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

المصدر: Nature Communications, Vol 15, Iss 1, Pp 1-18 (2024)

مصطلحات موضوعية: Science

الوصف: Abstract Safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are crucial to fight against the coronavirus disease 2019 pandemic. Most vaccines are based on a mutated version of the Spike glycoprotein [K986P/V987P (S-2P)] with improved stability, yield and immunogenicity. However, S-2P is still produced at low levels. Here, we describe the V987H mutation that increases by two-fold the production of the recombinant Spike and the exposure of the receptor binding domain (RBD). S-V987H immunogenicity is similar to S-2P in mice and golden Syrian hamsters (GSH), and superior to a monomeric RBD. S-V987H immunization confer full protection against severe disease in K18-hACE2 mice and GSH upon SARS-CoV-2 challenge (D614G or B.1.351 variants). Furthermore, S-V987H immunized K18-hACE2 mice show a faster tissue viral clearance than RBD- or S-2P-vaccinated animals challenged with D614G, B.1.351 or Omicron BQ1.1 variants. Thus, S-V987H protein might be considered for future SARS-CoV-2 vaccines development.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/417894952ca54f88947455ec8d336df7Test

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

المصدر: npj Vaccines, Vol 9, Iss 1, Pp 1-12 (2024)

مصطلحات موضوعية: Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Age is associated with reduced efficacy of vaccines and linked to higher risk of severe COVID-19. Here we determined the impact of ageing on the efficacy of a SARS-CoV-2 vaccine based on a stabilised Spike glycoprotein (S-29) that had previously shown high efficacy in young animals. Thirteen to 18-month-old golden Syrian hamsters (GSH) and 22–23-month-old K18-hCAE2 mice were immunised twice with S-29 protein in AddaVaxTM adjuvant. GSH were intranasally inoculated with SARS-CoV-2 either two weeks or four months after the booster dose, while all K18-hACE2 mice were intranasally inoculated two weeks after the second immunisation. Body weight and clinical signs were recorded daily post-inoculation. Lesions and viral load were investigated in different target tissues. Immunisation induced seroconversion and production of neutralising antibodies; however, animals were only partially protected from weight loss. We observed a significant reduction in the amount of viral RNA and a faster viral protein clearance in the tissues of immunized animals. Infectious particles showed a faster decay in vaccinated animals while tissue lesion development was not altered. In GSH, the shortest interval between immunisation and inoculation reduced RNA levels in the lungs, while the longest interval was equally effective in reducing RNA in nasal turbinates; viral nucleoprotein amount decreased in both tissues. In mice, immunisation was able to improve the survival of infected animals. Despite the high protection shown in young animals, S-29 efficacy was reduced in the geriatric population. Our research highlights the importance of testing vaccine efficacy in older animals as part of preclinical vaccine evaluation.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2059-0105Test

الوصول الحر: https://doaj.org/article/f305a783ac09456b913d3b908a30b8e8Test

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

المصدر: Nature Communications, Vol 15, Iss 1, Pp 1-13 (2024)

مصطلحات موضوعية: Science

الوصف: Abstract Here we report the characterization of 17T2, a SARS-CoV-2 pan-neutralizing human monoclonal antibody isolated from a COVID-19 convalescent individual infected during the first pandemic wave. 17T2 is a class 1 VH1-58/κ3-20 antibody, derived from a receptor binding domain (RBD)-specific IgA+ memory B cell, with a broad neutralizing activity against former and new SARS-CoV-2 variants, including XBB.1.16 and BA.2.86 Omicron subvariants. Consistently, 17T2 demonstrates in vivo prophylactic and therapeutic activity against Omicron BA.1.1 infection in K18-hACE2 mice. Cryo-electron microscopy reconstruction shows that 17T2 binds the BA.1 spike with the RBD in “up” position and blocks the receptor binding motif, as other structurally similar antibodies do, including S2E12. Yet, unlike S2E12, 17T2 retains its neutralizing activity against all variants tested, probably due to a larger RBD contact area. These results highlight the impact of small structural antibody changes on neutralizing performance and identify 17T2 as a potential candidate for future clinical interventions.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/e88c94774f434c16bec8caaf30b4258fTest

