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1. Immunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infection

Author

Ávila-Nieto, Carlos, Vergara-Alert, Júlia, Amengual-Rigo, Pep, Ainsua-Enrich, Erola, Brustolin, Marco, Rodríguez de la Concepción, María Luisa, Pedreño-Lopez, Núria, Rodon, Jordi, Urrea, Victor, Pradenas, Edwards, Marfil, Silvia, Ballana, Ester, Riveira-Muñoz, Eva, Pérez, Mònica, Roca, Núria, Tarrés-Freixas, Ferran, Cantero, Guillermo, Pons-Grífols, Anna, Rovirosa, Carla, Aguilar-Gurrieri, Carmen, Ortiz, Raquel, Barajas, Ana, Trinité, Benjamin, Lepore, Rosalba, Muñoz-Basagoiti, Jordana, Perez-Zsolt, Daniel, Izquierdo-Useros, Nuria, Valencia, Alfonso, Blanco, Julià, Guallar, Victor, Clotet, Bonaventura, Segalés, Joaquim, and Carrillo, Jorge

Published
2024
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2. Immunisation efficacy of a stabilised SARS-CoV-2 spike glycoprotein in two geriatric animal models

Author

Usai, Carla, Ainsua-Enrich, Erola, Gales, Victor Urrea, Pradenas, Edwards, Lorca-Oró, Cristina, Tarrés-Freixas, Ferran, Roca, Núria, Pérez, Mónica, Ávila-Nieto, Carlos, Rodríguez de la Concepción, María Luisa, Pedreño-Lopez, Núria, Carabelli, Julieta, Trinité, Benjamin, Ballana, Ester, Riveira-Muñoz, Eva, Izquierdo-Useros, Nuria, Clotet, Bonaventura, Blanco, Julià, Guallar, Victor, Cantero, Guillermo, Vergara-Alert, Júlia, Carrillo, Jorge, and Segalés, Joaquim

Published
2024
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3. A monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity

Author

de Campos-Mata, Leire, Trinité, Benjamin, Modrego, Andrea, Tejedor Vaquero, Sonia, Pradenas, Edwards, Pons-Grífols, Anna, Rodrigo Melero, Natalia, Carlero, Diego, Marfil, Silvia, Santiago, César, Raïch-Regué, Dàlia, Bueno-Carrasco, María Teresa, Tarrés-Freixas, Ferran, Abancó, Ferran, Urrea, Victor, Izquierdo-Useros, Nuria, Riveira-Muñoz, Eva, Ballana, Ester, Pérez, Mónica, Vergara-Alert, Júlia, Segalés, Joaquim, Carolis, Carlo, Arranz, Rocío, Blanco, Julià, and Magri, Giuliana

Published
2024
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4. Virus-like particle-mediated delivery of structure-selected neoantigens demonstrates immunogenicity and antitumoral activity in mice

Author

Barajas, Ana, Amengual-Rigo, Pep, Pons-Grífols, Anna, Ortiz, Raquel, Gracia Carmona, Oriol, Urrea, Victor, de la Iglesia, Nuria, Blanco-Heredia, Juan, Anjos-Souza, Carla, Varela, Ismael, Trinité, Benjamin, Tarrés-Freixas, Ferran, Rovirosa, Carla, Lepore, Rosalba, Vázquez, Miguel, de Mattos-Arruda, Leticia, Valencia, Alfonso, Clotet, Bonaventura, Aguilar-Gurrieri, Carmen, Guallar, Victor, Carrillo, Jorge, and Blanco, Julià

Published
2024
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6. An engineered HIV-1 Gag-based VLP displaying high antigen density induces strong antibody-dependent functional immune responses

Author

Tarrés-Freixas, Ferran, Aguilar-Gurrieri, Carmen, Rodríguez de la Concepción, María Luisa, Urrea, Victor, Trinité, Benjamin, Ortiz, Raquel, Pradenas, Edwards, Blanco, Pau, Marfil, Sílvia, Molinos-Albert, Luis Manuel, Barajas, Ana, Pons-Grífols, Anna, Ávila-Nieto, Carlos, Varela, Ismael, Cervera, Laura, Gutiérrez-Granados, Sònia, Segura, María Mercedes, Gòdia, Francesc, Clotet, Bonaventura, Carrillo, Jorge, and Blanco, Julià

Published
2023
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8. Impact of hybrid immunity booster vaccination and Omicron breakthrough infection on SARS-CoV-2 VOCs cross-neutralization

Author

Pradenas, Edwards, Marfil, Silvia, Urrea, Víctor, Trigueros, Macedonia, Pidkova, Tetyana, Pons-Grífols, Anna, Ortiz, Raquel, Rovirosa, Carla, Tarrés-Freixas, Ferran, Aguilar-Gurrieri, Carmen, Toledo, Ruth, Chamorro, Anna, Noguera-Julian, Marc, Mateu, Lourdes, Blanco, Ignacio, Grau, Eulàlia, Massanella, Marta, Carrillo, Jorge, Clotet, Bonaventura, Trinité, Benjamin, and Blanco, Julià

Published
2023
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9. Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2

Author

Barreiro, Antonio, Prenafeta, Antoni, Bech-Sabat, Gregori, Roca, Mercè, Perozo Mur, Eva, March, Ricard, González-González, Luis, Madrenas, Laia, Corominas, Júlia, Fernández, Alex, Moros, Alexandra, Cañete, Manuel, Molas, Mercè, Pentinat-Pelegrin, Thais, Panosa, Clara, Moreno, Alberto, Puigvert Molas, Ester, Pol Vilarrassa, Eva, Palmada, Jordi, Garriga, Carme, Prat Cabañas, Teresa, Iglesias-Fernández, Javier, Vergara-Alert, Júlia, Lorca-Oró, Cristina, Roca, Núria, Fernández-Bastit, Leira, Rodon, Jordi, Pérez, Mònica, Segalés, Joaquim, Pradenas, Edwards, Marfil, Silvia, Trinité, Benjamin, Ortiz, Raquel, Clotet, Bonaventura, Blanco, Julià, Díaz Pedroza, Jorge, Ampudia Carrasco, Rosa, Rosales Salgado, Yaiza, Loubat-Casanovas, Jordina, Capdevila Larripa, Sara, Prado, Julia Garcia, Barretina, Jordi, Sisteré-Oró, Marta, Cebollada Rica, Paula, Meyerhans, Andreas, and Ferrer, Laura

Published
2023
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10. Kinetics of immune responses elicited after three mRNA COVID-19 vaccine doses in predominantly antibody-deficient individuals

Author

Ainsua-Enrich, Erola, Pedreño-Lopez, Núria, Bracke, Carmen, Ávila-Nieto, Carlos, Rodríguez de la Concepción, María Luisa, Pradenas, Edwards, Trinité, Benjamin, Marfil, Silvia, Miranda, Cristina, González, Sandra, Toledo, Ruth, Font, Marta, Benet, Susana, Escribà, Tuixent, Jimenez-Moyano, Esther, Peña, Ruth, Cedeño, Samandhy, Prado, Julia G., Mothe, Beatriz, Brander, Christian, Izquierdo-Useros, Nuria, Vergara-Alert, Julia, Segalés, Joaquim, Massanella, Marta, Benitez, Rosa María, Romero, Alba, Molina-Morant, Daniel, Blanco, Julià, Clotet, Bonaventura, Mateu, Lourdes, Pedro-Botet, María Luisa, and Carrillo, Jorge

Published
2022
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11. Glucocorticoids’ treatment impairs the medium-term immunogenic response to SARS-CoV-2 mRNA vaccines in Systemic Lupus Erythematosus patients

Author

Garcia-Cirera, Silvia, Calvet, Joan, Berenguer-Llergo, Antoni, Pradenas, Edwards, Marfil, Silvia, Massanella, Marta, Mateu, Lourdes, Trinité, Benjamin, Llop, Maria, Arévalo, Marta, Galisteo, Carlos, Orellana, Cristóbal, Gómez, Rafael, Gómez-Gerique, María Nieves, Carmona, Inma, Clotet, Bonaventura, Blanco, Julià, and Gratacós, Jordi

Published
2022
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12. High-titre methylene blue-treated convalescent plasma as an early treatment for outpatients with COVID-19: a randomised, placebo-controlled trial

