Examinando por Autor "Alexis M. Kalergis"

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    Characterization of LDLR rs5925 and PCSK9 rs505151 genetic variants frequencies in healthy subjects from northern Chile: Influence on plasma lipid levels
    (2019) Claudio Rojas; Hugo Ramírez; Luis A. Salazar; Alexis M. Kalergis; Anita S. Gálvez; Jorge Escobar‐Vera
    Background: Identification and characterization of genetic variants and their effects on human health may allow to establish relationships between genetic background and susceptibility to developing cardiovascular diseases. LDLR and PCSK9 polymorphisms have been associated with higher lipid levels and risk of cardiovascular diseases. Thus, the main aim of this study was to evaluate genotype distribution and relative allelic frequency of LDLR rs5925 (1959C > T) and PCSK9 rs505151 (23968 A > G) genetic variants and their effects on lipid levels of healthy subjects from northern Chile. Methods: A total of 178 healthy individuals were recruited for this study. The genotyping of rs5925 (LDLR) and rs505151 (PCSK9) polymorphisms was performed by PCR‐RFLP and qPCR, respectively. In addition, glucose and lipid levels were determined and associated with the genetic data. Results: Genotype distribution for LDLR rs5925 polymorphism was as follows: CC = 19%; CT = 53%; and TT = 28% (HWE: χ2 = 0.80; P = .37), and for PCSK9 rs505151 genetic variant was as follows: AA = 93%; AG = 7%; and GG = 0% (HWE: χ2 = 0.22; P = .64). The frequency of T (rs5925) and G (rs505151) mutated alleles was 0.55 and 0.03, respectively. Data showed that individuals carrying LDLR mutated allele (T) presented lower values of total cholesterol, triglycerides, and LDL‐cholesterol when compared to CC homozygous genotype (P < .05). Subgroup analysis revealed that women carrying the PCSK9 mutated allele (G) exhibited higher values of total cholesterol, triglycerides, HDL‐C, and LDL‐C when compared to male group carrying the same genotype (P<05). Conclusions: The effect of LDLR rs5925 and PCSK9 rs505151 gene polymorphisms on lipid levels is associated with gender among healthy subjects from northern Chile.
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    Contribution of Fcy Receptor-Mediated Immunity to the Pathogenesis Caused by the Human Respiratory Syncytial Virus
    (2019) Orlando A. Acevedo; Fabián E. Díaz; Tomas E. Beals; Felipe M. Benavente; Jorge A. Soto Pablo A. González Alexis M. Kalergis; Jorge Escobar Vera; Pablo A. González; Alexis M. Kalergis
    The human Respiratory Syncytial Virus (hRSV) is the leading cause of severe acute lower respiratory tract infections (ALRTIs) in humans at all ages and is the main cause of hospitalization due to pneumonia, asthma, and bronchiolitis in infants. hRSV symptoms mainly develop due to an excessive host immune and inflammatory response in the respiratory tissue. hRSV infection during life is frequent and likely because of non-optimal immunological memory is developed against this virus. Vaccine development against this pathogen has been delayed after the detrimental effects produced in children by vaccination with a formalin-inactivated hRSV preparation (FI-hRSV), which caused enhanced disease upon natural viral infection. Since then, several studies have focused on understanding the mechanisms underlying such disease exacerbation. Along these lines, several studies have suggested that antibodies elicited by immunization with FI-hRSV show low neutralizing capacity and promote the formation of immune complexes containing hRSV (hRSV-ICs), which contribute to hRSV pathogenesis through the engagement of Fc gamma receptors (FcγRs) expressed on the surface of immune cells. Furthermore, a role for FcγRs is supported by studies evaluating the contribution of these molecules to hRSV-induced disease. These studies have shown that FcγRs can modulate viral clearance by the host and the inflammatory response triggered by hRSV infection. In addition, ICs can facilitate viral entry into host cells expressing FcγRs, thus extending hRSV infectivity. In this article, we discuss current knowledge relative to the contribution of hRSV-ICs and FcγRs to the pathogenesis caused by hRSV and their putative role in the exacerbation of the disease caused by this virus after FI-hRSV vaccination. A better understanding FcγRs involvement in the immune response against hRSV will contribute to the development of new prophylactic or therapeutic tools to promote virus clearance with limited inflammatory damage to the airways
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    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) Nicole Le Corre; Katia Abarca; Patricio Astudillo; Marcela Potin; Sofía López; Macarena Goldsack; Vania Valenzuela; Andrea Schilling; Victoria Gaete; Lilian Rubio; Mario Calvo; Loreto Twele; Marcela González; Daniela Fuentes; Valentina Gutiérrez; Felipe Reyes; Lorena I. Tapia; Rodolfo Villena; Angello Retamal-Díaz; Antonio Cárdenas; Eduardo Alarcón-Bustamante; Xing Meng; Qianqian Xin; José V. González-Aramundiz; María Javiera Álvarez-Figueroa; Pablo A. González; Susan M. Bueno; Jorge A. Soto; Cecilia Perret; Alexis M. Kalergis
    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.
