Browsing by Author "Pardo-Roa, Catalina"
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- ItemEmergence and rapid dissemination of highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b in wild birds, Chile.(SPRINGER INTERNATIONAL PUBLISHING AG, 2023) Ariyama, Naomi; Pardo-Roa, Catalina; Munoz, Gabriela; Aguayo, Carolina; Avila, Claudia; Mathieu, Christian; Brito, Barbara; Medina, Rafael; Johow, Magdalena; Neira, VictorIn December 2022, HPAI H5N1 clade 2.3.4.4b emerged in Chile. We detected the virus in 93 wild bird samples and sequenced the whole genome of nine Chilean strains from pelicans and gulls. Phylogenetic analysis suggests at least two different HPAI viral clusters in South America.
- ItemFirst report and genetic characterization of Seneca Valley virus (SVV) in Chile(SPRINGER INTERNATIONAL PUBLISHING AG, 2022) Bennett, Benjamin; Urzua-Encina, Constanza; Pardo-Roa, Catalina; Ariyama, Naomi; Lecocq, Claudio; Rivera, Carlos; Badia, Catalina; Suarez, Paulina; Agredo, Michel; Aguayo, Carolina; Avila, Claudia; Araya, Hugo; Perez, Patricio; Berrios, Felipe; Aguero, Belen; Mendieta, Vanessa; Pituco, Edviges Maristela; de Almeida, Iassudara Garcia; Medina, Rafael; Brito, Barbara; Johow, Magdalena; Neira Ramirez, VictorSeneca Valley virus (SVV) is a non-enveloped RNA virus and the only member of the Senecavirus A (SVA) species, in the Senecavirus genus, Picornaviridae family. SVV infection causes vesicular lesions in the oral cavity, snout and hooves of pigs. This infection is clinically indistinguishable from trade-restrictions-related diseases such as foot-and-mouth disease. Other clinical manifestations include diarrhoea, anorexia, lethargy, neurological signs and mortality in piglets during their first week of age. Before this study, Chile was considered free of vesicular diseases of swine, including SVV. In April 2022, a suspected case of vesicular disease in a swine farm was reported in Chile. The SVV was confirmed and other vesicular diseases were ruled out. An epidemiological investigation and phylogenetic analyses were performed to identify the origin and extent of the outbreak. Three hundred ninety-five samples from 44 swine farms were collected, including faeces (208), oral fluid (28), processing fluid (14), fresh semen (61), environmental samples (80) and tissue from lesions (4) for real-time RT-PCR detection. Until June 2022, the SVV has been detected in 16 out of 44 farms, all epidemiologically related to the index farm. The closest phylogenetic relationship of the Chilean SVV strain is with viruses collected from swine in California in 2017. The direct cause of the SVV introduction has not yet been identified; however, the phylogenetic analyses suggest the USA as the most likely source. Since the virus remains active in the environment, transmission by fomites such as contaminated feed cannot be discarded. Further studies are needed to determine the risk of the introduction of novel SVV and other transboundary swine pathogens to Chile.
- ItemHighly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus in Wild Birds, Chile(2023) Ariyama, Naomi; Pardo-Roa, Catalina; Muñoz, Gabriela; Aguayo, Carolina; Ávila, Claudia; Mathieu, Christian; Almonacid Cárdenas, Leonardo Iván; Medina, Rafael; Brito, Barbara; Johow, Magdalena; Neira, VíctorIn December 2022, highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus emerged in Chile. We detected H5N1 virus in 93 samples and obtained 9 whole-genome sequences of strains from wild birds. Phylogenetic analysis suggests multiple viral introductions into South America. Continued surveillance is needed to assess risks to humans and domestic poultry.