Author

Ferrer, Susana, Gallardo, Mireia, Ubals, Maria, González-Beiras, Camila, Vall-Mayans, Martí, Suñer, Clara, Laporte-Villar, Clàudia, Nieto, Aroa, Comas-Leon, Xavier, Jiménez, Zahida, Ramírez-Viaplana, Ferran, Delgado-Capel, Maria, Díez Sánchez, Beatriz, Pons Barber, Maria, Gonzalez Ruiz, Cristian, Navarrete Gonzalez, Laura, González García, David, Vivero Larraza, Ainhoa, Carceles Peiró, Victor, Roquer López, Clàudia, Robert, Neus, Palet, Carles, Gudiol, Carlota, Casares Gonzalez, Pablo, Arcos Vila, Gemma, Flores Aguilera, Begoña, Rodríguez-Sevilla, Graciela, Dastis Arias, Macarena, Roca Font, Judit, Carrasco Matos, Katherine M., Saüch Valmaña, Glòria, Vidal Obradors, Carla, Tarres García, Silvia, Curriu Sabatès, Margarida, Nieto Rodríguez, Raquel, Línio, Rosa, Fornos, Míriam, Casamitjana, Natàlia, Alonso, Eva, Martínez, Núria, Maglio, Laura Analía, Comellas Fernandez, Laura, Garcia, Nadia, Hernández, Luis, González, Maria Isabel, Bravo, Anna, García, Yolanda, Sauleda Oliveras, Silvia, Vertiz, Tatiana, Benavent, Sergio, Bianco, Andrea Sofia, Verdaguer, Joaquim, Briones Zambrano, Ney Nicanor, Viozquez Meya, Maria, Hernández, Águeda, Casaña Lopez, Cristina, Bordoy, Antoni E., González Soler, Victoria, Giménez, Montserrat, París, Alexa, Marfil, Silvia, Trinité, Benjamin, Grau, Eulàlia, Alemany, Andrea, Millat-Martinez, Pere, Corbacho-Monné, Marc, Malchair, Pierre, Ouchi, Dan, Ruiz-Comellas, Anna, Ramírez-Morros, Anna, Rodríguez Codina, Joana, Amado Simon, Rosa, Videla, Sebastian, Costes, Gèlia, Capdevila-Jáuregui, Mar, Torrano-Soler, Pamela, San José, Alba, Bonet Papell, Glòria, Puig, Jordi, Otero, Aurema, Ruibal Suarez, Jose Carlos, Zarauza Pellejero, Alvaro, Llopis Roca, Ferran, Rodriguez Cortez, Orlando, Garcia Garcia, Vanesa, Vidal-Alaball, Josep, Millan, Anna, Contreras, Enric, Grifols, Joan-Ramon, Ancochea, Àgueda, Galvan-Femenia, Ivan, Piccolo Ferreira, Francini, Bonet, Mireia, Cantoni, Jordi, Prat, Núria, Ara, Jordi, Forcada Arcarons, Anna, Farré, Magí, Pradenas, Edwards, Blanco, Julià, Àngel Rodriguez-Arias, Miquel, Fernández Rivas, Gema, Marks, Michael, Bassat, Quique, Blanco, Ignacio, Baro, Bàrbara, Clotet, Bonaventura, and Mitjà, Oriol

Published
2022
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13. Clinical course impacts early kinetics,magnitude, and amplitude of SARS-CoV-2 neutralizing antibodies beyond 1 year after infection

Author

Pradenas, Edwards, Trinité, Benjamin, Urrea, Víctor, Marfil, Silvia, Tarrés-Freixas, Ferran, Ortiz, Raquel, Rovirosa, Carla, Rodon, Jordi, Vergara-Alert, Júlia, Segalés, Joaquim, Guallar, Victor, Valencia, Alfonso, Izquierdo-Useros, Nuria, Noguera-Julian, Marc, Carrillo, Jorge, Paredes, Roger, Mateu, Lourdes, Chamorro, Anna, Toledo, Ruth, Massanella, Marta, Clotet, Bonaventura, and Blanco, Julià

Published
2022
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14. Omicron XBB.1.16-Adapted Vaccine for COVID-19: Interim Immunogenicity and Safety Clinical Trial Results.

Author

López Fernández, María Jesús, Narejos, Silvia, Castro, Antoni, Echave-Sustaeta, José María, Forner, María José, Arana-Arri, Eunate, Molto, José, Bernad, Laia, Pérez-Caballero, Raúl, Prado, Julia G., Raïch-Regué, Dàlia, Boreika, Rytis, Izquierdo-Useros, Nuria, Trinité, Benjamin, Blanco, Julià, Puig-Barberà, Joan, and Natalini Martínez, Silvina

Subjects
COVID-19, SARS-CoV-2 Omicron variant, BOOSTER vaccines, COVID-19 pandemic, COVID-19 vaccines
Abstract

(1) Background: The global coronavirus disease 2019 vaccination adapts to protect populations from emerging variants. This communication presents interim findings from the new Omicron XBB.1.16-adapted PHH-1V81 protein-based vaccine compared to an XBB.1.5-adapted mRNA vaccine against various acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains. (2) Methods: In a Phase IIb/III pivotal trial, adults previously vaccinated with a primary scheme and at least one booster dose of an EU-approved mRNA vaccine randomly received either the PHH-1V81 or BNT162b2 XBB.1.5 vaccine booster as a single dose. The primary efficacy endpoint assessed neutralization titers against the Omicron XBB.1.16 variant at day 14. Secondary endpoints evaluated neutralization titers and cellular immunity against different variants. Safety endpoints comprised solicited reactions up to day 7 post-vaccination and serious adverse events until the cut-off date of the interim analysis. Changes in humoral responses were assessed by pseudovirion-based or virus neutralization assays. (3) Results: At the cut-off date, immunogenicity assessments included 599 participants. Both boosters elicited neutralizing antibodies against XBB.1.16, XBB.1.5, and JN.1, with PHH-1V81 inducing a higher response for all variants. The PHH-1V8 booster triggers a superior neutralizing antibody response against XBB variants compared to the mRNA vaccine. A subgroup analysis consistently revealed higher neutralizing antibody responses with PHH-1V81 across age groups, SARS-CoV-2 infection history, and the number of prior vaccination shots. A safety analysis (n = 607) at the day 14 visit revealed favorable safety profiles without any serious vaccine-related adverse events. (4) Conclusions: PHH-1V81 demonstrates superiority on humoral immunogenicity compared to the mRNA vaccine against XBB variants and non-inferiority against JN.1 with a favorable safety profile and lower reactogenicity, confirming its potential as a vaccine candidate. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Humoral and cellular immune responses after 6 months of a heterologous SARS-CoV-2 booster with the protein-based PHH-1V vaccine in a phase IIb trial

Author

Corominas, Júlia, primary, Garriga, Carme, additional, Prenafeta, Antoni, additional, Moros, Alexandra, additional, Cañete, Manuel, additional, Barreiro, Antonio, additional, González-González, Luis, additional, Madrenas, Laia, additional, Güell, Irina, additional, Clotet, Bonaventura, additional, Izquierdo-Useros, Nuria, additional, Raïch-Regué, Dàlia, additional, Gallemí, Marçal, additional, Blanco, Julià, additional, Pradenas, Edwards, additional, Trinité, Benjamin, additional, Prado, Julia G, additional, Pérez-Caballero, Raúl, additional, Bernad, Laia, additional, Plana, Montserrat, additional, Esteban, Ignasi, additional, Aurrecoechea, Elena, additional, Taleb, Rachel Abu, additional, McSkimming, Paula, additional, Soriano, Alex, additional, Nava, Jocelyn, additional, Anagua, Jesse Omar, additional, Ramos, Rafel, additional, Lluch, Ruth Martí, additional, Comes, Aida Corpes, additional, Romero, Susana Otero, additional, Martínez-Gómez, Xavier, additional, Camacho-Arteaga, Lina, additional, Molto, Jose, additional, Benet, Susana, additional, Bailón, Lucía, additional, Arribas, Jose R, additional, Borobia, Alberto M, additional, Parada, Javier Queiruga, additional, Navarro-Pérez, Jorge, additional, Giner, Maria José Forner, additional, Lucas, Rafael Ortí, additional, Jiménez, María del Mar Vázquez, additional, Fernández, María Jesús López, additional, Alvarez-Mon, Melchor, additional, Troncoso, Daniel, additional, Arana-Arri, Eunate, additional, Meijide, Susana, additional, Imaz-Ayo, Natale, additional, García, Patricia Muñoz, additional, de la Villa, Sofía, additional, Fernández, Sara Rodríguez, additional, Prat, Teresa, additional, Torroella, Èlia, additional, and Ferrer, Laura, additional

Published
2024
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17. HIV-1 latency and virus production from unintegrated genomes following direct infection of resting CD4 T cells