المؤلفون: Edurne Garcia-Vidal, Ignasi Calba, Eva Riveira-Muñoz, Elisabet García, Bonaventura Clotet, Pere Serra-Mitjà, Cecilia Cabrera, Ester Ballana, Roger Badia

المصدر: International Journal of Molecular Sciences, Vol 25, Iss 10, p 5318 (2024)

مصطلحات موضوعية: NOD-like receptor, innate immunity, respiratory mucosa, viral respiratory infections, SARS-CoV-2, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: The lung is prone to infections from respiratory viruses such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). A challenge in combating these infections is the difficulty in targeting antiviral activity directly at the lung mucosal tract. Boosting the capability of the respiratory mucosa to trigger a potent immune response at the onset of infection could serve as a potential strategy for managing respiratory infections. This study focused on screening immunomodulators to enhance innate immune response in lung epithelial and immune cell models. Through testing various subfamilies and pathways of pattern recognition receptors (PRRs), the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family was found to selectively activate innate immunity in lung epithelial cells. Activation of NOD1 and dual NOD1/2 by the agonists TriDAP and M-TriDAP, respectively, increased the number of IL-8+ cells by engaging the NF-κB and interferon response pathways. Lung epithelial cells showed a stronger response to NOD1 and dual NOD1/2 agonists compared to control. Interestingly, a less-pronounced response to NOD1 agonists was noted in PBMCs, indicating a tissue-specific effect of NOD1 in lung epithelial cells without inducing widespread systemic activation. The specificity of the NOD agonist pathway was confirmed through gene silencing of NOD1 (siRNA) and selective NOD1 and dual NOD1/2 inhibitors in lung epithelial cells. Ultimately, activation induced by NOD1 and dual NOD1/2 agonists created an antiviral environment that hindered SARS-CoV-2 replication in vitro in lung epithelial cells.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/25/10/5318Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/854ce5bee9f54421805d0baf4169e23eTest

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

المصدر: Frontiers in Immunology, Vol 14 (2023)

مصطلحات موضوعية: COVID-19, SARS-CoV-2, vaccine, neutralizing antibodies, humoral response, Spike glycoprotein, Immunologic diseases. Allergy, RC581-607

الوصف: Most COVID-19 vaccines are based on the SARS-CoV-2 Spike glycoprotein (S) or their subunits. However, S shows some structural instability that limits its immunogenicity and production, hampering the development of recombinant S-based vaccines. The introduction of the K986P and V987P (S-2P) mutations increases the production and immunogenicity of the recombinant S trimer, suggesting that these two parameters are related. Nevertheless, S-2P still shows some molecular instability and it is produced with low yield. Here we described a novel set of mutations identified by molecular modeling and located in the S2 region of the S-2P that increase its production up to five-fold. Besides their immunogenicity, the efficacy of two representative S-2P-based mutants, S-29 and S-21, protecting from a heterologous SARS-CoV-2 Beta variant challenge was assayed in K18-hACE2 mice (an animal model of severe SARS-CoV-2 disease) and golden Syrian hamsters (GSH) (a moderate disease model). S-21 induced higher level of WH1 and Delta variants neutralizing antibodies than S-2P in K18-hACE2 mice three days after challenge. Viral load in nasal turbinate and oropharyngeal samples were reduced in S-21 and S-29 vaccinated mice. Despite that, only the S-29 protein protected 100% of K18-hACE2 mice from severe disease. When GSH were analyzed, all immunized animals were protected from disease development irrespectively of the immunogen they received. Therefore, the higher yield of S-29, as well as its improved immunogenicity and efficacy protecting from the highly pathogenic SARS-CoV-2 Beta variant, pinpoint the S-29 mutant as an alternative to the S-2P protein for future SARS-CoV-2 vaccine development.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1291972/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/8d145e1f4f964517b358c973214ef36fTest

المؤلفون: Lucía Gutiérrez-Chamorro, Eudald Felip, Adrià Bernat-Peguera, Ifeanyi Jude Ezeonwumelu, Iris Teruel, Anna Martínez-Cardús, Bonaventura Clotet, Eva Riveira-Muñoz, Margarita Romeo, Mireia Margelí, Ester Ballana

المصدر: Frontiers in Immunology, Vol 14 (2023)

مصطلحات موضوعية: SAMHD1, ovarian cancer, RLR (RIG-I like receptors), interferon, inflammation, Immunologic diseases. Allergy, RC581-607

