Browsing by Author "Medina, Rafael A."
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- ItemAntigenic characterization of novel H1 influenza A viruses in swine(2020) Tapia, Rodrigo; Torremorell, Montserrat; Culhane, Marie; Medina, Rafael A.; Neira, VictorNovel H1N2 influenza A viruses (IAVs) in swine have been identified in Chile co-circulating with pandemic H1N1 2009-like (A(H1N1)pdm09-like) viruses. The objective of this study was to characterize antigenically the swine H1 IAVs circulating in Chile. Genetic analysis based on the HA1 domain and antigenic analysis by hemagglutination inhibition assay were carried out. Three antigenic clusters were identified, named Chilean H1 A (ChH1A), Chilean H1 B (ChH1B), and A(H1N1)pdm09-like. The antigenic sites of ChH1A and ChH1B strains were 10-60% distant from those of commercial vaccine strains at the amino acid sequence level. Antigenic variants were identified within the clusters ChH1A and A(H1N1)pdm09-like. Substitutions in the main antigenic sites (E153G in Sa, Q193H in Sb, D168N in Ca1, P137S in Ca2, and F71L in Cb) were detected in variants from the ChH1A cluster, whereas only a single substitution in antigenic site Sa (G155E) was detected in variants from A(H1N1)pdm09-like cluster, which confirms the importance to carrying out antigenic analyses in addition to genetic analyses to evaluate control measures such as vaccination. These results highlight the need to update vaccines for swine in Chile and the importance of continued surveillance to determine the onward transmission of antigenic variants in Chilean pig populations.
- ItemAutoantibodies against type I IFNs in patients with critical influenza pneumonia(2022) Zhang, Qian; Pizzorno, Andres; Miorin, Lisa; Bastard, Paul; Gervais, Adrian; Le Voyer, Tom; Bizien, Lucy; Manry, Jeremy; Rosain, Jeremie; Philippot, Quentin; Goavec, Kelian; Padey, Blandine; Cupic, Anastasija; Laurent, Emilie; Saker, Kahina; Vanker, Martti; Saerekannu, Karita; Garcia-Salum, Tamara; Ferres, Marcela; Le Corre, Nicole; Sanchez-Cespedes, Javier; Balsera-Manzanero, Maria; Carratala, Jordi; Retamar-Gentil, Pilar; Abelenda-Alonso, Gabriela; Valiente, Adoracion; Tiberghien, Pierre; Zins, Marie; Debette, Stephanie; Meyts, Isabelle; Haerynck, Filomeen; Castagnoli, Riccardo; Notarangelo, Luigi D.; Gonzalez-Granado, Luis I.; Dominguez-Pinilla, Nerea; Andreakos, Evangelos; Triantafyllia, Vasiliki; Rodriguez-Gallego, Carlos; Sole-Violan, Jordi; Ruiz-Hernandez, Jose Juan; Rodriguez de Castro, Felipe; Ferreres, Jose; Briones, Marisa; Wauters, Joost; Vanderbeke, Lore; Feys, Simon; Kuo, Chen-Yen; Lei, Wei-Te; Ku, Cheng-Lung; Tal, Galit; Etzioni, Amos; Hanna, Suhair; Fournet, Thomas; Casalegno, Jean-Sebastien; Queromes, Gregory; Argaud, Laurent; Javouhey, Etienne; Rosa-Calatrava, Manuel; Cordero, Elisa; Aydillo, Teresa; Medina, Rafael A.; Kisand, Kai; Puel, Anne; Jouanguy, Emmanuelle; Abel, Laurent; Cobat, Aurelie; Trouillet-Assant, Sophie; Garcia-Sastre, Adolfo; Casanova, Jean-LaurentIn an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine.
- ItemCirculation patterns of human seasonal Influenza A viruses in Chile before H1N1pdm09 pandemic(2021) Mena, Juan; Tapia, Rodrigo; Verdugo, Claudio; Avendano, Luis; Parra-Castro, Paulina; Medina, Rafael A.; Barriga, Gonzalo; Neira, VictorUnderstanding the diversity and circulation dynamics of seasonal influenza viruses is key to public health decision-making. The limited genetic information of pre-pandemic seasonal IAVs in Chile has made it difficult to accurately reconstruct the phylogenetic relationships of these viruses within the country. The objective of this study was to determine the genetic diversity of pre-pandemic human seasonal IAVs in Chile. We sequenced the complete genome of 42 historic IAV obtained between 1996 and 2007. The phylogeny was determined using HA sequences and complemented using other segments. Time-scale phylogenetic analyses revealed that the diversity of pre-pandemic human seasonal IAVs in Chile was influenced by continuous introductions of new A/H1N1 and A/H3N2 lineages and constant viral exchange between Chile and other countries every year. These results provide important knowledge about genetic diversity and evolutionary patterns of pre-pandemic human seasonal IAVs in Chile, which can help design optimal surveillance systems and prevention strategies. However, future studies with current sequences should be conducted.