Author

Chan, Chi N, Trinité, Benjamin, Lee, Caroline S, Mahajan, Saurabh, Anand, Akanksha, Wodarz, Dominik, Sabbaj, Steffanie, Bansal, Anju, Goepfert, Paul A, and Levy, David N

Subjects
Microbiology, Biological Sciences, HIV/AIDS, Clinical Research, Infectious Diseases, 2.1 Biological and endogenous factors, Aetiology, 2.2 Factors relating to the physical environment, Infection, Adult, CD4-Positive T-Lymphocytes, Cells, Cultured, DNA, Viral, Gene Expression Profiling, HIV-1, Humans, Transcription, Genetic, Virus Latency, Virus Replication, Latency, Unintegrated DNA, Raltegravir, Integration, Cytotoxic T cells, Clinical Sciences, Virology
Abstract

BackgroundHIV-1 integration is prone to a high rate of failure, resulting in the accumulation of unintegrated viral genomes (uDNA) in vivo and in vitro. uDNA can be transcriptionally active, and circularized uDNA genomes are biochemically stable in non-proliferating cells. Resting, non-proliferating CD4 T cells are prime targets of HIV-1 infection and latently infected resting CD4 T cells are the major barrier to HIV cure. Our prior studies demonstrated that uDNA generates infectious virions when T cell activation follows rather than precedes infection.ResultsHere, we characterize in primary resting CD4 T cells the dynamics of integrated and unintegrated virus expression, genome persistence and sensitivity to latency reversing agents. Unintegrated HIV-1 was abundant in directly infected resting CD4 T cells. Maximal gene expression from uDNA was delayed compared with integrated HIV-1 and was less toxic, resulting in uDNA enrichment over time relative to integrated proviruses. Inhibiting integration with raltegravir shunted the generation of durable latency from integrated to unintegrated genomes. Latent uDNA was activated to de novo virus production by latency reversing agents that also activated latent integrated proviruses, including PKC activators, histone deacetylase inhibitors and P-TEFb agonists. However, uDNA responses displayed a wider dynamic range, indicating differential regulation of expression relative to integrated proviruses. Similar to what has recently been demonstrated for latent integrated proviruses, one or two applications of latency reversing agents failed to activate all latent unintegrated genomes. Unlike integrated proviruses, uDNA gene expression did not down modulate expression of HLA Class I on resting CD4 T cells. uDNA did, however, efficiently prime infected cells for killing by HIV-1-specific cytotoxic T cells.ConclusionsThese studies demonstrate that contributions by unintegrated genomes to HIV-1 gene expression, virus production, latency and immune responses are inherent properties of the direct infection of resting CD4 T cells. Experimental models of HIV-1 latency employing directly infected resting CD4 T cells should calibrate the contribution of unintegrated HIV-1.

Published
2016

18. SARS-CoV-2 interaction with Siglec-1 mediates trans-infection by dendritic cells

Author

Perez-Zsolt, Daniel, Muñoz-Basagoiti, Jordana, Rodon, Jordi, Elosua-Bayes, Marc, Raïch-Regué, Dàlia, Risco, Cristina, Sachse, Martin, Pino, Maria, Gumber, Sanjeev, Paiardini, Mirko, Chojnacki, Jakub, Erkizia, Itziar, Muñiz-Trabudua, Xabier, Ballana, Ester, Riveira-Muñoz, Eva, Noguera-Julian, Marc, Paredes, Roger, Trinité, Benjamin, Tarrés-Freixas, Ferran, Blanco, Ignacio, Guallar, Victor, Carrillo, Jorge, Blanco, Julià, Telenti, Amalio, Heyn, Holger, Segalés, Joaquim, Clotet, Bonaventura, Martinez-Picado, Javier, Vergara-Alert, Júlia, and Izquierdo-Useros, Nuria

Published
2021
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19. Author Correction to: SARS-CoV-2 interaction with Siglec-1 mediates trans-infection by dendritic cells

Author

Perez-Zsolt, Daniel, Muñoz-Basagoiti, Jordana, Rodon, Jordi, Elosua-Bayes, Marc, Raïch-Regué, Dàlia, Risco, Cristina, Sachse, Martin, Pino, Maria, Gumber, Sanjeev, Paiardini, Mirko, Chojnacki, Jakub, Erkizia, Itziar, Muñiz-Trabudua, Xabier, Ballana, Ester, Riveira-Muñoz, Eva, Noguera-Julian, Marc, Paredes, Roger, Trinité, Benjamin, Tarrés-Freixas, Ferran, Blanco, Ignacio, Guallar, Victor, Carrillo, Jorge, Blanco, Julià, Telenti, Amalio, Heyn, Holger, Segalés, Joaquim, Clotet, Bonaventura, Martinez-Picado, Javier, Vergara-Alert, Júlia, and Izquierdo-Useros, Nuria

Published
2022
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20. Production and Immunogenicity of FeLV Gag-Based VLPs Exposing a Stabilized FeLV Envelope Glycoprotein.

Author

Ortiz, Raquel, Barajas, Ana, Pons-Grífols, Anna, Trinité, Benjamin, Tarrés-Freixas, Ferran, Rovirosa, Carla, Urrea, Víctor, Barreiro, Antonio, Gonzalez-Tendero, Anna, Rovira-Rigau, Maria, Cardona, Maria, Ferrer, Laura, Clotet, Bonaventura, Carrillo, Jorge, Aguilar-Gurrieri, Carmen, and Blanco, Julià

Subjects
FELINE leukemia virus, IMMUNE response, GLYCOPROTEINS, HUMORAL immunity, MEMBRANE proteins, DNA vaccines, VIRAL envelope proteins
Abstract

The envelope glycoprotein (Env) of retroviruses, such as the Feline leukemia virus (FeLV), is the main target of neutralizing humoral response, and therefore, a promising vaccine candidate, despite its reported poor immunogenicity. The incorporation of mutations that stabilize analogous proteins from other viruses in their prefusion conformation (e.g., HIV Env, SARS-CoV-2 S, or RSV F glycoproteins) has improved their capability to induce neutralizing protective immune responses. Therefore, we have stabilized the FeLV Env protein following a strategy based on the incorporation of a disulfide bond and an Ile/Pro mutation (SOSIP) previously used to generate soluble HIV Env trimers. We have characterized this SOSIP-FeLV Env in its soluble form and as a transmembrane protein present at high density on the surface of FeLV Gag-based VLPs. Furthermore, we have tested its immunogenicity in DNA-immunization assays in C57BL/6 mice. Low anti-FeLV Env responses were detected in SOSIP-FeLV soluble protein-immunized animals; however, unexpectedly no responses were detected in the animals immunized with SOSIP-FeLV Gag-based VLPs. In contrast, high humoral response against FeLV Gag was observed in the animals immunized with control Gag VLPs lacking SOSIP-FeLV Env, while this response was significantly impaired when the VLPs incorporated SOSIP-FeLV Env. Our data suggest that FeLV Env can be stabilized as a soluble protein and can be expressed in high-density VLPs. However, when formulated as a DNA vaccine, SOSIP-FeLV Env remains poorly immunogenic, a limitation that must be overcome to develop an effective FeLV vaccine. [ABSTRACT FROM AUTHOR]

Published
2024
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21. Novel Spike-stabilized trimers with improved production protect K18-hACE2 mice and golden Syrian hamsters from the highly pathogenic SARS-CoV-2 Beta variant

Author

Ávila-Nieto, Carlos, primary, Vergara-Alert, Júlia, additional, Amengual-Rigo, Pep, additional, Ainsua-Enrich, Erola, additional, Brustolin, Marco, additional, Rodríguez de la Concepción, María Luisa, additional, Pedreño-Lopez, Núria, additional, Rodon, Jordi, additional, Urrea, Victor, additional, Pradenas, Edwards, additional, Marfil, Silvia, additional, Ballana, Ester, additional, Riveira-Muñoz, Eva, additional, Pérez, Mònica, additional, Roca, Núria, additional, Tarrés-Freixas, Ferran, additional, Carabelli, Julieta, additional, Cantero, Guillermo, additional, Pons-Grífols, Anna, additional, Rovirosa, Carla, additional, Aguilar-Gurrieri, Carmen, additional, Ortiz, Raquel, additional, Barajas, Ana, additional, Trinité, Benjamin, additional, Lepore, Rosalba, additional, Muñoz-Basagoiti, Jordana, additional, Perez-Zsolt, Daniel, additional, Izquierdo-Useros, Nuria, additional, Valencia, Alfonso, additional, Blanco, Julià, additional, Clotet, Bonaventura, additional, Guallar, Victor, additional, Segalés, Joaquim, additional, and Carrillo, Jorge, additional