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    Inactivated Vaccine-Induced SARS-CoV-2 Variant-SpecificImmunity in Children
    (2022) Jorge A. Soto; Felipe Melo González; Cristián Gutierrez Vera; Bárbara M. Schultz; Roslye V. Berríos Rojas; Daniela Rivera Pérez; Alejandro Piña Iturbe; Guillermo Hoppe Elsholz; Luisa F. Duarte; Yaneisi Vázquez; Daniela Moreno Tapia; Mariana Ríos; Pablo A. Palacios; Richard Garcia Betancourt; Álvaro Santibañez; Gaspar A. Pacheco; Constanza Mendez; Catalina A. Andrade; Pedro H. Silva; Benjamín Diethelm Varela; Patricia Astudillo; Mario Calvo; Antonio Cárdenas; Marcela González; Macarena Goldsack; Valentina Gutiérrez; Marcela Potin; Andrea Schilling; Lorena I. Tapia; Loreto Twele; Rodolfo Villena; Alba Grifoni; Alessandro Sette; Daniela Weiskopf; Rodrigo A. Fasce; Jorge Fernández; Judith Mora; Eugenio Ramírez; Aracelly Gaete Argel; Mónica L. Acevedo; Fernando Valiente Echeverría; Ricardo Soto Rifo; Angello Retamal Díaz; Nathalia Muñoz Jofré; PedCoronaVac03CL Study Group; Xing Meng; Qianqian Xin; Eduardo Alarcón Bustamante; José V. González Aramundiz; Nicole Le Corre; María Javiera Álvarez Figueroa; Pablo A. González; Katia Abarca; Cecilia Perret; Leandro J. Carreño; Susan M. Bueno; Alexis M. Kalergis
    Multiple vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been evaluated in clinical trials. However, trials addressing the immune response in the pediatric population are scarce. The inactivated vaccine CoronaVac has been shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. Here, we report interim safety and immunogenicity results of a phase 3 clinical trial for CoronaVac in healthy children and adolescents in Chile. Participants 3 to 17 years old received two doses of CoronaVac in a 4-week interval until 31 December 2021. Local and systemic adverse reactions were registered for volunteers who received one or two doses of CoronaVac. Whole-blood samples were collected from a subgroup of 148 participants for humoral and cellular immunity analyses. The main adverse reaction reported after the first and second doses was pain at the injection site. Four weeks after the second dose, an increase in neutralizing antibody titer was observed in subjects relative to their baseline visit. Similar results were found for activation of specific CD41 T cells. Neutralizing antibodies were identified against the Delta and Omicron variants. However, these titers were lower than those for the D614G strain. Importantly, comparable CD41 T cell responses were detected against these variants of concern. Therefore, CoronaVac is safe and immunogenic in subjects 3 to 17 years old, inducing neutralizing antibody secretion and activating CD41 T cells against SARS-CoV-2 and its variants. (This study has been registered at ClinicalTrials .gov under no. NCT04992260.)
