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Investigation
Hepatitis C and other RNA virus
Research Lines
Content with Investigacion .
Classical viral vaccines rely on the induction of neutralizing antibodies. In the case of infection by the human immunodeficiency virus (HIV), the viral spike has evolved to evade recognition by these antibodies. Despite these obstacles, certain monoclonal antibodies capable of neutralizing the majority of primary HIV-1 isolates have been successfully isolated and have demonstrated efficacy both in controlling viremia and in providing protection against infection in animal models. These are known as broadly neutralizing antibodies (bNAbs).
In order to identify the factors involved in the induction of these antibodies and to develop preventive strategies based on bNAb induction, we are pursuing the following research lines:
- Determination of factors associated with the induction of effective humoral responses in different scenarios: recent infection, chronic infection, co-infection with hepatitis C virus, reinfection, and pediatric infection, among others.
- Study of the effect of feminizing hormone therapy on the immune system of transgender women.
- Development of HIV-1 vaccine prototypes based on viral spike proteins incorporated into Virus-Like Particles (VLPs) from two sources:
a) Selected from a library of randomly mutated spikes to enhance the accessibility of epitopes recognized by bNAbs.
b) Derived from viruses present in individuals with broad neutralizing responses in recent infection. - Isolation and characterization of new bNAbs against HIV-1 from individual B cells of individuals with an efficient neutralizing response. These antibodies could be used in both preventive and therapeutic strategies.
- Isolation of new monoclonal antibodies against other human pathogenic viruses, adapting the technology developed for HIV-1 antibody isolation, in collaboration with researchers from the National Center for Microbiology.
- Use of gene therapy vectors (Recombinant Adeno-Associated Viruses; rAAVs) to incorporate bNAbs and apply them in prophylactic and therapeutic strategies.
Research projects
Content with Investigacion .
Research Projects as Principal Investigators
Effect of Feminizing Hormone Therapy on the Immune Response in Transgender Women
Principal Investigator: Víctor Sánchez-Merino
Funding Agency: Intramural Health Strategic Action
Funding: €117,000
Participating Institutions: ISCIII, IRSICAIXA, 7 Infectious diseases units (Hospital General Universitario Gregorio Marañón (HGUGM-INF), Hospital Universitario La Paz (HULP), Hospital Universitario Infanta Leonor (HUIL), Hospital Fundación Jiménez Díaz (FJD), Fundación Universitario la Princesa (HUP), Hospital Universitario Ramón y Cajal (HURyC) y Hospital Universitario Doce de Octubre (HU12O), Centro Sandoval, 1 Gender Identity Unit, Facultad de psicología (UAM), Facultad de Geografía e Historia (UCM) and three ONGs
Duration: 01/01/2025- 31/12/2027
Project Reference: PI24CIII/00031
Design of Vaccine Prototypes based on HIV-1 Envelope presented on Virus-Like Particles and Nanodiscs
Principal Investigator: Eloísa Yuste Herranz
Funding agency: Knowledge Generation Projects. State Plan for Scientific and Technical Research and Innovation.
Funding: €125,000
Participating Institutions: ISCIII and University of UNSW (Sydney, Australia)
Duration: 01/09/24–31/12/28
Reference: Project PID2023-148729OB-100 funded by MICIU/AEI/10.13039/501100011033 and by FEDER, UE.
Funding for Research Assistant Position. Project: New Approaches to Immunogen Design for the Induction of Anti-HIV-1 Broadly Neutralizing Antibodies (bNAbs) Based on Viral Envelope Proteins Presented on VLPs
Principal Investigator: Eloísa Yuste Herranz
Funding Agency: Youth Employment Plan (Community of Madrid)
Funding: Hiring of a senior graduate for 2 years
Participating Institutions: ISCIII
Duration: 01/04/2024 – 31/03/2026
Project Reference: SAL-GL-28125
Generation of an Adenovirus-Associated Vector for the Delivery of a Broadly Neutralizing Antibody (bNAb) Against HIV-1 That Does Not Induce Anti-Antibody Responses. Funding for Research Assistant Position.