- ItemCross-protection of commercial vaccines against Chilean swine influenza A virus using the guinea pig model as a surrogate(2023) Tapia, Rodrigo; Mena, Juan; Garcia, Victoria; Culhane, Marie; Medina, Rafael A.; Neira, VictorInfluenza A virus poses a significant threat to public health and the swine industry. Vaccination is the primary measure for controlling the disease, but the effectiveness of vaccines can vary depending on the antigenic match between vaccine strains and circulating strains. In Chile, H1N1pdm09 and other lineages H1N2 and H3N2 have been detected in pigs, which are genetically distinct from the strains included in commercial vaccines. This study aimed to evaluate the cross-protection by commercial vaccines against strains circulating in Chile using the guinea pig model. For this study, four circulating strains [A/swine/Chile/H1A-7/2014(H1N2), A/swine/Chile/H1B-2/2014(H1N2), A/swine/Chile/H1P-12/2015(H1N1), and A/swine/Chile/H3-2/2015(H3N2)] were selected. Guinea pigs were divided into vaccinated and control groups. The vaccinated animals received either a multivalent antigenically heterologous or monovalent homologous vaccine, while the control animals remained unvaccinated. Following vaccination, all animals were intranasally challenged, and nasal wash samples were collected at different time points post-infection. The results showed that the homologous monovalent vaccine-induced hemagglutinin-specific antibodies against the Chilean pandemic H1N1pdm09 strain. However, the commercial heterologous multivalent vaccine failed to induce hemagglutinin-specific antibody titers against the H1N2 and H3N2 challenge strains. Furthermore, the homologous monovalent vaccine significantly reduced the duration of viral shedding and viral titers specifically against the Chilean pandemic H1N1pdm09 strain and heterologous multivalent vaccine only partial. These findings highlight the importance of regularly updating vaccine strains to match the circulating field strains for effective control of swine influenza. Further research is needed to develop vaccines that confer broader protection against diverse strains of swine influenza A virus.
- ItemDevelopment and Characterization of a Highly Specific and Sensitive SYBR Green Reverse Transcriptase PCR Assay for Detection of the 2009 Pandemic H1N1 Influenza Virus on the Basis of Sequence Signatures(AMER SOC MICROBIOLOGY, 2011) Medina, Rafael A.; Rojas, Mark; Tuin, Astrid; Huff, Stephen; Ferres, Marcela; Martinez Valdebenito, Constanza; Godoy, Paula; Garcia Sastre, Adolfo; Fofanov, Yuriy; SantaLucia, John, Jr.The emergence and rapid spread of the 2009 H1N1 pandemic influenza virus showed that many diagnostic tests were unsuitable for detecting the novel virus isolates. In most countries the probe-based TaqMan assay developed by the U.S. Centers for Disease Control and Prevention was used for diagnostic purposes. The substantial sequence data that became available during the course of the pandemic created the opportunity to utilize bioinformatics tools to evaluate the unique sequence properties of this virus for the development of diagnostic tests. We used a comprehensive computational approach to examine conserved 2009 H1N1 sequence signatures that are at least 20 nucleotides long and contain at least two mismatches compared to any other known H1N1 genome. We found that the hemagglutinin (HA) and neuraminidase (NA) genes contained sequence signatures that are highly conserved among 2009 H1N1 isolates. Based on the NA gene signatures, we used Visual-OMP to design primers with optimal hybridization affinity and we used ThermoBLAST to minimize amplification artifacts. This procedure resulted in a highly sensitive and discriminatory 2009 H1N1 detection assay. Importantly, we found that the primer set can be used reliably in both a conventional TaqMan and a SYBR green reverse transcriptase (RT)-PCR assay with no loss of specificity or sensitivity. We validated the diagnostic accuracy of the NA SYBR green assay with 125 clinical specimens obtained between May and August 2009 in Chile, and we showed diagnostic efficacy comparable to the CDC assay. Our approach highlights the use of systematic computational approaches to develop robust diagnostic tests during a viral pandemic.
- 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/)
- ItemNovel influenza A viruses in pigs with zoonotic potential, Chile(2024) Tapia, Rodrigo; Brito, Barbara; Saavedra, Marco; Mena, Juan; Garcia-Salum, Tamara; Rathnasinghe, Raveen; Barriga, Gonzalo; Tapia, Karla; Garcia, Victoria; Bucarey, Sergio; Jang, Yunho; Wentworth, David; Torremorell, Montserrat; Neira, Victor; Medina, Rafael A.Novel H1N2 and H3N2 swine influenza A viruses (IAVs) have recently been identified in Chile. The objective of this study was to evaluate their zoonotic potential. We perform phylogenetic analyses to determine the genetic origin and evolution of these viruses, and a serological analysis to determine the level of cross-protective antibodies in the human population. Eight genotypes were identified, all with pandemic H1N1 2009-like internal genes. H1N1 and H1N2 were the subtypes more commonly detected. Swine H1N2 and H3N2 IAVs had hemagglutinin and neuraminidase lineages genetically divergent from IAVs reported worldwide, including human vaccine strains. These genes originated from human seasonal viruses were introduced into the swine population since the mid-1980s. Serological data indicate that the general population is susceptible to the H3N2 virus and that elderly and young children also lack protective antibodies against the H1N2 strains, suggesting that these viruses could be potential zoonotic threats. Continuous IAV surveillance and monitoring of the swine and human populations is strongly recommended.IMPORTANCEIn the global context, where swine serve as crucial intermediate hosts for influenza A viruses (IAVs), this study addresses the pressing concern of the zoonotic potential of novel reassortant strains. Conducted on a large scale in Chile, it presents a comprehensive account of swine influenza A virus diversity, covering 93.8% of the country's industrialized swine farms. The findings reveal eight distinct swine IAV genotypes, all carrying a complete internal gene cassette of pandemic H1N1 2009 origin, emphasizing potential increased replication and transmission fitness. Genetic divergence of H1N2 and H3N2 IAVs from globally reported strains raises alarms, with evidence suggesting introductions from human seasonal viruses since the mid-1980s. A detailed serological analysis underscores the zoonotic threat, indicating susceptibility in the general population to swine H3N2 and a lack of protective antibodies in vulnerable demographics. These data highlight the importance of continuous surveillance, providing crucial insights for global health organizations.