Published
2023
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22. Efficacy and safety of mRNA1273 SARS-CoV-2 vaccination in hematopoietic stem cell transplant recipients: Single center experience

Author

Huguet, Maria, primary, Boigues, Marc, additional, Sorigué, Marc, additional, Blanco, Julià, additional, Quirant, Bibiana, additional, Ferrà, Christelle, additional, Huguet, Maria, additional, Morgades, Mireia, additional, Felip, Eudald, additional, Morán, Teresa, additional, Pradenas, Edwards, additional, Marfil, Silvia, additional, Trinité, Benjamin, additional, Torrent, Anna, additional, Abril, Laura, additional, and Sancho, Juan-Manuel, additional

Published
2023
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23. Seven-month kinetics of SARS-CoV-2 antibodies and role of pre-existing antibodies to human coronaviruses

Author

Ortega, Natalia, Ribes, Marta, Vidal, Marta, Rubio, Rocío, Aguilar, Ruth, Williams, Sarah, Barrios, Diana, Alonso, Selena, Hernández-Luis, Pablo, Mitchell, Robert A., Jairoce, Chenjerai, Cruz, Angeline, Jimenez, Alfons, Santano, Rebeca, Méndez, Susana, Lamoglia, Montserrat, Rosell, Neus, Llupià, Anna, Puyol, Laura, Chi, Jordi, Melero, Natalia Rodrigo, Parras, Daniel, Serra, Pau, Pradenas, Edwards, Trinité, Benjamin, Blanco, Julià, Mayor, Alfredo, Barroso, Sonia, Varela, Pilar, Vilella, Anna, Trilla, Antoni, Santamaria, Pere, Carolis, Carlo, Tortajada, Marta, Izquierdo, Luis, Angulo, Ana, Engel, Pablo, García-Basteiro, Alberto L., Moncunill, Gemma, and Dobaño, Carlota

Published
2021
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24. SARS-CoV-2 infection elicits a rapid neutralizing antibody response that correlates with disease severity

Author

Trinité, Benjamin, Tarrés-Freixas, Ferran, Rodon, Jordi, Pradenas, Edwards, Urrea, Víctor, Marfil, Silvia, Rodríguez de la Concepción, María Luisa, Ávila-Nieto, Carlos, Aguilar-Gurrieri, Carmen, Barajas, Ana, Ortiz, Raquel, Paredes, Roger, Mateu, Lourdes, Valencia, Alfonso, Guallar, Víctor, Ruiz, Lidia, Grau, Eulàlia, Massanella, Marta, Puig, Jordi, Chamorro, Anna, Izquierdo-Useros, Nuria, Segalés, Joaquim, Clotet, Bonaventura, Carrillo, Jorge, Vergara-Alert, Júlia, and Blanco, Julià

Published
2021
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25. On the Laws of Virus Spread through Cell Populations

Author

Wodarz, Dominik, Chan, Chi N, Trinité, Benjamin, Komarova, Natalia L, and Levy, David N

Subjects
Infectious Diseases, HIV/AIDS, Vaccine Related, Aetiology, 2.2 Factors relating to the physical environment, Infection, Good Health and Well Being, HIV-1, Humans, Jurkat Cells, Models, Theoretical, T-Lymphocytes, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology
Abstract

UnlabelledThe dynamics of viral infections have been investigated extensively, often with a combination of experimental and mathematical approaches. Mathematical descriptions of virus spread through cell populations are well established in the literature and have yielded important insights, yet the formulation of certain fundamental aspects of virus dynamics models remains uncertain and untested. Here, we investigate the process of infection and, in particular, the effect of varying the target cell population size on the number of productively infected cells generated. Using an in vitro single-round HIV-1 infection system, we find that the established modeling framework cannot accurately fit the data. If the model is fit to data with the lowest number of cells and is used to predict data generated with larger cell populations, the model significantly overestimates the number of productively infected cells generated. Interestingly, this deviation becomes stronger under experimental conditions that promote mixing of cells and viruses. The reason for the deviation is that the standard model makes certain oversimplifying assumptions about the fate of viruses that fail to find a cell in their immediate proximity. We derive from stochastic processes a different model that assumes simultaneous access of the virus to multiple target cells. In this scenario, if no cell is available to the virus at its location, it has a chance to interact with other cells, a process that can be promoted by mixing of the populations. This model can accurately fit the experimental data and suggests a new interpretation of mass action in virus dynamics models.ImportanceUnderstanding the principles of virus growth through cell populations is of fundamental importance to virology. It helps us make informed decisions about intervention strategies aimed at preventing virus growth, such as drug treatment or vaccination approaches, e.g., in HIV infection, yet considerable uncertainty remains in this respect. An important variable in this context is the number of susceptible cells available for virus replication. How does the number of susceptible cells influence the growth potential of the virus? Besides the importance of such information for clinical responses, a thorough understanding of this is also important for the prediction of virus levels in patients and the estimation of crucial patient parameters through the use of mathematical models. This paper investigates the relationship between target cell availability and the virus growth potential with a combination of experimental and mathematical approaches and provides significant new insights.

Published
2014

26. VLP-mediated delivery of structure-selected neoantigens demonstrates immunogenicity and antitumoral activity in mice

Author

Barajas, Ana, primary, Amengual-Rigo, Pep, additional, Pons-Grifols, Anna, additional, Ortiz, Raquel, additional, Garcia Carmona, Oriol, additional, Urrea, Victor, additional, de la Iglesia, Nuria, additional, Blanco-Heredia, Juan, additional, Anjos-Souza, Carla, additional, Varela, Ismael, additional, Trinité, Benjamin, additional, Tarrés-Freixas, Ferran, additional, Rovirosa, Carla, additional, Lepore, Rosalba, additional, Vazquez, Miguel, additional, de Mattos-Arruda, Leticia, additional, Valencia, Alfonso, additional, Clotet, Bonaventura, additional, Aguilar-Gurrieri, Carmen, additional, Guallar, Victor, additional, Carrillo, Jorge, additional, and Blanco, Julià, additional

Published
2023
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27. An HIV-1 Replication Pathway Utilizing Reverse Transcription Products That Fail To Integrate

Author

Trinité, Benjamin, Ohlson, Eric C, Voznesensky, Igor, Rana, Shashank P, Chan, Chi N, Mahajan, Saurabh, Alster, Jason, Burke, Sean A, Wodarz, Dominik, and Levy, David N

Subjects
Genetics, Infectious Diseases, HIV/AIDS, Aetiology, 2.1 Biological and endogenous factors, Infection, CD4-Positive T-Lymphocytes, DNA, Viral, Gene Expression Regulation, Viral, HIV Infections, HIV-1, Humans, Reverse Transcription, Viral Proteins, Virus Integration, Virus Replication, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology
Abstract

Integration is a central event in the replication of retroviruses, yet ≥ 90% of HIV-1 reverse transcripts fail to integrate, resulting in accumulation of unintegrated viral DNA in cells. However, understanding what role, if any, unintegrated viral DNA plays in the natural history of HIV-1 has remained elusive. Unintegrated HIV-1 DNA is reported to possess a limited capacity for gene expression restricted to early gene products and is considered a replicative dead end. Although the majority of peripheral blood CD4(+) T cells are refractory to infection, nonactivated CD4 T cells present in lymphoid and mucosal tissues are major targets for infection. Treatment with cytokine interleukin-2 (IL-2), IL-4, IL-7, or IL-15 renders CD4(+) T cells permissive to HIV-1 infection in the absence of cell activation and proliferation and provides a useful model for infection of resting CD4(+) T cells. We found that infection of cytokine-treated resting CD4(+) T cells in the presence of raltegravir or with integrase active-site mutant HIV-1 yielded de novo virus production following subsequent T cell activation. Infection with integration-competent HIV-1 naturally generated a population of cells generating virus from unintegrated DNA. Latent infection persisted for several weeks and could be activated to virus production by a combination of a histone deacetylase inhibitor and a protein kinase C activator or by T cell activation. HIV-1 Vpr was essential for unintegrated HIV-1 gene expression and de novo virus production in this system. Bypassing integration by this mechanism may allow the preservation of genetic information that otherwise would be lost.

Published
2013

28. Exploring FeLV-Gag-Based VLPs as a New Vaccine Platform—Analysis of Production and Immunogenicity

Author

Ortiz, Raquel, primary, Barajas, Ana, additional, Pons-Grífols, Anna, additional, Trinité, Benjamin, additional, Tarrés-Freixas, Ferran, additional, Rovirosa, Carla, additional, Urrea, Victor, additional, Barreiro, Antonio, additional, Gonzalez-Tendero, Anna, additional, Cardona, Maria, additional, Ferrer, Laura, additional, Clotet, Bonaventura, additional, Carrillo, Jorge, additional, Aguilar-Gurrieri, Carmen, additional, and Blanco, Julià, additional

Published
2023
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29. Immunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 and golden Syrian hamster upon SARS-CoV-2 infection.