Principal Investigator: Víctor Sánchez Merino
Funding Agency: FUAX-Santander
Funding: €90,000
Participating Institutions: Universidad Alfonso X El Sabio and ISCIII
Duration: 01/04/2022 – 01/04/2025
Project Reference: 1.013.008
New Approaches to Immunogen Design for the Induction of Anti-HIV-1 Broadly Neutralizing Antibodies (bNAbs) Based on Viral Envelope Proteins Presented on Virus-Like Particles (VLPs).
Principal Investigator: Eloísa Yuste Herranz
Funding Agency: Intramural Health Strategic Action
Funding: €77,000
Participating Institutions: Fraunhofer Institute (Germany) and ISCIII
Duration: 01/01/2021 – 30/06/2024
Project Reference: PI20CIII/00039
Development of Immunogens and Vaccination Strategies to Optimize the Induction of Broadly Neutralizing Antibodies (bNAbs) Against HIV-1.
Principal Investigator: Eloísa Yuste Herranz
Funding Agency: Intramural Health Strategic Action
Funding: €117,000
Participating Institutions: Fraunhofer Institute (Germany) and ISCIII
Duration: 01/01/2018 – 31/12/2021
Personnel Hiring: One postdoctoral researcher for 3 years
Project Reference: PI17/00049
Isolation and Characterization of Broadly Neutralizing Antibodies Against HIV-1 from Recently Infected Patients.
Principal Investigator: Eloísa Yuste Herranz
Funding Agency: Health Strategic Action (ISCIII)
Funding: €57,475
Participating Institutions: IDIBAPS, Fraunhofer Institute (Germany), and ISCIII
Duration: 01/01/2014 – 30/04/2017
Project Reference: PI13/01528
Development of an HIV Vaccine: Isolation and Characterization of New Broadly Neutralizing Antibodies.
Principal Investigator: Eloísa Yuste Herranz
Funding Agency: Health Research Fund (ISCIII)
Funding: €116,765
Participating Institutions: IDIBAPS and ISCIII
Duration: 01/01/2010 – 31/12/2012
Project Reference: PI09/1459
Optimization of the HIV-1 Envelope Protein as an Immunogen.
Principal Investigator: Eloísa Yuste Herranz
Funding Agency: Spanish Foundation for AIDS Research and Prevention (FIPSE)
Funding: €141,845
Participating Institutions: IDIBAPS
Duration: 30/10/2008 – 31/08/2012
Personnel Hiring: One senior graduate for 3 years
Project Reference: 36780/08
Optimization of the HIV-1 Envelope Protein as an Immunogen.
Principal Investigator: Eloísa Yuste Herranz
Funding Agency: Ramón y Cajal Program (Ministry of Education and Science)
Funding: 5-year Ramón y Cajal Researcher contract + 3 years as I3
Participating Institutions: IDIBAPS
Duration: 2008 – 2016
Project Reference: RYC-2007-00788
R&D projects as part of the research team
Determination of factors associated with protection against Human Immunodeficiency Virus type 1 Reinfection: Identification of protection correlates.
Principal Investigator: María Pernas Escario
Funding Agency: Gilead Sciences
Funding: €16,630
Participating Entities: Centro Sandoval and ISCIII
Duration: 01/01/2023 - 31/12/2023
Contract/Project File: GLD22/001144
EAVI2020: European AIDS Vaccine Initiative 2020
Principal Investigator: José Alcamí Pertejo
Funding Agency: Horizon 2020 (European Union; EU)
Funding: €403,829
Participating Entities: ISCIII and an EU consortium
Duration: 01/01/2015 - 30/04/2021
Contract/Project File: MPY1398/15
EHVA, European HIV Vaccine Alliance (EHVA): an EU platform for the discovery and evaluation of novel prophylactic and therapeutic vaccine candidates.
