HORMAZABAL CASTILLO, JUAN PATRICIO
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HORMAZABAL CASTILLO, JUAN PATRICIO
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jhormazabal@udd.cl
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57225278430

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2024 2024 2023 2023 2022 2022 2021 2021 2020 2020 0.0 0.0 1.0 1.0 2.0 2.0 3.0 3.0 4.0 4.0 5.0 5.0 6.0 6.0

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SARS-CoV-2 infectivity and antigenic evasion: spotlight on isolated Omicron sub-lineages

2024 , Aldo Barrera , Constanza Martínez-Valdebenito , Jenniffer Angulo , Carlos Palma , HORMAZABAL CASTILLO, JUAN PATRICIO , VIAL COX, MARIA CECILIA , AGUILERA SANHUEZA, XIMENA PAZ , Pablo Castillo-Torres , Catalina Pardo-Roa , María Elvira Balcells , Bruno Nervi , Nicole Le Corre , Marcela Ferrés

Since the SARS-CoV-2 outbreak in 2019, a diversity of viral genomic variants has emerged and spread globally due to increased transmissibility, pathogenicity, and immune evasion. By the first trimester of 2023 in Chile, as in most countries, BQ and XBB were the predominant circulating sub-lineages of Omicron. The molecular and antigenic characteristics of these variants have been mainly determined using non-authentic spike pseudoviruses, which is often described as a limitation. Additionally, few comparative studies using isolates from recent Omicron sub-lineages have been conducted. In this study, we isolated SARS-CoV-2 variants from clinical samples, including the ancestral B.1.1, Delta, Omicron BA.1, and sub-lineages of BA.2 and BA.5. We assessed their infectivity through cell culture infections and their antibody evasion using neutralization assays. We observed variations in viral plaque size, cell morphology, and cytotoxicity upon infection in Vero E6-TMPRSS2 cells for each variant compared to the ancestral B.1.1 virus. BA.2-derived sub-variants, such as XBB.1.5, showed attenuated viral replication, while BA.5-derived variants, such as BQ.1.1, exhibited replication rates similar to the ancestral SARS-CoV-2 virus. Similar trends were observed in intestinal Caco-2 cells, except for Delta. Antibody neutralization experiments using sera from individuals infected during the first COVID-19 wave (FWI) showed a consistent but moderate reduction in neutralization against Omicron sub-lineages. Interestingly, despite being less prevalent, BQ.1.1 showed a 6.1-fold greater escape from neutralization than XBB.1.5. Neutralization patterns were similar when tested against sera from individuals vaccinated with 3xBNT162b2 (PPP) or Coronavac-Coronavac-BNT162b2 (CCP) schedules. However, CCP sera showed 2.3-fold higher neutralization against XBB.1.5 than FWI and PPP sera. This study provides new insights into the differences between BA.2 and BA.5-derived variants, leading to their eventual outcompetition. Our analysis offers important evidence regarding the balance between infectivity and antigenic escape that drives the evolution of second-generation SARS-CoV-2 variants in the population.

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Chaperone mediated autophagy contributes to the newly synthesized histones H3 and H4 quality control

2022 , HORMAZABAL CASTILLO, JUAN PATRICIO , Francisco Saavedra , Claudia Espinoza-Arratia , Nicolas W Martinez , Tatiana Cruces , Iván E Alfaro , Alejandra Loyola

Abstract Although there are several pathways to ensure that proteins are folded properly in the cell, little is known about the molecular mechanisms regulating histone folding and proteostasis. In this work, we identified that chaperone-mediated autophagy (CMA) is the main pathway involved in the degradation of newly synthesized histones H3 and H4. This degradation is finely regulated by the interplay between HSC70 and tNASP, two histone interacting proteins. tNASP stabilizes histone H3 levels by blocking the direct transport of histone H3 into lysosomes. We further demonstrate that CMA degrades unfolded histone H3. Thus, we reveal that CMA is the main degradation pathway involved in the quality control of histone biogenesis, evidencing an additional mechanism in the intricate network of histone cellular proteostasis.