الوصف: PurposeSAMHD1 is a deoxynucleotide triphosphate (dNTP) triphosphohydrolase which has been proposed as a putative prognostic factor in haematological cancers and certain solid tumours, although with controversial data. Here, we evaluate SAMHD1 function in ovarian cancer, both in vitro and in ovarian cancer patients.MethodsSAMHD1 expression was downregulated in ovarian cancer cell lines OVCAR3 and SKOV3 by RNA interference. Gene and protein expression changes in immune signalling pathways were assessed. SAMHD1 expression in ovarian cancer patients was evaluated by immunohistochemistry and survival analysis was performed according to SAMHD1 expression.ResultsSAMHD1 knockdown induced a significant upregulation of proinflammatory cytokines concomitant to increased expression of the main RNA-sensors, MDA5 and RIG-I, and interferon-stimulated genes, supporting the idea that the absence of SAMHD1 promotes innate immune activation in vitro. To assess the contribution of SAMHD1 in ovarian cancer patients, tumours were stratified in SAMHD1-low and SAMHD1-high expressing tumours, resulting in significantly shorter progression free survival (PFS) and overall survival (OS) in SAMHD1-high expression subgroup (p=0.01 and 0.04, respectively).ConclusionsSAMHD1 depletion correlates with increased innate immune cell signalling in ovarian cancer cells. In clinical samples, SAMHD1-low expressing tumors showed increased progression free survival and overall survival irrespective of BRCA mutation status. These results point towards SAMHD1 modulation as a new therapeutic strategy, able to enhance innate immune activation directly in tumour cells, leading to improved prognosis in ovarian cancer.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1112761/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/d2aa10bcd48743669aaac70f4a0f8900Test

المؤلفون: Eva Riveira-Muñoz, Edurne Garcia-Vidal, Manuel Bañó-Polo, Rubén León, Vanessa Blanc, Bonaventura Clotet, Ester Ballana

المصدر: Viruses, Vol 15, Iss 7, p 1433 (2023)

مصطلحات موضوعية: HSV, HPV, CPC, oral infection, enveloped viruses, Microbiology, QR1-502

الوصف: The oral cavity is particularly susceptible to viral infections that are self-recovering in most cases. However, complications may appear in severe cases and/or immunocompromised subjects. Cetylpyridinium chloride (CPC)-containing mouthwashes are able to decrease the infectivity of the SARS-CoV-2 virus by disrupting the integrity of the viral envelope. Here, we show that CPC, as the active ingredient contained in commercialized, exerts significant antiviral activity against enveloped viruses, such as HSV-1, but not against non-enveloped viruses, such as HPV. CPC-containing mouthwashes have been used as antiseptics for decades, and thus, they can represent a cost-effective measure to limit infection and spread of enveloped viruses infecting the oral cavity, aiding in reducing viral transmission.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1999-4915/15/7/1433Test; https://doaj.org/toc/1999-4915Test

الوصول الحر: https://doaj.org/article/369548407c944a0b83b348f0014a3819Test

المؤلفون: Ifeanyi Jude Ezeonwumelu, Edurne García-Vidal, Eudald Felip, Maria C. Puertas, Bruna Oriol-Tordera, Lucía Gutiérrez-Chamorro, André Gohr, Marta Ruiz-Riol, Marta Massanella, Bonaventura Clotet, Javier Martinez-Picado, Roger Badia, Eva Riveira-Muñoz, Ester Ballana

المصدر: Frontiers in Immunology, Vol 13 (2022)

مصطلحات موضوعية: IRF7, JAK-STAT signalling, HIV-1 cure strategies, latency reversal agents, innate immunity, Immunologic diseases. Allergy, RC581-607