Principal Investigator: Felipe García Alcaide
Funding Agency: Horizon 2020 (European Union; EU)
Funding: €1,000,000
Participating Entities: IDIBAPS and an EU consortium
Duration: 01/01/2018 - 31/12/2020
Contract/Project File: 681032
Grup de Recerca VIH/SIDA
Principal Investigator: José María Gatell
Funding Agency: AGAUR_SGR14 (Generalitat de Catalunya-projects)
Funding: €63,000
Participating Entities: IDIBAPS
Duration: 01/01/2014 - 30/04/2017
Contract/Project File: 214_SGR_706
SIDA Vaccine Research Project (HIVACAT)
Principal Investigator: José María Gatell
Funding Agency: MINECO (INNPACTO Program)
Funding: €288,740
Participating Entities: IDIBAPS and Irsicaixa
Duration: 01/01/2013 - 31/03/2020
Contract/Project File: PT-2012-0325-010000
Design, synthesis, and anti-HIV-1 study of peptide domains of GB virus B
Principal Investigator: Isabel Haro
Funding Agency: Foundation for AIDS Research and Prevention (FIPSE)
Funding: €33,000
Participating Entities: IQAC-CSIC and IDIBAPS
Duration: 09/03/2010 - 30/11/2014
Contract/Project File: 36-0735-09
Publications
9: Harvala H, Broberg E, Benschop K, Berginc N, Ladhani S, Susi P, Christiansen C, McKenna J, Allen D, Makiello P, McAllister G, Ca
9: Harvala H, Broberg E, Benschop K, Berginc N, Ladhani S, Susi P, Christiansen C, McKenna J, Allen D, Makiello P, McAllister G, Carmen M, Zakikhany K, Dyrdak R, Nielsen X, Madsen T, Paul J, Moore C, von Eije K, Piralla A, Carlier M, Vanoverschelde L, Poelman R, Anton A, López-Labrador FX, Pellegrinelli L, Keeren K, Maier M, Cassidy H, Derdas S, Savolainen-Kopra C, Diedrich S, Nordbø S, Buesa J, Bailly JL, Baldanti F, MacAdam A, Mirand A, Dudman S, Schuffenecker I, Kadambari S, Neyts J, Griffiths MJ, Richter J, Margaretto C, Govind S, Morley U, Adams O, Krokstad S, Dean J, Pons-Salort M, Prochazka B, Cabrerizo M, Majumdar M, Nebbia G, Wiewel M, Cottrell S, Coyle P, Martin J, Moore C, Midgley S, Horby P, Wolthers K, Simmonds P, Niesters H, Fischer TK. Recommendations for enterovirus diagnostics and characterisation within and beyond Europe. J Clin Virol. 2018 Apr; 101:11-17. doi: 10.1016/j.jcv.2018.01.008. Epub 2018 Feb 6. PMID: 29414181.
Inhibition of LpxC Increases Antibiotic Susceptibility in Acinetobacter baumannii
Inhibition of LpxC Increases Antibiotic Susceptibility in Acinetobacter baumannii. García-Quintanilla M, Caro-Vega JM, Pulido MR, Moreno-Martínez P, Pachón J, McConnell MJ. Antimicrob Agents Chemother. 2016 Jul 22;60(8):5076-9. doi: 10.1128/AAC.00407-16.
PUBMEDNew Panfungal Real-Time PCR Assay for Diagnosis of Invasive Fungal Infections.
4. Valero C, de la Cruz-Villar L, Zaragoza O, Buitrago MJ. New Panfungal Real-Time PCR Assay for Diagnosis of Invasive Fungal Infections. J Clin Microbiol. 2016 Dec;54(12):2910-2918. doi: 10.1128/JCM.01580-16. Epub 2016 Sep 14. PMID: 27629898.
DOIA Multiplex Real-Time PCR Assay for Identification of Pneumocystis jirovecii, Histoplasma capsulatum, and Cryptococcus neoformans/Cryptococcus gattii in Samples from AIDS Patients with Opportunistic Pneumonia
6. Gago S, Esteban C, Valero C, Zaragoza O, Puig de la Bellacasa J, Buitrago MJ. A multiplex real-time PCR assay for identification of Pneumocystis jirovecii, Histoplasma capsulatum, and Cryptococcus neoformans/Cryptococcus gattii in samples from AIDS patients with opportunistic pneumonia. J Clin Microbiol. 2014 Apr;52(4):1168-76. doi: 10.1128/JCM.02895-13. Epub 2014 Jan 29. PMID: 24478409.
