neurotrophins, while the p75NTR receptor has less affinity for attachment with neurotrophins. The correct functioning of these signaling pathways contributes to proper brain development, neuronal survival, and synaptic plasticity. Unbalanced levels of neurotrophins and pro-neurotrophins have been associated with neurological disorders, illustrating the importance of these molecules in the central nervous system. Furthermore, reports have indicated that viruses can alter the normal levels of neurotrophins by interfering with their signaling pathways. This work discusses the importance of neurotrophins in the central nervous system, their signaling pathways, and how viruses can affect them.
  • Thumbnail Image
    Item
    Reduced Immune Response to Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in a Cohort of Immunocompromised Patients in Chile
    (Oxford University Press for the Infectious Diseases Society of America, 2022) Balcells Marty, María Elvira; Le Corre Pérez, Monique Nicole; Durán Santa Cruz, Josefina Gracia; Ceballos Valdivielso, María Elena Andrea; Vizcaya Altamirano, María Cecilia; Mondaca Contreras, Sebastián Patricio; Dib Marambio, Martin Javier; Rabagliati Borie, Ricardo Miguel; Sarmiento Maldonado, Mauricio; Burgos Cañete, Paula Isabel; Espinoza Sepúlveda, Manuel Antonio; Ferres Garrido, Marcela Viviana; Martínez Valdebenito, Constanza Pamela; Ruiz-Tagle Seguel, Cinthya Grace; Ortiz Koh, Catalina Alejandra; Ross Pérez, Patricio Daniel; Budnik Bitran, Sigall; Solari Gajardo, Sandra; Vizcaya Vergara, María De Los Ángeles; Lembach, Hanns; Berríos Rojas, Roslye; Melo González, Felipe; Rios Raggio, Mariana; Kalergis Parra, Alexis Mikes; Bueno Ramírez, Susan Marcela; Nervi Nattero, Bruno
    Background Inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been widely implemented in low- and middle-income countries. However, immunogenicity in immunocompromised patients has not been established. Herein, we aimed to evaluate immune response to CoronaVac vaccine in these patients. Methods This prospective cohort study included 193 participants with 5 different immunocompromising conditions and 67 controls, receiving 2 doses of CoronaVac 8-12 weeks before enrollment. The study was conducted between May and August 2021, at Red de Salud UC-CHRISTUS, Santiago, Chile. Neutralizing antibody (NAb) positivity, total anti-SARS-CoV-2 immunoglobulin G antibody (TAb) concentrations, and T-cell responses were determined. Results NAb positivity and median neutralizing activity were 83.1% and 51.2% for the control group versus 20.6% and 5.7% (both P < .001) in the solid organ transplant group, 41.5% and 19.2% (both P < .0001) in the autoimmune rheumatic diseases group, 43.3% (P < .001) and 21.4% (PP = .001) in the cancer with solid tumors group, 45.5% and 28.7% (both P < .001) in the human immunodeficiency virus (HIV) infection group, 64.3% and 56.6% (both differences not significant) in the hematopoietic stem cell transplant group, respectively. TAb seropositivity was also lower for the solid organ transplant (20.6%; P < .0001), rheumatic diseases (61%; P < .001), and HIV groups (70.9%; P = .003), compared with the control group (92.3%). On the other hand, the number of interferon gamma spot-forming T cells specific for SARS-CoV-2 tended to be lower in all immunocompromising conditions but did not differ significantly between groups. Conclusions Diverse immunocompromising conditions markedly reduce the humoral response to CoronaVac vaccine. These findings suggest that a boosting vaccination strategy should be considered in these vulnerable patients.
  • Thumbnail Image
    Item
    Subinhibitory antibiotic concentrations promote the excision of a genomic island carried by the globally spread carbapenem-resistant Klebsiella pneumoniae ST258
    (Cold Spring HarborLab. Press, Publications Dept., 2023) Piña Iturbe, Luis Alejandro; Hoppe Elsholz, Guillermo Andres; Suazo Galvez, Isidora Del Carmen; Kalergis Parra, Alexis Mikes; Bueno Ramírez, Susan
    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, in agreement with the origin of ST258 from ST11, the comparative and phylogenetic analyses of the ICEKp258.2-like GIs suggested that ICEKp258.2 was acquired from an ST11 strain. 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.
  • No Thumbnail Available
    Item
    Tackling cutaneous herpes simplex virus disease with topical immunomodulators—a call to action
    (2025) Duarte, Luisa F.; Carbone Schellman, Javier; Bueno Ramírez, Susan Marcela; Kalergis Parra, Alexis Mikes; Riedel, Claudia A.; González Muñoz, Pablo Alberto
  • Thumbnail Image
    Item
    The impact of the micronutrient iodine in health and diseases
    (Bellwether Publishing, Ltd., 2020) Opazo, María Cecilia; Riedel, Claudia A.; Coronado, Arrazola Irenice; Vallejos Gálvez, Omar Patricio; Kalergis Parra, Alexis Mikes; Bueno Ramírez, Susan Marcela; Moreno Reyes, Rodrigo; Fardella Bello, Carlos Enrique; Mosso Gómez, Lorena Montserrat
    © 2020 Taylor & Francis Group, LLC.Adequate iodine nutrition is crucial for all mammals by playing his starring role as a component of thyroid hormones, which are key regulators of cellular processes for life such as differentiation, growth, function, and metabolism. Deficiency or excess of iodine in the diet are worldwide highly frequent conditions that are responsible of health problems like hypothyroidism, hypothyroxinemia, goiter, thyroiditis, hyperthyroidism, and autoimmune thyroid diseases among others. The incorporation of iodine in salt or other nutrients resolved the consequences of severe iodine deficiency like goiter, cretinism. However, this strategy in several countries led to other ailments like Hashimoto autoimmune thyroiditis, hyperthyroidism, and hypothyroidism. The goal of this review is to analyze and discuss the different aspects of iodine nutrition for human health comprising its biological role through thyroid hormones, pathogen control, and the regulation of the intestinal microbiota.