الوصف: The persistence of latent HIV reservoirs allows for viral rebound upon antiretroviral therapy interruption, hindering effective HIV-1 cure. Emerging evidence suggests that modulation of innate immune stimulation could impact viral latency and contribute to the clearing of HIV reservoir. Here, the latency reactivation capacity of a subclass of selective JAK2 inhibitors was characterized as a potential novel therapeutic strategy for HIV-1 cure. Notably, JAK2 inhibitors reversed HIV-1 latency in non-clonal lymphoid and myeloid in vitro models of HIV-1 latency and also ex vivo in CD4+ T cells from ART+ PWH, albeit its function was not dependent on JAK2 expression. Immunophenotypic characterization and whole transcriptomic profiling supported reactivation data, showing common gene expression signatures between latency reactivating agents (LRA; JAK2i fedratinib and PMA) in contrast to other JAK inhibitors, but with significantly fewer affected gene sets in the pathway analysis. In depth evaluation of differentially expressed genes, identified a significant upregulation of IRF7 expression despite the blockade of the JAK-STAT pathway and downregulation of proinflammatory cytokines and chemokines. Moreover, IRF7 expression levels positively correlated with HIV latency reactivation capacity of JAK2 inhibitors and also other common LRAs. Collectively, these results represent a promising step towards HIV eradication by demonstrating the potential of innate immune modulation for reducing the viral reservoir through a novel pathway driven by IRF7.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2022.1001068/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/0c134c9371f546d1bf28e34f8645f39aTest

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

المصدر: Frontiers in Microbiology, Vol 13 (2022)

مصطلحات موضوعية: SARS-CoV-2 variants of concern, ACE2, viral load, histology, in silico modeling, infection, Microbiology, QR1-502

الوصف: The emerging SARS-CoV-2 variants of concern (VOCs) may display enhanced transmissibility, more severity and/or immune evasion; however, the pathogenesis of these new VOCs in experimental SARS-CoV-2 models or the potential infection of other animal species is not completely understood. Here we infected K18-hACE2 transgenic mice with B.1, B.1.351/Beta, B.1.617.2/Delta and BA.1.1/Omicron isolates and demonstrated heterogeneous infectivity and pathogenesis. B.1.351/Beta variant was the most pathogenic, while BA.1.1/Omicron led to lower viral RNA in the absence of major visible clinical signs. In parallel, we infected wildtype (WT) mice and confirmed that, contrary to B.1 and B.1.617.2/Delta, B.1.351/Beta and BA.1.1/Omicron can infect them. Infection in WT mice coursed without major clinical signs and viral RNA was transient and undetectable in the lungs by day 7 post-infection. In silico modeling supported these findings by predicting B.1.351/Beta receptor binding domain (RBD) mutations result in an increased affinity for both human and murine ACE2 receptors, while BA.1/Omicron RBD mutations only show increased affinity for murine ACE2.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmicb.2022.840757/fullTest; https://doaj.org/toc/1664-302XTest

الوصول الحر: https://doaj.org/article/e5998ef26b8d4519a29a11917fcf9b8eTest

المؤلفون: Dàlia Raïch-Regué, Jordana Muñoz-Basagoiti, Daniel Perez-Zsolt, Marc Noguera-Julian, Edwards Pradenas, Eva Riveira-Muñoz, Neus Giménez, Assumpta Carabaza, Francesc Giménez, Verónica Saludes, Elisa Martró, Neus Robert, Ignacio Blanco, Roger Paredes, Lidia Ruiz, Ester Ballana, Bonaventura Clotet, Julià Blanco, Nuria Izquierdo-Useros

المصدر: Frontiers in Microbiology, Vol 13 (2022)

مصطلحات موضوعية: SARS-CoV-2, diagnosis, antigen-detecting rapid diagnostic tests, variants of concern, nucleocapsid (N), Microbiology, QR1-502

الوصف: The SARS-CoV-2 antigen-detecting rapid diagnostic test (Ag-RDTs) is an easy-to-use diagnostic tool to identify the contagious individuals and reduce the new infections. However, to be effective, Ag-RDTs require the detection of distinct variants of concern (VOC) with high analytical sensitivity. Here, we found that the VOC diverge at the nucleocapsid protein used by four commercial Ag-RDTs for the viral detection. Relative to the original D614G variant, there was a 10-fold loss of detection for the Delta and Alpha variants in certain Ag-RDTs, a reduction above the threshold required to isolate the viable virus. However, Beta and Omicron variants did not lose the detection capacity. As the new VOC arise, successful contact tracing requires continuous monitoring of Ag-RDTs performance.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmicb.2022.810576/fullTest; https://doaj.org/toc/1664-302XTest

الوصول الحر: https://doaj.org/article/d729889f231e45efa83a56c02270eab8Test