PUBMED DOIAnalysis of strain relatedness using High Resolution Melting in a case of recurrent candiduria
7. Gago S, Lorenzo B, Gomez-Lopez A, Cuesta I, Cuenca-Estrella M, Buitrago MJ. Analysis of strain relatedness using high resolution melting in a case of recurrent candiduria. BMC Microbiol. 2013 Jan 23;13:13. doi: 10.1186/1471-2180-13-13. PMID: 23343107.
PUBMED DOIHigh-Resolution Melting Analysis for Identification of the Cryptococcus neoformans-Cryptococcus gattii Complex
8. Gago S, Zaragoza Ó, Cuesta I, Rodríguez-Tudela JL, Cuenca-Estrella M, Buitrago MJ. High-resolution melting analysis for identification of the Cryptococcus neoformans-Cryptococcus gattii complex. J Clin Microbiol. 2011 Oct;49(10):3663-6. doi: 10.1128/JCM.01091-11. Epub 2011 Aug 10. PMID: 21832024.
PUBMED DOIPerformance of Panfungal- and Specific-PCR-Based Procedures for Etiological Diagnosis of Invasive Fungal Diseases on Tissue Biopsy Specimens with Proven Infection: a 7-Year Retrospective Analysis from a Reference Laboratory
9. Buitrago MJ, Bernal-Martinez L, Castelli MV, Rodriguez-Tudela JL, Cuenca-Estrella M Performance of panfungal--and specific-PCR-based procedures for etiological diagnosis of invasive fungal diseases on tissue biopsy specimens with proven infection: a 7-year retrospective analysis from a reference laboratory. J Clin Microbiol. 2014 May;52(5):1737-40. doi: 10.1128/JCM.00328-14. Epub 2014 Feb 26.PMID: 24574295.
PUBMED DOIEpidemiología actual y diagnóstico de laboratorio de las micosis endémicas en España
11. Buitrago MJ, Cuenca-Estrella M. [Current epidemiology and laboratory diagnosis of endemic mycoses in Spain]. Enferm Infecc Microbiol Clin. 2012 Aug;30(7):407-13. doi: 10.1016/j.eimc.2011.09.014. Epub 2011 Nov 29. PMID: 22130575 Review. Spanish.
PUBMED DOIA matrix-assisted laser desorption/ionization time of flight mass spectrometry reference database for the identification of Histoplasma capsulatum
12. Buitrago MJ, Bernal-Martínez L, Castelli MV, Rodríguez-Tudela JL, Cuenca-Estrella M. Histoplasmosis and paracoccidioidomycosis in a non-endemic area: a review of cases and diagnosis. J Travel Med. 2011 Jan-Feb;18(1):26-33. doi: 10.1111/j.1708-8305.2010.00477.x. Epub 2010 Nov 28. PMID: 21199139.
PUBMED DOICopy Number Variation of Mitochondrial DNA Genes in Pneumocystis jirovecii According to the Fungal Load in BAL Specimens
13. Valero C, Buitrago MJ, Gago S, Quiles-Melero I, García-Rodríguez J. A matrix-assisted laser desorption/ionization time of flight mass spectrometry reference database for the identification of Histoplasma capsulatum. Med Mycol. 2018 Apr 1;56 (3):307-314. doi: 10.1093/mmy/myx047. PMID: 28992262.
PUBMED DOICopy Number Variation of Mitochondrial DNA Genes in Pneumocystis jirovecii According to the Fungal Load in BAL Specimens
14. Valero C, Buitrago MJ, Gits-Muselli M, Benazra M, Sturny-Leclère A, Hamane S, Guigue N, Bretagne S, Alanio A. Copy Number Variation of Mitochondrial DNA Genes in Pneumocystis jirovecii According to the Fungal Load in BAL Specimens. Front Microbiol. 2016 Sep 12;7:1413. doi: 10.3389/fmicb.2016.01413. eCollection 2016. PMID: 27672381.