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    New insights into the pathogenesis of SARS-CoV-2 during and after the COVID- 19 pandemic
    (2024) Jonatan J. Carvajal; Valeria García Castillo; Shelsy V. Cuellar; Claudia P. Campillay Véliz; Camila Salazar Ardiles; Andrea M. Avellaneda; Christian A. Muñoz; Angello Retamal Díaz; Susan M. Bueno; Pablo A. González; Alexis M. Kalergis; Margarita K. Lay
    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the respiratory distress condition known as COVID-19. This disease broadly affects several physiological systems, including the gastrointestinal, renal, and central nervous (CNS) systems, significantly influencing the patient’s overall quality of life. Additionally, numerous risk factors have been suggested, including gender, body weight, age, metabolic status, renal health, preexisting cardiomyopathies, and inflammatory conditions. Despite advances in understanding the genome and pathophysiological ramifications of COVID-19, its precise origins remain elusive. SARS-CoV-2 interacts with a receptor-binding domain within angiotensin-converting enzyme 2 (ACE2). This receptor is expressed in various organs of different species, including humans, with different abundance. Although COVID-19 has multiorgan manifestations, the main pathologies occur in the lung, including pulmonary fibrosis, respiratory failure, pulmonary embolism, and secondary bacterial pneumonia. In the post- COVID-19 period, different sequelae may occur, which may have various causes, including the direct action of the virus, alteration of the immune response, and metabolic alterations during infection, among others. Recognizing the serious adverse health effects associated with COVID-19, it becomes imperative to comprehensively elucidate and discuss the existing evidence surrounding this viral infection, including those related to the pathophysiological effects of the disease and the subsequent consequences. This review aims to contribute to a comprehensive understanding of the impact of COVID-19 and its long-term effects on human health.
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    Oral infectivity through carnivorism in murine model of Trypanosoma cruzi infection
    (2024) Víctor Torres; Víctor Contreras; Bessy Gutiérrez; Juan San Francisco; Alejandro Catalán; José Luis Vega; Kyung-Mee Moon; Leonard J. Foster; Rafael F. de Almeida; Alexis M. Kalergis; Jorge González
    Introduction: Oral transmission of T. cruzi is probably the most frequent transmission mechanism in wild animals. This observation led to the hypothesis that consuming raw or undercooked meat from animals infected with T. cruzi may be responsible for transmitting the infection. Therefore, the general objective of this study was to investigate host-pathogen interactions between the parasite and gastric mucosa and the role of meat consumption from infected animals in the oral transmission of T. cruzi. Methods: Cell infectivity assays were performed on AGS cells in the presence or absence of mucin, and the roles of pepsin and acidic pH were determined. Moreover, groups of five female Balb/c mice were fed with muscle tissue obtained from mice in the acute phase of infection by the clone H510 C8C3hvir of T. cruzi, and the infection of the fed mice was monitored by a parasitemia curve. Similarly, we assessed the infective capacity of T. cruzi trypomastigotes and amastigotes by infecting groups of five mice Balb/c females, which were infected orally using a nasogastric probe, and the infection was monitored by a parasitemia curve. Finally, different trypomastigote and amastigote inoculums were used to determine their infective capacities. Adhesion assays of T. cruzi proteins to AGS stomach cells were performed, and the adhered proteins were detected by western blotting using monoclonal or polyclonal antibodies and by LC-MS/MS and bioinformatics analysis. Results: Trypomastigote migration in the presence of mucin was reduced by approximately 30%, whereas in the presence of mucin and pepsin at pH 3.5, only a small proportion of parasites were able to migrate (∼6%). Similarly, the ability of TCTs to infect AGS cells in the presence of mucin is reduced by approximately 20%. In all cases, 60–100% of the animals were fed meat from mice infected in the acute phase or infected with trypomastigotes or amastigotes developed high parasitemia, and 80% died around day 40 post-infection. The adhesion assay showed that cruzipain is a molecule of trypomastigotes and amastigotes that binds to AGS cells. LC-MS/MS and bioinformatics analysis, also confirmed that transialidase, cysteine proteinases, and gp63 may be involved in TCTs attachment or invasion of human stomach cells because they can potentially interact with different proteins in the human stomach mucosa. In addition, several human gastric mucins have cysteine protease cleavage sites. Discussion: Then, under our experimental conditions, consuming meat from infected animals in the acute phase allows the T. cruzi infection. Similarly, trypomastigotes and amastigotes could infect mice when administered orally, whereas cysteinyl proteinases and trans-sialidase appear to be relevant molecules in this infective process.