- ItemInduction of SARS-CoV-2 neutralizing antibodies by CoronaVac and BNT162b2 vaccines in naive and previously infected individuals(2022) Muena, Nicolas A.; Garcia-Salum, Tamara; Pardo-Roa, Catalina; Jose Avendano, Maria; Serrano, Eileen F.; Levican, Jorge; Almonacid, Leonardo, I; Valenzuela, Gonzalo; Poblete, Estefany; Strohmeier, Shirin; Salinas, Erick; Munoz, Andres; Haslwanter, Denise; Dieterle, Maria Eugenia; Jangra, Rohit K.; Chandran, Kartik; Gonzalez, Claudia; Riquelme, Arnoldo; Krammer, Florian; Tischler, Nicole D.; Medina, Rafael A.Interpretation The decay of nAbs titres in previously infected individuals over time indicates that vaccination is needed to boost humoral memory responses. Immunization of naydve individuals with two doses of CoronaVac induced nAbs titres that were significantly lower to that of convalescent patients, and similar to vaccination with one dose of BTN162b2. The real life effectiveness for CoronaVac in Chile was higher than estimated; indicating that lower titres and additional cellular immune responses induced by CoronaVac might afford protection in a highly immunized population. Nevertheless, the lower nAb titre induced by two doses of CoronaVac as compared to the BTN162b2 vaccine in naydve individuals, highlights the need of booster immunizations over time to maintain protec-tive levels of antibody, particularly with the emergence of new SARS-CoV-2 variants. Funding FONDECYT 1161971, 1212023, 1181799, FONDECYT Postdoctorado 3190706 and 3190648, ANID Becas/ Doctorado Nacional 21212258, PIA ACT 1408, CONICYT REDES180170, Centro Ciencia & Vida, FB210008, Finan-ciamiento Basal para Centros Cient?ficos y Tecnol?ogicos de Excelencia grants from the Agencia Nacional de Inves-tigaci?on y Desarrollo (ANID) of Chile; NIH-NIAD grants U19AI135972, R01AI132633 and contracts HHSN272201400008C and 75N93019C00051; the JPB Foundation, the Open Philanthropy Project grant 2020-215611 (5384); and by anonymous donors. The funders had no role in study design, data collection and analysis, deci-sion to publish, or preparation of the manuscript. Copyright (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
- ItemLimited Heme Oxygenase Contribution to Modulating the Severity of Salmonella enterica serovar Typhimurium Infection(SPRINGER INTERNATIONAL PUBLISHING AG, 2022) Sebastian, Valentina P.; Moreno-Tapia, Daniela; Melo-Gonzalez, Felipe; Hernandez-Caceres, Maria P.; Salazar, Geraldyne A.; Pardo-Roa, Catalina; Farias, Monica A.; Vallejos, Omar P.; Schultz, Barbara M.; Morselli, Eugenia; Alvarez-Lobos, Manuel M.; Gonzalez, Pablo A.; Kalergis, Alexis M.; Bueno, Susan M.An important virulence trait of Salmonella enterica serovar Typhimurium (S. Typhimurium) is the ability to avoid the host immune response, generating systemic and persistent infections. Host cells play a crucial role in bacterial clearance by expressing the enzyme heme oxygenase 1 (Hmox1), which catalyzes the degradation of heme groups into Fe2+, biliverdin, and carbon monoxide (CO). The role of Hmox1 activity during S. Typhimurium infection is not clear and previous studies have shown contradictory results. We evaluated the effect of pharmacologic modulation of Hmox1 in a mouse model of acute and persistent S. Typhimurium infection by administering the Hmox1 activity inductor cobalt protoporphyrin-IX (CoPP) or inhibitor tin protoporphyrin-IX (SnPP) before infection. To evaluate the molecular mechanism involved, we measured the colocalization of S. Typhimurium and autophagosome and lysosomal markers in macrophages. Administering CoPP reduced the bacterial burden in organs of mice 5 days post-infection, while SnPP-treated mice showed bacterial loads similar to vehicle-treated mice. Furthermore, CoPP reduced bacterial loads when administered after infection in macrophages in vitro and in a persistent infection model of S. Typhimurium in vivo, while tin protoporphyrin-IX (SnPP) treatment resulted in a bacterial burden similar to vehicle-treated controls. However, we did not observe significant differences in co-localization of green fluorescent protein (GFP)-labeled S. Typhimurium with the autophagic vesicles marker microtubule-associated protein 1A/1B-light chain 3 (LC3) and the lysosomal marker lysosomal-associated membrane protein 1 (LAMP-1) in macrophages treated with CoPP. Our results suggest that CoPP can enhance antimicrobial activity in response to Salmonella infection, reducing bacterial dissemination and persistence in mice, in a CO and autophagy- independent manner.
- ItemOmicron variant Spike-specific antibody binding and Fc activity are preserved in recipients of mRNA or inactivated COVID-19 vaccines(2022) Bartsch, Yannic C.; Tong, Xin; Kang, Jaewon; Avendano, Maria Jose; Serrano, Eileen F.; Garcia-Salum, Tamara; Pardo-Roa, Catalina; Riquelme, Arnoldo; Cai, Yongfei; Renzi, Isabella; Stewart-Jones, Guillaume; Chen, Bing; Medina, Rafael A.; Alter, GalitThe Omicron variant of SARS-CoV-2 has been shown to evade neutralizing antibodies elicited by vaccination or infection. Despite the global spread of the Omicron variant, even among highly vaccinated populations, death rates have not increased concomitantly. These data suggest that immune mechanisms beyond antibody-mediated virus neutralization may protect against severe disease. In addition to neutralizing pathogens, antibodies contribute to control and clearance of infections through Fc effector mechanisms. Here, we probed the ability of vaccine-induced antibodies to drive Fc effector activity against the Omicron variant using samples from individuals receiving one of three SARS-CoV-2 vaccines. Despite a substantial loss of IgM, IgA, and IgG binding to the Omicron variant receptor binding domain (RBD) in samples from individuals receiving BNT162b2, mRNA-1273, and CoronaVac vaccines, stable binding was maintained against the full-length Omicron Spike protein. Compromised RBD binding IgG was accompanied by a loss of RBD-specific antibody Fc gamma receptor (Fe gamma R) binding in samples from individuals who received the CoronaVac vaccine, but RBD-specific Fc gamma R2a and Fc gamma R3a binding was preserved in recipients of mRNA vaccines. Conversely, Spike protein-specific antibodies exhibited persistent but reduced binding to Fc gamma Rs across all three vaccines, although higher binding was observed in samples from recipients of mRNA vaccines. This was associated with preservation of Fc gamma R2a and Fc gamma R3a binding antibodies and maintenance of Spike protein-specific antibody-dependent natural killer cell activation. Thus, despite the loss of Omicron neutralization, vaccine-induced Spike protein-specific antibodies continue to drive Fc effector functions, suggesting a capacity for extraneutralizing antibodies to contribute to disease control.