PUBMED DOIIdentification of Off-Patent Compounds That Present Antifungal Activity Against the Emerging Fungal Pathogen Candida auris
2: de Oliveira HC, Monteiro MC, Rossi SA, Pemán J, Ruiz-Gaitán A, Mendes- Giannini MJS, Mellado E, Zaragoza O. Identification of Off-Patent Compounds That Present Antifungal Activity Against the Emerging Fungal Pathogen Candida auris. Front Cell Infect Microbiol. 2019 Apr 2;9:83. PMCID: PMC6454888.
PUBMED DOICryptococcus neoformans can form titan-like cells in vitro in response to multiple signals
Trevijano-Contador N, de Oliveira HC, García-Rodas R, Rossi SA, Llorente I, Zaballos Á, Janbon G, Ariño J, Zaragoza Ó. Cryptococcus neoformans can form titan-like cells in vitro in response to multiple signals. PLoS Pathog. 2018 May 18;14(5):e1007007. PMCID: PMC6454888.
PUBMED DOICell Wall Changes in Amphotericin B-Resistant Strains from Candida tropicalis and Relationship with the Immune Responses Elicited by the Host
5: Mesa-Arango AC, Rueda C, Román E, Quintin J, Terrón MC, Luque D, Netea MG, Pla J, Zaragoza O. Cell Wall Changes in Amphotericin B-Resistant Strains from Candida tropicalis and Relationship with the Immune Responses Elicited by the Host. Antimicrob Agents Chemother. 2016 Mar 25;60(4):2326-35. PMCID: PMC4808153.
PUBMED DOIThe production of reactive oxygen species is a universal action mechanism of Amphotericin B against pathogenic yeasts and contributes to the fungicidal effect of this drug
8: Mesa-Arango AC, Trevijano-Contador N, Román E, Sánchez-Fresneda R, Casas C, Herrero E, Argüelles JC, Pla J, Cuenca-Estrella M, Zaragoza O. The production of reactive oxygen species is a universal action mechanism of Amphotericin B against pathogenic yeasts and contributes to the fungicidal effect of this drug. Antimicrob Agents Chemother. 2014 Nov;58(11):6627-38. PMCID: PMC4249417.
PUBMED DOICapsule Growth in Cryptococcus neoformans Is Coordinated with Cell Cycle Progression
9: García-Rodas R, Cordero RJ, Trevijano-Contador N, Janbon G, Moyrand F, Casadevall A, Zaragoza O. Capsule growth in Cryptococcus neoformans is coordinated with cell cycle progression. mBio. 2014 Jun 17;5(3):e00945-14. PMCID: PMC4056547.
PUBMED DOIThe interaction between Candida krusei and murine macrophages results in multiple outcomes, including intracellular survival and escape from killing
12: García-Rodas R, González-Camacho F, Rodríguez-Tudela JL, Cuenca-Estrella M, Zaragoza O. The interaction between Candida krusei and murine macrophages results in multiple outcomes, including intracellular survival and escape from killing. Infect Immun. 2011 Jun;79(6):2136-44. PMCID: PMC3125833.
PUBMED DOIHuman IgM Inhibits the Formation of Titan-Like Cells in Cryptococcus neoformans
14: Trevijano-Contador N, Pianalto KM, Nichols CB, Zaragoza O, Alspaugh JA, Pirofski LA. Human IgM Inhibits the Formation of Titan-Like Cells in Cryptococcus neoformans. Infect Immun. 2020 Mar 23;88(4):e00046-20. PMCID: PMC7093138.
PUBMED DOIThe lymphocyte scavenger receptor CD5 plays a nonredundant role in fungal infection
15: Velasco-de-Andrés M, Català C, Casadó-Llombart S, Simões I, Zaragoza O, Carreras E, Lozano F. The lymphocyte scavenger receptor CD5 plays a nonredundant role in fungal infection. Cell Mol Immunol. 2020 Apr 24.