Author

Carrillo, Jorge, primary, Ávila-Nieto, Carlos, additional, Vergara-Alert, Júlia, additional, Amengual-Rigo, Pep, additional, Ainsua-Enrich, Erola, additional, Brustolin, Marco, additional, Concepción, Maria Luisa Rodriguez de la, additional, Pedreño-Lopez, Nuria, additional, Rodon, Jordi, additional, Urrea, Victor, additional, Pradenas, Edwards, additional, Marfil, Silvia, additional, Ballana, Ester, additional, Riveira-Muñoz, Eva, additional, Pérez, Mónica, additional, Roca, Núria, additional, Tarrés-Freixas, Ferran, additional, Cantero, Guillermo, additional, Pons-Grífols, Anna, additional, Rovirosa, Carla, additional, Aguilar-Gurrieri, Carmen, additional, Ortiz, Raquel, additional, Barajas, Ana, additional, Trinité, Benjamin, additional, Lepore, Rosalba, additional, Muñoz-Basagoiti, Jordana, additional, Perez-Zsolt, Daniel, additional, Izquierdo-Useros, Nuria, additional, Valencia, Alfonso, additional, Blanco, Julià, additional, Guallar, Víctor, additional, Clotet, Bonaventura, additional, and Segalés, Joaquim, additional

Published
2023
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30. Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial

Author

Corominas, Júlia, primary, Garriga, Carme, additional, Prenafeta, Antoni, additional, Moros, Alexandra, additional, Cañete, Manuel, additional, Barreiro, Antonio, additional, González-González, Luis, additional, Madrenas, Laia, additional, Güell, Irina, additional, Clotet, Bonaventura, additional, Izquierdo-Useros, Nuria, additional, Raïch-Regué, Dàlia, additional, Gallemí, Marçal, additional, Blanco, Julià, additional, Pradenas, Edwards, additional, Trinité, Benjamin, additional, Prado, Julia G., additional, Blanch-Lombarte, Oscar, additional, Pérez-Caballero, Raúl, additional, Plana, Montserrat, additional, Esteban, Ignasi, additional, Pastor-Quiñones, Carmen, additional, Núñez-Costa, Xavier, additional, Taleb, Rachel Abu, additional, McSkimming, Paula, additional, Soriano, Alex, additional, Nava, Jocelyn, additional, Anagua, Jesse Omar, additional, Ramos, Rafel, additional, Lluch, Ruth Martí, additional, Comes, Aida Corpes, additional, Romero, Susana Otero, additional, Gomez, Xavier Martinez, additional, Sans-Pola, Carla, additional, Moltó, José, additional, Benet, Susana, additional, Bailón, Lucía, additional, Arribas, Jose R., additional, Borobia, Alberto M., additional, Parada, Javier Queiruga, additional, Navarro-Pérez, Jorge, additional, Forner Giner, Maria José, additional, Lucas, Rafael Ortí, additional, Jiménez, María del Mar Vázquez, additional, Compán, Salvador Oña, additional, Alvarez-Mon, Melchor, additional, Troncoso, Daniel, additional, Arana-Arri, Eunate, additional, Meijide, Susana, additional, Imaz-Ayo, Natale, additional, García, Patricia Muñoz, additional, de la Villa Martínez, Sofía, additional, Fernández, Sara Rodríguez, additional, Prat, Teresa, additional, Torroella, Èlia, additional, and Ferrer, Laura, additional

Published
2023
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31. Cyanovirin-N binds to select SARS-CoV-2 spike oligosaccharides outside of the receptor binding domain and blocks infection by SARS-CoV-2

Author

Muñoz-Basagoiti, Jordana, primary, Monteiro, Fábio Luís Lima, additional, Krumpe, Lauren R. H., additional, Armario-Najera, Victoria, additional, Shenoy, Shilpa R., additional, Perez-Zsolt, Daniel, additional, Westgarth, Harrison James, additional, Villorbina, Gemma, additional, Bomfim, Larissa Maciel, additional, Raïch-Regué, Dàlia, additional, Nogueras, Lara, additional, Henrich, Curtis J., additional, Gallemí, Marçal, additional, Moreira, Filipe Romero Rebello, additional, Torres, Pascual, additional, Wilson, Jennifer, additional, D’arc, Mirela, additional, Marfil, Silvia, additional, Herlinger, Alice Laschuk, additional, Pradenas, Edwards, additional, Higa, Luiza Mendonça, additional, Portero-Otin, Manuel, additional, Trinité, Benjamin, additional, Twyman, Richard M., additional, Capell, Teresa, additional, Tanuri, Amilcar, additional, Blanco, Julià, additional, Izquierdo-Useros, Nuria, additional, Rech, Elibio L., additional, Christou, Paul, additional, and O’Keefe, Barry R., additional

Published
2023
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33. A Novel Monoclonal Antibody Targeting a Large Surface of the Receptor Binding Motif Shows Pan-neutralizing SARS-CoV-2 Activity Including BQ.1.1 Variant

Author

de Campos-Mata, Leire, primary, Trinité, Benjamin, additional, Modrego, Andrea, additional, Vaquero, Sonia Tejedor, additional, Pradenas, Edwards, additional, Melero, Natalia Rodrigo, additional, Carlero, Diego, additional, Marfil, Silvia, additional, Pons-Grífols, Anna, additional, Bueno-Carrasco, María Teresa, additional, Santiago, César, additional, Tarrés-Freixas, Ferran, additional, Urrea, Victor, additional, Izquierdo, Nuria, additional, Riveira-Muñoz, Eva, additional, Ballana, Ester, additional, Pérez, Mónica, additional, Vergara-Alert, Júlia, additional, Segalés, Joaquim, additional, Carolis, Carlo, additional, Arranz, Rocío, additional, Blanco, Julià, additional, and Magri, Giuliana, additional

Published
2023
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34. Impact of chemotherapy and/or immunotherapy on neutralizing antibody response to SARS‐CoV ‐2 mRNA ‐1237 vaccine in patients with solid tumors

Author

Felip, Eudald, primary, Pradenas, Edwards, additional, Romeo, Margarita, additional, Marfil, Silvia, additional, Trinité, Benjamin, additional, Urrea, Víctor, additional, Hernández, Ainhoa, additional, Ballana, Ester, additional, Cucurull, Marc, additional, Mateu, Lourdes, additional, Massanella, Marta, additional, Clotet, Bonaventura, additional, Morán, Teresa, additional, and Blanco, Julià, additional

Published
2022
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35. Cyanovirin-N binds to select SARS-CoV-2 spike oligosaccharides outside of the receptor binding domain and blocks infection by SARS-CoV-2

Author

Muñoz-Basagoiti, Jordana, Monteiro, Fábio Luís Lima, Krumpe, Lauren R.H., Armario-Nájera, Victoria, Shenoy, Shilpa R., Perez-Zsolt, Daniel, Westgarth, Harrison James, Villorbina Noguera, Gemma, Bomfim, Larissa Maciel, Raïch-Regué, Dàlia, Nogueras Penabad, Lara, Henrich, Curtis J., Gallemí, Marçal, Moreira, Filipe Romero Rebello, Torres Cabestany, Pascual, Wilson, Jennifer, D’arc, Mirela, Marfil, Silvia, Herlinger, Alice Laschuk, Pradenas, Edwards, Higa, Luiza Mendonça, Portero Otín, Manuel, Trinité, Benjamin, Twyman, Richard M., Capell Capell, Teresa, Tanuri, Amilcar, Blanco, Julià, Izquierdo-Useros, Nuria, Rech, Elibio L., Christou, Paul, O’Keefec, Barry R., and Higa, Higa,Luiza Mendonça