- ItemPreserved Omicron Spike specific antibody binding and Fc-recognition across COVID-19 vaccine platforms(2021) Bartsch, Y.; Tong, X.; Kang, J.; Alter, G.; Avendaño, María José; Serrano, Eileen F.; García-Salum, Tamara; Pardo-Roa, Catalina; Riquelme, Arnoldo; Medina, Rafael A.Despite the dramatic spread of Omicron globally, even among highly vaccinated populations, death rates have not increased concomitantly. These data argue that alternative immune mechanisms, beyond neutralization, may continue to confer protection against severe disease. Beyond their ability to bind and block infection, antibodies contribute to control and clearance of multiple infections via their ability to direct antiviral immunity via Fc-effector mechanisms. Thus, here we probed the ability of vaccine induced antibodies, across three COVID-19 vaccines, to drive Fc-effector activity against Omicron. Despite the significant loss of IgM, IgA and IgG binding to the Omicron Receptor Binding Domain (RBD) across BNT162b2, mRNA-1273, and CoronaVac vaccines, stable isotype binding was observed across all of these vaccines to the Omicron Spike. Compromised RBD binding IgG was accompanied by a significant loss of cross RBD-specific antibody Fcγ-receptor binding by the CoronaVac vaccine, but preservation of RBD-specific FcγR2a and Fcγ3a binding across the mRNA vaccines. Conversely, Spike-specific antibodies exhibited persistent binding to Fcγ-receptors, across all three vaccines, albeit higher binding was observed with the mRNA vaccines, marked by a selective preservation of FcγR2a and Fcγ3a binding antibodies. Thus, despite the significant to near complete loss of Omicron neutralization across several vaccine platforms against Omicron, vaccine induced Spike-specific antibodies continue to recognize the virus and recruit Fc-receptors pointing to a persistent capacity for extra-neutralizing antibodies to contribute Omicron disease attenuation.
- ItemSARS-CoV-2 infectivity and antigenic evasion: spotlight on isolated Omicron sub-lineages(2024) Barrera, Aldo; Martinez-Valdebenito, Constanza; Angulo, Jenniffer; Palma, Carlos; Hormazabal, Juan; Vial, Cecilia; Aguilera, Ximena; Castillo-Torres, Pablo; Pardo-Roa, Catalina; Balcells, Maria Elvira; Nervi, Bruno; Le Corre, Nicole; Ferres, MarcelaSince 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.
- ItemViral shedding dynamics reveals sputum as a reliable and cost-saving specimen for SARS-CoV-2 diagnosis within the first 10 days since symptom onset: A prospective cohort study(2020) Levican, Jorge; Almonacid, Leonardo I.; Valenzuela, Gonzalo; García-Salum, Tamara; Rojas, Luis; Serrano, Eileen; Pardo-Roa, Catalina; Salinas, Erick; Avendaño, María José; Perazzo, Fabiola; Díaz, Luis Antonio; Valderrama, Sebastián; Ortega, Marcos; Toro, Adriana; Montecinos, Viviana; Riquelme, Arnoldo; Medina, Rafael A.Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome virus (SARS-CoV-2) is challenging global public health, due to an increasing demand for testing and the shortage of diagnostic supplies. Nasopharyngeal swab (NPS) is considered the optimal sample for SARS-CoV2 diagnosis and sputum (SPT) has been proposed as an economic alternative. However, the temporal concordance of diagnosis in NPS and SPT has not been addressed. Methods: Through a longitudinal study we compared the shedding dynamics of SARS-CoV-2 RNA evaluated by RT-qPCR in serially collected SPT and NPS obtained from 82 ambulatory and hospitalized patients during acute infection and convalescence. The concordance during the follow-up and cost analysis between both collected specimens was evaluated. Findings: We analyzed 379 samples, 177 NPS and 202 SPT. The highest proportion of positive samples was detected within the first 15 days after the symptoms onset. The median time of positivity was higher for NPS (median= 25 days) than SPT (median= 21 days). There was no significant difference in the median RT-qPCR CT values between both sample types. The temporal categorization of matched-paired samples indicated substantial correlation (r=0·6023) and substantial agreement (87·23%) during the first ten days since symptoms onset (kappa = 0·697). A cost analysis demonstrated a significant saving when the SPT specimen was used. Interpretation: Sputum is a feasible and cost-saving alternative to NPS, providing an equivalent value for the detection and follow-up of SARS-CoV-2 RNA.