PUBMED DOIContent with Investigacion .
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Eloisa Yuste Herranz
Staff Scientist
ORCID code: 0000-0002-9484-9974
She holds a Bachelor's and a Ph.D. in Biological Sciences from the Complutense University of Madrid. She completed her first postdoctoral stay (1998–2001) at the “Severo Ochoa” Molecular Biology Center (Madrid). In 2001, she undertook a second postdoctoral stay at Harvard Medical School (USA), where she was promoted to Associate Researcher in 2005.
In 2008, she joined the August Pi i Sunyer Biomedical Research Institute (Barcelona) as a Ramón y Cajal Researcher, later being promoted to I3 Researcher in 2011 at the same institution. In 2016, she joined the National Center for Microbiology at the Carlos III Health Institute (Madrid) as a Distinguished Researcher. In 2018, she was promoted to Tenured Scientist at the same institution.
Her research has focused on the study of humoral immunity against HIV-1 and the development of preventive HIV-1 vaccine prototypes. She is currently co-leading, alongside Dr. Víctor Sánchez Merino, the newly established Humoral Immunity and HIV Vaccines Unit.
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Victor Sánchez Merino
Distinguished Scientist
ORCID code: 0000-0001-9400-427X
He holds a Bachelor's and a Ph.D. in Pharmacy from the Complutense University of Madrid, specializing in virology and molecular biology. His research has focused on the study of HIV and EBV. His doctoral thesis addressed the evolution of HIV-1 and the restoration of mutant HIV-1 reverse transcriptase function.
He completed a postdoctoral stay at Harvard University, investigating new viral interactions (2001–2003). At the University of Massachusetts, he explored CD8+ T lymphocyte responses in vertical HIV transmission (2003–2008).
In Spain, at the Hospital Clínico-IDIBAPS (Barcelona; 2008–2017) and the Carlos III Health Institute (Madrid; 2017–Present), he has led research on HIV-1 neutralizing antibodies and the design of preventive vaccines.He is currently co-leading, alongside Dr. Eloísa Yuste Herranz, the newly established Humoral Immunity and HIV Vaccines Unit. Additionally, he is a professor and principal investigator at Alfonso X el Sabio University (Madrid).
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Almudena Rubio Perez
Research Assistant
ORCID code: 0009-0006-4687-7555
Graduated in Biochemistry from the University of Córdoba (Andalusia, Spain) with a master's degree in Biomedicine from the University of Cádiz (Andalusia, Spain). She is currently part of the Humoral Immunity and HIV Vaccines Unit (IHV) at the National Center for Microbiology (CNM) under a Youth Guarantee contract funded by the Community of Madrid and is pursuing a Ph.D. in the Microbiology and Parasitology program at the Complutense University of Madrid.
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Lorena Vigón Hernandez
Tenured Specialized Technician from OPIs
ORCID code: 0000-0002-6405-4054
Graduate in Health Biology and PhD in Health Sciences from the University of Alcalá de Henares. In 2016, she joined the CNM-ISCIII under a Youth Guarantee contract funded by the Community of Madrid, and in 2018 she was awarded a pFIS fellowship, which enabled her to remain at the same institution. Subsequently, in 2022, she was appointed as a Tenured Specialized Technical Staff of the Spanish Public Research Organizations (OPIs).
Her research has primarily focused on elucidating the mechanism of action of tyrosine kinase inhibitors in HIV-1 infection (PMID: 32828803; PMID: 34186065), as well as on the identification of biomarkers that could predict COVID-19 severity (PMID: 34616404; PMID: 34122423; PMID: 35960731).
She is currently a member of the recently established Humoral Immunity and HIV Vaccines Unit, led by Dr. Eloisa Yuste and Dr. Victor Sanchez-Merino.
Actualmente forma parte de la recientemente creada Unidad de Inmunidad Humoral y Vacunas frente al VIH, liderada por la Dra. Eloísa Yuste Herranz y el Dr. Víctor Sánchez Merino.
List of staff