Subjects
Multidisciplinary, Cyanovirin N, Antiviral, Lectin, Oligosacàrids
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped positive stranded RNA virus which has caused the recent deadly pandemic called COVID-19. The SARS-CoV-2 virion is coated with a heavily glycosylated Spike glycoprotein which is responsible for attachment and entry into target cells. One, as yet unexploited strategy for preventing SARS-CoV-2 infections, is the targeting of the glycans on Spike. Lectins are carbohydrate-binding proteins produced by plants, algae, and cyanobacteria. Some lectins can neutralize enveloped viruses displaying external glycoproteins, offering an alternative therapeutic approach for the prevention of infection with virulent β-coronaviruses, such as SARS-CoV-2. Here we show that the cyanobacterial lectin cyanovirin-N (CV-N) can selectively target SARS-CoV-2 Spike oligosaccharides and inhibit SARS-CoV-2 infection in vitro and in vivo. CV-N neutralizes Delta and Omicron variants in vitro better than earlier circulating viral variants. CV-N binds selectively to Spike with a Kd as low as 15 nM and a stoichiometry of 2 CV-N: 1 Spike but does not bind to the receptor binding domain (RBD). Further mapping of CV-N binding sites on Spike shows that select high-mannose oligosaccharides in the S1 domain of Spike are targeted by CV-N. CV-N also reduced viral loads in the nares and lungs in vivo to protect hamsters against a lethal viral challenge. In summary, we present an anti-coronavirus agent that works by an unexploited mechanism and prevents infection by a broad range of SARS-CoV-2 strains. Agricultural Biotechnology and Bioeconomy Unit (ABBU), Universitat de Lleida, Spain, EU Pharma-Factory grant agreement 77,4078 to P.C. Research in NI-U’s lab is supported by the Spanish Ministry of Science and Innovation (grant PID2020-117145RB-I00),EU HORIZON-HLTH-2021-CORONA-01 (grant 101046118) and by institutional funding of Grifols,Pharma Mar,HIPRA,Amassence,and Palobiofarma. E.L.R. is supported by Embrapa Genetic Resources and Biotechnology/National Institute of Science and Technology in Synthetic Biology, National Council for Scientific and Technological Development (465603/2014-9), Research Support Foundation of the Federal District (0193.001.262/2017), and Coordination for the Improvement of Higher Education Personnel. This research has been supported in part by the Intramural Research Program of the NIH, NCI, Center for Cancer Research and with federal funds from the NCI, NIH, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S.Government.All animal experiments were approved by

Published
2023

37. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and humoral responses against different variants of concern in domestic pet animals and stray cats from North‐Eastern Spain

Author

Fernández‐Bastit, Leira, primary, Marfil, Silvia, additional, Pradenas, Edwards, additional, Valle, Rosa, additional, Roca, Núria, additional, Rodon, Jordi, additional, Pailler‐García, Lola, additional, Trinité, Benjamin, additional, Parera, Mariona, additional, Noguera‐Julian, Marc, additional, Martorell, Jaume, additional, Izquierdo‐Useros, Nuria, additional, Carrillo, Jorge, additional, Clotet, Bonaventura, additional, Blanco, Julià, additional, Vergara‐Alert, Júlia, additional, and Segalés, Joaquim, additional

Published
2022
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38. Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients

Author

Rokx, Casper, Lammers, Jolanda, Buitenhuis, Lonneke, Postma, Douwe, Koster, David, Lukens, Michaèl, Scholtens, Thea, Boomgaard, Maartje van den, Kampschreur, Linda, Ubals, Maria, Prat, Núria, Díez Sánchez, Beatriz, Vértiz Guidotti, Thatiana, Pons Barber, Maria, Gonzalez Ruiz, Cristian, Navarrete Gonzalez, Laura, Ancochea, Àgueda, Ferrer, Magí, Videla, Sebas, Gudiol, Carlota, Fernández Rivas, Gema, CoV-Early Study Group, Vonderen, Marit van, Bianco, Andrea Sofia, Bravo, Anna, Otero, Aurema, Ruibal Suarez, Jose Carlos, Benavent, Sergio, Zarauza Pellejero, Alvaro, Línio, Rosa, Malchair, Pierre, Llopis Roca, Ferran, Blanco, Julian, Rodriguez Cortez, Orlando, Casares Gonzalez, Pablo, Arcos Vila, Gemma, García, Yolanda, Roca Font, Judit, Carrasco Matos, Katherine M., Saüch Valmaña, Glòria, Vidal Obradors, Carla, Koopmans, Marion, Ara, Jordi, COnV-ert Study Group, Rodríguez Codina, Joana, Tarres García, Silvia, Blanco, Ignacio, Hernández, Águeda, González Soler, Victoria, Curriu Sabatès, Margarida, Nieto Rodríguez, Raquel, Grífols, Joan Ramon, Briones Zambrano, Ney Nicanor, Millan, Anna, Capdevila Jáuregui, Mar, Fornos, Miriam, Casamitjana, Natàlia, Bordoy, Antoni E., Alonso, Eva, Zwet, Erik van, Miedema, Jelle, Martinez, Núria, Ramírez Morros, Anna, Bogers, Susanne, Maglio, Laura Analía, Amado Simon, Rosa, Comellas Fernandez, Laura, Garcia, Nadia, Ruiz Comellas, Anna, Baro, Bàrbara, Hernández, Luis, Viozquez Meya, Maria, Costes, Gèlia, Pradenas, Edwars, Forcada, Anna, Ginneken, Betty van, Harvala, Heli, Marfil, Silvia, Troxel, Andrea, Mooijaart, Simon, Trinité, Benjamin, Piccolo Ferreira, Francini, Bonet, Mireia, Cantoni, Jordi, Russcher, Henk, Marks, Michael, Zwaginga, Jaap Jan, Torrano Soler, Pamela, Mitjà, Oriol, Rijnders, Bart J. A., Droog, José de, Corbacho Monné, Marc, Scherpenisse, Cees, Hollander, Jan den, Gharbharan, Arvind, Jordans, Carlijn, Geurtsvankessel, Corine, Albersen, Arjan, Papageourgiou, Grigorios, Katsikis, Peter, Vall Mayans, Martí, Müller, Yvonne, Reusken, Chantal, San José, Alba, Ferrer, Susana, Engen, Rene van, Karisli, Ayten, Götz, Hannelore, Struik, Jelle, París, Alexa, Suñer Navarro, Clara, Clotet, Bonaventura, 1953, Reimerink, Johan, Rokx-Niemantsverdriet, Lotte, Rodriguez Arias, Miquel Angel, Jiménez, Zahida, Verstijnen, Jose, Geloven, Nan van, Groeneveld, Geert, Zwaginga, Lisa, Oud, Josine, Meier, Romy, González Beiras, Camila, Swaneveld, Francis, Ramírez Viaplana, Ferran, Schoot, Ellen van der, Vrielink, Hans, Flores Aguilera, Begoña, Vivero Larraza, Ainhoa, Watering, Leo van de, Hogema, Boris, González García, David, Wijngaarden, Peter van, Vidal Alaball, Josep, Etten, Ronald van, Gammeren, Adriaan van, Alemany, Andrea, Puig, Jordi, Maas, Nanda, Berg – Rahman, Juliette van der, Karim, Faiz, Hiddema, Siepke, Elst, Kim van, García García, Vanesa, Casañ Lopez, Cristina, Leeuwen-Segarceanu, Elena van, Nieto, Aroa, Rodríguez Sevilla, Graciela, Reitsma, Annette, Molenkamp, Karin, Soetekouw, Robert, Band, Caterina, Carceles Peiró, Victor, Gallardo, Mireia, Galvan Femenia, Ivan, Comas Leon, Xavier, Millat Martínez, Pere, Bassat Orellana, Quique, González, María Isabel, Verdaguer, Joaquim, Roquer López, Clàudia, Contreras, Enric, Giménez, Montserrat, Ouchi, Dan, Blanco Guillermo, Ignacio, Bonet Papell, Glòria, Dastis Arias, Macarena, Delgado Capel, Maria, Faculteit Medische Wetenschappen/UMCG, Internal Medicine, Medical Microbiology & Infectious Diseases, Virology, and Epidemiology

Subjects
Immunoregulació, Multidisciplinary, SARS-CoV-2, Immunization, Passive, Immunoregulation, COVID-19, General Physics and Astronomy, Bayes Theorem, General Chemistry, Middle Aged, General Biochemistry, Genetics and Molecular Biology, Treatment Outcome, Outpatients, Humans, Multicenter Studies as Topic, COVID-19 Serotherapy, Randomized Controlled Trials as Topic
Abstract

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when Trial registration: Clinicaltrials.gov NCT04621123 and NCT04589949. Registration: NCT04621123 and NCT04589949 on https://www.clinicaltrials.gov