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Deep immunophenotyping reveals biomarkers of multisystemic inflammatory syndrome in children in a Latin American cohort

2022 , REY JURADO, EMMA , Yazmin Espinosa , Camila Astudillo , CORTES SALINAS, LINA JIMENA , HORMAZABAL CASTILLO, JUAN PATRICIO , Fernanda Cofré , Cecilia Piñera , Loreani P. Noguera , Ricardo González , Alexander Bataszew , MUÑOZ VENTURELLI, PAULA ANDREA , Dona Benadof , Patricia Álvarez , Valeria Acevedo , VIAL CLARO, PABLO AGUSTIN , VIAL COX, MARIA CECILIA , POLI HARLOWE, MARIA CECILIA BERTA

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Immunization and SARS-CoV-2 Antibody Seroprevalence in a Country with High Vaccination Coverage: Lessons from Chile

2022 , AGUILERA SANHUEZA, XIMENA PAZ , Gloria Icaza , GONZALEZ WIEDMAIER, CLAUDIA MARTA , RUBILAR RAMIREZ, PAOLA , APABLAZA SALINAS, MAURICIO IVÁN , Muriel Ramírez-Santana , PEREZ ACUÑA, CLAUDIA VERONICA , CORTES SALINAS, LINA JIMENA , Loreto Núñez-Franz , Rubén Quezada-Gaete , CASTILLO LABORDE, CARLA CECILIA , Juan Correa , Macarena Said , HORMAZABAL CASTILLO, JUAN PATRICIO , VIAL COX, MARIA CECILIA , VIAL CLARO, PABLO AGUSTIN

Chile is among the most successful nations worldwide in terms of its COVID-19 vaccine rollout. By 31 December 2021, 84.1% of the population was fully vaccinated, and 56.1% received booster doses using different COVID-19 vaccines. In this context, we aimed to estimate the prevalence of anti-SARS-CoV-2 antibodies following the infection and vaccination campaign. Using a three-stage stratified sampling, we performed a population-based cross-sectional serosurvey based on a representative sample of three Chilean cities. Selected participants were blood-sampled on-site and answered a short COVID-19 and vaccination history questionnaire using Wantai SARS-CoV-2 Ab ELISA to determine seroprevalence. We recruited 2198 individuals aged 7–93 between 5 October and 25 November 2021; 2132 individuals received COVID-19 vaccinations (97%), 67 (3.1%) received one dose, 2065 (93.9%) received two doses, and 936 received the booster jab (42.6%). Antibody seroprevalence reached 97.3%, ranging from 40.9% among those not vaccinated to 99.8% in those with booster doses (OR = 674.6, 154.8–2938.5). SARS-CoV-2 antibodies were associated with vaccination, previous COVID-19 diagnosis, age group, and city of residence. In contrast, we found no significant differences in the type of vaccine used, education, nationality, or type of health insurance. We found a seroprevalence close to 100%, primarily due to the successful vaccination program, which strongly emphasizes universal access.

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Overcoming Health Inequities: Spatial Analysis of Seroprevalence and Vaccination Against COVID-19 in Chile

2024 , Muriel Ramírez-Santana , Juan Correa , Loreto Núñez Franz , APABLAZA SALINAS, MAURICIO IVÁN , RUBILAR RAMIREZ, PAOLA ANDREA , VIAL COX, MARIA CECILIA , CORTES SALINAS, LINA JIMENA , HORMAZABAL CASTILLO, JUAN PATRICIO , Luis Canales , VIAL CLARO, PABLO AGUSTIN , AGUILERA SANHUEZA, XIMENA PAZ

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Factors influencing neutralizing antibody response to the original SARS-CoV-2 virus and the Omicron variant in a high vaccination coverage country, a population-based study

2023 , HORMAZABAL CASTILLO, JUAN PATRICIO , Loreto Nuñez-Franz , RUBILAR RAMIREZ, PAOLA ANDREA , APABLAZA SALINAS, MAURICIO IVÁN , VIAL COX, MARIA CECILIA , CORTES SALINAS, LINA JIMENA , Macarena Said , Kathya Olivares , VIAL CLARO, PABLO AGUSTIN , Muriel Ramírez-Santana , GONZALEZ WIEDMAIER, CLAUDIA MARTA , Natalia González , AGUILERA SANHUEZA, XIMENA PAZ