- 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.
- ItemPhantosmia May Predict Long‐Term Measurable Olfactory Dysfunction After COVID‐19(WILEY, 2022) Aliaga Durán, Rodrigo Francisco; Callejas Canepa, Claudio Andrés; Cordano Guajardo Valentina Paz; Díaz, Luis Antonio; Fuentes López, Eduardo; García Huidobro, Francisco Gustavo; García Salum, Tamara; González G, Claudia; Lagos Villaseca, Antonia Elisa; Leung Caballero, Jai-sen Francisco; Medina, Rafael A.; Palmer, James N.Objectives Persistent olfactory dysfunction (OD) after 6 months caused by SARS-CoV-2 infection has been reported with a variable prevalence worldwide. This study aimed to determine the prevalence of long-term OD and identify predisposing factors. Methods
- 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.
- ItemTracking the emergence of antigenic variants in influenza A virus epidemics in Brazil(2023) Pillai, Tara K.; Johnson, Katherine E.; Song, Timothy; Gregianini, Tatiana S.; Tatiana, G. Baccin; Wang, Guojun; Medina, Rafael A.; Van Bakel, Harm; Garcia-Sastre, Adolfo; Nelson, Martha, I; Ghedin, Elodie; Veiga, Ana B. G.Influenza A virus (IAV) circulation patterns differ in North America and South America, with influenza seasons often characterized by different subtypes and strains. However, South America is relatively undersampled considering the size of its population. To address this gap, we sequenced the complete genomes of 220 IAVs collected between 2009 and 2016 from hospitalized patients in southern Brazil. New genetic drift variants were introduced into southern Brazil each season from a global gene pool, including four H3N2 clades (3c, 3c2, 3c3, and 3c2a) and five H1N1pdm clades (clades 6, 7, 6b, 6c, and 6b1). In 2016, H1N1pdm viruses belonging to a new 6b1 clade caused a severe influenza epidemic in southern Brazil that arrived early and spread rapidly, peaking mid-autumn. Inhibition assays showed that the A/California/07/2009(H1N1) vaccine strain did not protect well against 6b1 viruses. Phylogenetically, most 6b1 sequences that circulated in southern Brazil belong to a single transmission cluster that rapidly diffused across susceptible populations, leading to the highest levels of influenza hospitalization and mortality seen since the 2009 pandemic. Continuous genomic surveillance is needed to monitor rapidly evolving IAVs for vaccine strain selection and understand their epidemiological impact in understudied regions.
- ItemUbiquitous influenza A virus in Chilean swine before the H1N1pdm09 introduction(2021) Mena, Juan; Ariyama, Naomi; Navarro, Camila; Quezada, Manuel; Brevis, Cristina; Rojas, Daniela; Medina, Rafael A.; Brito, Barbara; Ruiz, Alvaro; Neira, VictorInfluenza A virus (IAV) was a neglected swine pathogen in South America before the 2009 H1N1 pandemic (A(H1N1)pdm2009). The A(H1N1)pdm2009 strain has widely spread among the Chilean swine population and co-circulates with endemic H1N2 and H3N2 viruses. The presence of IAV as a swine pathogen in Chilean swine before the 2009 pandemic is unknown. To understand the IAV in swine prior to 2009, aY retrospective study of samples from pigs affected with respiratory diseases was conducted. Ninety formalin-fixed and paraffin-embedded lung tissues belonging to 21 intensive pig production companies located in five different administrative regions of Chile, collected between 2005 and 2008, were evaluated. The tissues were tested by immunohistochemistry (IHC), identifying that 9 out of 21 farms (42.8%) and 31 out of 90 (34.4%) samples were IAV positive. Only three out of the 31 IHC-positive samples were positive upon RNA extraction and rtRT-PCR analysis. Partial nucleotide sequences were obtained from one sample and characterized as an H3N2 subtype closely related to a human seasonal H3N2 IAVs that circulated globally in the mid-90s. These results indicate that IAV was circulating in swine before 2009 and highlight the value of conducting retrospective studies through genomic strategies to analyse historical samples.
- 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.