Published
2022

39. Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial

Author

Corominas, Júlia, primary, Garriga, Carme, additional, Prenafeta, Antoni, additional, Moros, Alexandra, additional, Cañete, Manuel, additional, Barreiro, Antonio, additional, González-González, Luis, additional, Madrenas, Laia, additional, Güell, Irina, additional, Clotet, Bonaventura, additional, Izquierdo-Useros, Nuria, additional, Raïch-Regué, Dàlia, additional, Gallemí, Marçal, additional, Blanco, Julià, additional, Pradenas, Edwards, additional, Trinité, Benjamin, additional, Prado, Julia G, additional, Blanch-Lombarte, Oscar, additional, Pérez-Caballero, Raúl, additional, Plana, Montserrat, additional, Esteban, Ignasi, additional, Pastor-Quiñones, Carmen, additional, Núñez-Costa, Xavier, additional, Taleb, Rachel Abu, additional, McSkimming, Paula, additional, Soriano, Alex, additional, Nava, Jocelyn, additional, Anagua, Jesse Omar, additional, Ramos, Rafel, additional, Lluch, Ruth Martí, additional, Comes, Aida Corpes, additional, Romero, Susana Otero, additional, Gomez, Xavier Martinez, additional, Sans-Pola, Carla, additional, Moltó, José, additional, Benet, Susana, additional, Bailón, Lucía, additional, Arribas, Jose R, additional, Borobia, Alberto M, additional, Parada, Javier Queiruga, additional, Navarro-Pérez, Jorge, additional, Forner Giner, Maria José, additional, Lucas, Rafael Ortí, additional, Vázquez Jiménez, María del Mar, additional, Compán, Salvador Oña, additional, Alvarez-Mon, Melchor, additional, Troncoso, Daniel, additional, Arana-Arri, Eunate, additional, Meijide, Susana, additional, Imaz-Ayo, Natale, additional, García, Patricia Muñoz, additional, de la Villa Martínez, Sofía, additional, Fernández, Sara Rodríguez, additional, Prat, Teresa, additional, Torroella, Èlia, additional, and Ferrer, Laura, additional

Published
2022
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40. Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice

Author

Tarrés-Freixas, Ferran, primary, Trinité, Benjamin, additional, Pons-Grífols, Anna, additional, Romero-Durana, Miguel, additional, Riveira-Muñoz, Eva, additional, Ávila-Nieto, Carlos, additional, Pérez, Mónica, additional, Garcia-Vidal, Edurne, additional, Perez-Zsolt, Daniel, additional, Muñoz-Basagoiti, Jordana, additional, Raïch-Regué, Dàlia, additional, Izquierdo-Useros, Nuria, additional, Andrés, Cristina, additional, Antón, Andrés, additional, Pumarola, Tomàs, additional, Blanco, Ignacio, additional, Noguera-Julián, Marc, additional, Guallar, Victor, additional, Lepore, Rosalba, additional, Valencia, Alfonso, additional, Urrea, Victor, additional, Vergara-Alert, Júlia, additional, Clotet, Bonaventura, additional, Ballana, Ester, additional, Carrillo, Jorge, additional, Segalés, Joaquim, additional, and Blanco, Julià, additional

Published
2022
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41. Evaluation of SARS-CoV-2 entry, inflammation and new therapeutics in human lung tissue cells

Author

Grau-Expósito, Judith, Perea, David, Suppi, Marina, Massana, Núria, Vergara, Ander, Soler, Maria José, Trinité, Benjamin, Blanco, Julià, García-Pérez, Javier, Alcamí, José, Serrano-Mollar, Anna, Rosado Rodríguez, Joel, Falcó, Vicenç, Genescà Ferrer, Meritxell, Buzón, Maria José, Universitat Autònoma de Barcelona, Grau-Expósito, Judith, Perea, David, Suppi, Marina, Massana, Núria, Vergara, Ander, Soler, Maria José, Trinité, Benjamin, Blanco, Julià, García-Pérez, Javier, Alcamí, José, Serrano-Mollar, Anna, Rosado Rodríguez, Joel, Falcó, Vicenç, Genescà Ferrer, Meritxell, Buzón, Maria José, and Universitat Autònoma de Barcelona

Abstract

The development of physiological models that reproduce SARS-CoV-2 infection in primary human cells will be instrumental to identify host-pathogen interactions and potential therapeutics. Here, using cell suspensions directly from primary human lung tissues (HLT), we have developed a rapid platform for the identification of viral targets and the expression of viral entry factors, as well as for the screening of viral entry inhibitors and anti-inflammatory compounds. The direct use of HLT cells, without long-term cell culture and in vitro differentiation approaches, preserves main immune and structural cell populations, including the most susceptible cell targets for SARS-CoV-2; alveolar type II (AT-II) cells, while maintaining the expression of proteins involved in viral infection, such as ACE2, TMPRSS2, CD147 and AXL. Further, antiviral testing of 39 drug candidates reveals a highly reproducible method, suitable for different SARS-CoV-2 variants, and provides the identification of new compounds missed by conventional systems, such as VeroE6. Using this method, we also show that interferons do not modulate ACE2 expression, and that stimulation of local inflammatory responses can be modulated by different compounds with antiviral activity. Overall, we present a relevant and rapid method for the study of SARS-CoV-2. The early stages of laboratory identification of therapeutics against pathogens is usually based on the use of immortalized cell lines, as exemplified by many studies screening antivirals against SARS-CoV-2. Cell lines are manipulated for their continuous growth which offers several advantages, however they do not fully reproduce the behavior of primary cells nor the complexity of heterogeneous populations. In this study, we overcome this limitation by using surgical resections to establish human lung tissue (HLT) cell cultures ready for drug evaluation. First, we show that HLT preserves lung cell composition, including the main SARS-CoV-2 cellular target

Published
2022

42. Clinical course impacts early kinetics,magnitude, and amplitude of SARS-CoV-2 neutralizing antibodies beyond 1 year after infection

Author

Barcelona Supercomputing Center, Pradenas, Edwards, Trinité, Benjamin, Urrea, Víctor, Marfil, Silvia, Tarrés Freixas, Ferran, Guallar, Victor, Valencia, Alfonso, Barcelona Supercomputing Center, Pradenas, Edwards, Trinité, Benjamin, Urrea, Víctor, Marfil, Silvia, Tarrés Freixas, Ferran, Guallar, Victor, and Valencia, Alfonso

Abstract

To understand the determinants of long-term immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the concurrent impact of vaccination and emerging variants, we follow a prospective cohort of 332 patients with coronavirus disease 2019 (COVID-19) over more than a year after symptom onset. We evaluate plasma-neutralizing activity using HIV-based pseudoviruses expressing the spike of different SARS-CoV-2 variants and analyze them longitudinally using mixed-effects models. Long-term neutralizing activity is stable beyond 1 year after infection in mild/asymptomatic and hospitalized participants. However, longitudinal models suggest that hospitalized individuals generate both short- and long-lived memory B cells, while the responses of non-hospitalized individuals are dominated by long-lived B cells. In both groups, vaccination boosts responses to natural infection. Long-term (>300 days from infection) responses in unvaccinated participants show a reduced efficacy against beta, but not alpha nor delta, variants. Multivariate analysis identifies the severity of primary infection as an independent determinant of higher magnitude and lower relative cross-neutralization activity of long-term neutralizing responses., This work was partially funded by Grifols, the Departament de Salut of the Generalitat de Catalunya (grants SLD016 to J.B. and SLD015 to J.C.), the Spanish Health Institute Carlos III and the European Regional Development Fund (grant PI17/01518 and PI20/00093 to J.B. and PI18/01332 to J.C.), CERCA Programme/Generalitat de Catalunya 2017 SGR 252, and the crowdfunding initiatives #joemcorono, BonPreu/Esclat, and Correos. The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript. E.P. was supported by a doctoral grant from the National Agency for Research and Development of Chile (ANID) (72180406). We are grateful to all participants and the technical staff of IrsiCaixa for sample processing. Francesc López-Seguí provided medical writing support during the preparation of the manuscript., Peer Reviewed, "Article signat per 22 autors/es: Edwards Pradenas, Benjamin Trinité, Víctor Urrea, Silvia Marfil, Ferran Tarrés-Freixas, Raquel Ortiz, Carla Rovirosa, Jordi Rodon, Júlia Vergara-Alert, Joaquim Segalés, Victor Guallar, Alfonso Valencia, Nuria Izquierdo-Useros, Marc Noguera-Julian, Jorge Carrillo, Roger Paredes, Lourdes Mateu, Anna Chamorro, Ruth Toledo, Marta Massanella, Bonaventura Clotet, Julià Blanco", Postprint (published version)