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SARS-CoV-2 Neutralizing Antibodies in Chile after a Vaccination Campaign with Five Different Schemes

2022 , AGUILERA SANHUEZA, XIMENA PAZ , HORMAZABAL CASTILLO, JUAN PATRICIO , VIAL COX, MARIA CECILIA , CORTES SALINAS, LINA JIMENA , GONZALEZ WIEDMAIER, CLAUDIA MARTA , RUBILAR RAMIREZ, PAOLA , APABLAZA SALINAS, MAURICIO IVÁN , Muriel Ramírez-Santana , Gloria Icaza , Loreto Nuñez-Franz , Rubén Quezada-Gate , Macarena Said , PEREZ ACUÑA, CLAUDIA VERONICA , CASTILLO LABORDE, CARLA CECILIA , Carolina Sacristán Ramírez , VIAL CLARO, PABLO AGUSTIN

Using levels of neutralizing antibodies (nAbs), we evaluate the successful Chilean SARS-CoV-2 vaccine campaign, which combines different vaccine technologies and heterologous boosters. From a population-based study performed in November 2021, we randomly selected 120 seropositive individuals, organized into six groups of positive samples (20 subjects each) according to natural infection history and the five most frequent vaccination schemes. We conclude that the booster dose, regardless of vaccine technology or natural infection, and mRNA vaccines significantly improve nAbs response.

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A Third Dose of SARS-CoV-2 mRNA Vaccine Improves Immune Response in Chronic Kidney Disease Patients

2023 , POLI HARLOWE, MARIA CECILIA BERTA , VIAL COX, MARIA CECILIA , REY JURADO, EMMA , Natalia González , CORTES SALINAS, LINA JIMENA , HORMAZABAL CASTILLO, JUAN PATRICIO , Carolina Ramírez-Riffo , Javiera de la Cruz , Camilo Ulloa

Chronic kidney disease (CKD) patients have an increased risk of morbidity and mortality following SARS-CoV-2 infection. Vaccination in these patients is prioritized, and monitoring of the immune response is paramount to define further vaccination strategies. This prospective study included a cohort of 100 adult CKD patients: 48 with kidney transplant (KT) and 52 on hemodialysis without prior COVID-19. The patients were assessed for humoral and cellular immune responses after four months of an anti-SARS-CoV-2 primary two-dose vaccination scheme (CoronaVac or BNT162b2) and one month after a booster third dose of BNT162b2 vaccine. We identified poor cellular and humoral immune responses in the CKD patients after a primary vaccination scheme, and these responses were improved by a booster. Robust polyfunctional CD4+ T cell responses were observed in the KT patients after a booster, and this could be attributed to a higher proportion of the patients having been vaccinated with homologous BNT162b2 schemes. However, even after the booster, the KT patients exhibited lower neutralizing antibodies, attributable to specific immunosuppressive treatments. Four patients suffered severe COVID-19 despite three-dose vaccination, and all had low polyfunctional T-cell responses, underscoring the importance of this functional subset in viral protection. In conclusion, a booster dose of SARS-CoV-2 mRNA vaccine in CKD patients improves the impaired humoral and cellular immune responses observed after a primary vaccination scheme.

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Chaperone Mediated Autophagy Degrades TDP-43 Protein and Is Affected by TDP-43 Aggregation

2020 , Fernando Ormeño , HORMAZABAL CASTILLO, JUAN PATRICIO , José Moreno , Felipe Riquelme , Javiera Rios , Alfredo Criollo , Amelina Albornoz , Iván E. Alfaro , Mauricio Budini

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Humoral immune response in people living with HIV after administration of SARS-CoV-2 vaccine CoronaVac or BNT162b2 or CoronaVac/BNT162b2 booster sequence: A cross-sectional study

2024 , Marcelo Wolff , Paulo Charpentier , Andrea Canals , VIAL COX, MARIA CECILIA , HORMAZABAL CASTILLO, JUAN PATRICIO , CORTES SALINAS, LINA JIMENA , Macarena Silva

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