Published
2022

43. EC50 and CC50 of 39 antiviral drug candidates

Author

Grau-Expósito, Judith, Perea, David, Suppi, Marina, Massana, Nuria, Vergara, Ander, Soler, María José, Trinité, Benjamin, Blanco, Julià, García-Pérez, Javier, Alcamí, José, Serrano-Mollar, Anna, Rosado, Joel, Falcó, Vicenç, Genesca, Meritxell, Buzón, María José, Grau-Expósito, Judith, Perea, David, Suppi, Marina, Massana, Nuria, Vergara, Ander, Soler, María José, Trinité, Benjamin, Blanco, Julià, García-Pérez, Javier, Alcamí, José, Serrano-Mollar, Anna, Rosado, Joel, Falcó, Vicenç, Genesca, Meritxell, and Buzón, María José

Published
2022

44. Gating strategy for the identification of cell subpopulations in the human lung tissue model

Author

Grau-Expósito, Judith, Perea, David, Suppi, Marina, Massana, Nuria, Vergara, Ander, Soler, María José, Trinité, Benjamin, Blanco, Julià, García-Pérez, Javier, Alcamí, José, Serrano-Mollar, Anna, Rosado, Joel, Falcó, Vicenç, Genesca, Meritxell, Buzón, María José, Grau-Expósito, Judith, Perea, David, Suppi, Marina, Massana, Nuria, Vergara, Ander, Soler, María José, Trinité, Benjamin, Blanco, Julià, García-Pérez, Javier, Alcamí, José, Serrano-Mollar, Anna, Rosado, Joel, Falcó, Vicenç, Genesca, Meritxell, and Buzón, María José

Published
2022

45. S4 Fig - Evaluation of SARS-CoV-2 entry, inflammation and new therapeutics in human lung tissue cells

Author

Grau-Expósito, Judith, Perea, David, Suppi, Marina, Massana, Nuria, Vergara, Ander, Soler, María José, Trinité, Benjamin, Blanco, Julià, García-Pérez, Javier, Alcamí, José, Serrano-Mollar, Anna, Rosado, Joel, Falcó, Vicenç, Genesca, Meritxell, Buzón, María José, Grau-Expósito, Judith, Perea, David, Suppi, Marina, Massana, Nuria, Vergara, Ander, Soler, María José, Trinité, Benjamin, Blanco, Julià, García-Pérez, Javier, Alcamí, José, Serrano-Mollar, Anna, Rosado, Joel, Falcó, Vicenç, Genesca, Meritxell, and Buzón, María José

Published
2022

46. Antiviral drug candidates for entry inhibition of SARS-CoV-2

Author

Grau-Expósito, Judith, Perea, David, Suppi, Marina, Massana, Nuria, Vergara, Ander, Soler, María José, Trinité, Benjamin, Blanco, Julià, García-Pérez, Javier, Alcamí, José, Serrano-Mollar, Anna, Rosado, Joel, Falcó, Vicenç, Genesca, Meritxell, Buzón, María José, Grau-Expósito, Judith, Perea, David, Suppi, Marina, Massana, Nuria, Vergara, Ander, Soler, María José, Trinité, Benjamin, Blanco, Julià, García-Pérez, Javier, Alcamí, José, Serrano-Mollar, Anna, Rosado, Joel, Falcó, Vicenç, Genesca, Meritxell, and Buzón, María José

Published
2022

47. Gating strategy for the identification of anti-inflammatory effects of selected compounds

Author

Grau-Expósito, Judith, Perea, David, Suppi, Marina, Massana, Nuria, Vergara, Ander, Soler, María José, Trinité, Benjamin, Blanco, Julià, García-Pérez, Javier, Alcamí, José, Serrano-Mollar, Anna, Rosado, Joel, Falcó, Vicenç, Genesca, Meritxell, Buzón, María José, Grau-Expósito, Judith, Perea, David, Suppi, Marina, Massana, Nuria, Vergara, Ander, Soler, María José, Trinité, Benjamin, Blanco, Julià, García-Pérez, Javier, Alcamí, José, Serrano-Mollar, Anna, Rosado, Joel, Falcó, Vicenç, Genesca, Meritxell, and Buzón, María José

Published
2022

48. Optimization of lung tissue enzymatic digestion visualized by t-distributed Stochastic Neighbor Embedding (tSNE), and representative SPC and ACE2 expression

Author

Grau-Expósito, Judith, Perea, David, Suppi, Marina, Massana, Nuria, Vergara, Ander, Soler, María José, Trinité, Benjamin, Blanco, Julià, García-Pérez, Javier, Alcamí, José, Serrano-Mollar, Anna, Rosado, Joel, Falcó, Vicenç, Genesca, Meritxell, Buzón, María José, Grau-Expósito, Judith, Perea, David, Suppi, Marina, Massana, Nuria, Vergara, Ander, Soler, María José, Trinité, Benjamin, Blanco, Julià, García-Pérez, Javier, Alcamí, José, Serrano-Mollar, Anna, Rosado, Joel, Falcó, Vicenç, Genesca, Meritxell, and Buzón, María José

Published
2022

49. Visual summary of the HLT model

Author

Grau-Expósito, Judith, Perea, David, Suppi, Marina, Massana, Nuria, Vergara, Ander, Soler, María José, Trinité, Benjamin, Blanco, Julià, García-Pérez, Javier, Alcamí, José, Serrano-Mollar, Anna, Rosado, Joel, Falcó, Vicenç, Genesca, Meritxell, Buzón, María José, Grau-Expósito, Judith, Perea, David, Suppi, Marina, Massana, Nuria, Vergara, Ander, Soler, María José, Trinité, Benjamin, Blanco, Julià, García-Pérez, Javier, Alcamí, José, Serrano-Mollar, Anna, Rosado, Joel, Falcó, Vicenç, Genesca, Meritxell, and Buzón, María José

Abstract

Ex vivo physiological systems for the study of SARS-CoV-2-host interactions are scarce. We establish a method using primary human lung tissue (HLT) cells for the rapid analysis of cell tropism and identification of therapeutics. Main findings: i) HLT cells preserve main cell subpopulations, including alveolar type-II cells, and expression of SARS-CoV-2 entry factors ACE2, CD147, TMPRSS2 and AXL. ii) HLT cells are readily susceptible to SARS-CoV-2 infection without the need of cell isolation or further cell differentiation. iii) Antiviral testing in HLT cells allows the rapid identification of new drug candidates against SARS-CoV-2 variants, missed by conventional systems. iv) Local inflammation is supported in HLT cells and offers the identification of relevant anti-inflammatory compounds for SARS-CoV-2 infection.

Published
2022

50. Evaluation of SARS-CoV-2 entry, inflammation and new therapeutics in human lung tissue cells

Author

Generalitat de Catalunya, Instituto de Salud Carlos III, European Commission, Fundació La Marató de TV3, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Gilead Sciences, Taller Argal, Vall d'Hebron Research Institute, Grau-Expósito, Judith, Perea, David, Suppi, Marina, Massana, Nuria, Vergara, Ander, Soler, María José, Trinité, Benjamin, Blanco, Julià, García-Pérez, Javier, Alcamí, José, Serrano-Mollar, Anna, Rosado, Joel, Falcó, Vicenç, Genesca, Meritxell, Buzón, María José, Generalitat de Catalunya, Instituto de Salud Carlos III, European Commission, Fundació La Marató de TV3, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Gilead Sciences, Taller Argal, Vall d'Hebron Research Institute, Grau-Expósito, Judith, Perea, David, Suppi, Marina, Massana, Nuria, Vergara, Ander, Soler, María José, Trinité, Benjamin, Blanco, Julià, García-Pérez, Javier, Alcamí, José, Serrano-Mollar, Anna, Rosado, Joel, Falcó, Vicenç, Genesca, Meritxell, and Buzón, María José

Abstract

The development of physiological models that reproduce SARS-CoV-2 infection in primary human cells will be instrumental to identify host-pathogen interactions and potential therapeutics. Here, using cell suspensions directly from primary human lung tissues (HLT), we have developed a rapid platform for the identification of viral targets and the expression of viral entry factors, as well as for the screening of viral entry inhibitors and anti-inflammatory compounds. The direct use of HLT cells, without long-term cell culture and in vitro differentiation approaches, preserves main immune and structural cell populations, including the most susceptible cell targets for SARS-CoV-2; alveolar type II (AT-II) cells, while maintaining the expression of proteins involved in viral infection, such as ACE2, TMPRSS2, CD147 and AXL. Further, antiviral testing of 39 drug candidates reveals a highly reproducible method, suitable for different SARS-CoV-2 variants, and provides the identification of new compounds missed by conventional systems, such as VeroE6. Using this method, we also show that interferons do not modulate ACE2 expression, and that stimulation of local inflammatory responses can be modulated by different compounds with antiviral activity. Overall, we present a relevant and rapid method for the study of SARS-CoV-2.

Published
2022

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