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Research Lines

Content with Investigacion Inmunidad Humoral y Vacunas frente al VIH .

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:

  1. 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.
  2. Study of the effect of feminizing hormone therapy on the immune system of transgender women.
  3. 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.
  4. 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.
  5. 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.
  6. 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 Inmunidad Humoral y Vacunas frente al VIH .

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

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Provirus reactivation is impaired in HIV-1 infected individuals on treatment with dasatinib and antiretroviral therapy.

Provirus reactivation is impaired in HIV-1 infected individuals on treatment with dasatinib and antiretroviral therapy. Vigón L, Martínez-Román P, Rodríguez-Mora S, Torres M, Puertas MC, Mateos E, Salgado M, Navarro A, Sánchez-Conde M, Ambrosioni J, Cervero M, Wyen C, Hoffmann C, Miró JM, Alcamí J, Podzamczer D, García-Gutiérrez V, Martínez-Picado J, Briz V, Rosa López-Huertas M, Planelles V, Coiras M (AC). Biochem Pharmacol. 2021 Oct;192:114666. doi: 10.1016/j.bcp.2021.114666. PMID: 34186065.

PUBMED DOI

T-Cell-Specific Loss of the PI-3-Kinase p110α Catalytic Subunit Results in Enhanced Cytokine Production and Antitumor Response.

1. Aragoneses-Fenoll L, Ojeda G, Montes-Casado M, Acosta-Ampudia Y, Dianzani U, Portolés P, Rojo JM. T-Cell-Specific Loss of the PI-3-Kinase p110α Catalytic Subunit Results in Enhanced Cytokine Production and Antitumor Response. Front. Immunol. 2018 Feb 27;9:332.

PUBMED DOI

ETP-46321, a dual p110α/δ class IA phosphoinositide 3-kinase inhibitor modulates T lymphocyte activation and collagen-induced arthritis.

2. Aragoneses-Fenoll L, Montes-CasadoM, Ojeda G, Acosta YY, Herranz J, Martínez S, Blanco-Aparicio C, Criado G, Pastor J, Dianzani U, Portolés P, Rojo JM. ETP-46321, a dual p110α/δ class IA phosphoinositide 3-kinase inhibitor modulates T lymphocyte activation and collagen-induced arthritis. Biochem. Pharmacol. 2016 Apr 15;106:56-69. Epub 2016 Feb 13.

PUBMED DOI

Suppression of CD4+ T lymphocyte activation in vitro and experimental encephalomyelitis in vivo by the phosphatidyl inositol 3-kinase inhibitor PIK-75.

3. Acosta YY, Montes-Casado M, Aragoneses-Fenoll L, Dianzani U, Portoles P, Rojo JM. Suppression of CD4+ T lymphocyte activation in vitro and experimental encephalomyelitis in vivo by the phosphatidyl inositol 3-kinase inhibitor PIK-75. Int. J. Immunopathol. Pharmacol. 2014 Jan-Mar;27(1):53-67.

PUBMED DOI

Effects of 3D nanocomposite bioceramic scaffolds on the immune response

4. Cicuendez M., Portolés P., Montes-Casado M., Izquierdo-Barba I., Vallet-Regı M., and Portolés M.T. Effects of 3D nanocomposite bioceramic scaffolds on the immune response. J. Mater. Chem. B, 2014, 2 (22), 3469-3479.

DOI

Characteristics of TCR/CD3 complex CD3 chains of regulatory CD4+ T (Treg) lymphocytes: Role in Treg differentiation in vitro and impact on Treg in vivo.

5. Rojo, J. M., G. Ojeda, Y. Y. Acosta, M. Montes-Casado, G. Criado, and P. Portoles. Characteristics of TCR/CD3 complex CD3 chains of regulatory CD4+ T (Treg) lymphocytes: Role in Treg differentiation in vitro and impact on Treg in vivo. J. Leukoc. Biol. 2014, 95 (3): 441-450.

PUBMED DOI

Dissociation of actin polymerization and lipid raft accumulation by ligation of the Inducible Costimulator (ICOS, CD278)

6. Y. Acosta, G. Ojeda, M. P. Zafra, I. Seren-Bernardone, A. Sánchez, U. Dianzani, P. Portolés y J. M. Rojo. Dissociation of actin polymerization and lipid raft accumulation by ligation of the Inducible Costimulator (ICOS, CD278). Inmunología, 2012, 31 (1): 4-12.

DOI

Complement regulatory protein Crry/p65 costimulation expands natural Treg cells with enhanced suppressive properties in proteoglycan-induced arthritis.

7. Ojeda G., Pini E., Eguiluz C., Montes-Casado M., Broere F., van Eden W., Rojo J.M., and Portolés P. Complement regulatory protein Crry/p65 costimulation expands natural Treg cells with enhanced suppressive properties in proteoglycan-induced arthritis. Arthritis Rheum. 2011 Jun;63(6):1562-72.

PUBMED DOI

Biased binding of class IA phosphatidyl inositol 3-kinase subunits to inducible costimulator (CD278)

8. Acosta Y.Y., Zafra M.P., Ojeda G., Bernardone I.S., Dianzani U., Portolés P., Rojo J.M. Biased binding of class IA phosphatidyl inositol 3-kinase subunits to inducible costimulator (CD278). Cell. Mol. Life Sci. 2011 Sep;68(18):3065-79.

PUBMED DOI

Structure and Immunogenicity of the Human Metapneumovirus F Protein in the Postfusion Conformation.

5. Mas V, Rodriguez L, Olmedillas E, Cano O, Palomo C, Terron MC, et al. Engineering, Structure and Immunogenicity of the Human Metapneumovirus F Protein in the Postfusion Conformation. PLoS Pathog. 2016;12(9):e1005859.

PUBMED DOI

Essential in vitro diagnostics for advanced HIV and serious fungal diseases: international experts' consensus recommendations. Eur J Clin Microbiol Infect Dis. 2019 Sep

Bongomin F, Govender NP, Chakrabarti A, Robert-Gangneux F, Boulware DR, Zafar A, Oladele RO, Richardson MD, Gangneux JP, Alastruey-Izquierdo A, Bazira J, Boyles TH, Sarcarlal J, Nacher M, Obayashi T, Worodria W, Pasqualotto AC, Meya DB, Cheng B, Sriruttan C, Muzoora C, Kambugu A, Rodriguez Tudela JL, Jordan A, Chiller TM, Denning DW. Essential in vitro diagnostics for advanced HIV and serious fungal diseases: international experts' consensus recommendations. Eur J Clin Microbiol Infect Dis. 2019 Sep;38(9):1581-1584. doi: 10.1007/s10096-019-03600-4. PMID: 31175479.

PUBMED DOI

Godet C, Alastruey-Izquierdo A, Flick H, Hennequin C, Mikilps-Mikgelbs R, Munteanu O, Page I, Seidel D, Salzer HJF. A CPAnet consensus statement on research priorities for chronic pulmonary aspergillosis: a neglected fungal infection that requires attention. J Antimicrob Chemother. 2018 ​

Godet C, Alastruey-Izquierdo A, Flick H, Hennequin C, Mikilps-Mikgelbs R, Munteanu O, Page I, Seidel D, Salzer HJF. A CPAnet consensus statement on research priorities for chronic pulmonary aspergillosis: a neglected fungal infection that requires attention. J Antimicrob Chemother. 2018 Feb 1;73(2):280-286. doi: 10.1093/jac/dkx390. PMID: 29126309.​

PUBMED DOI

Genetic Characterization of Brucella spp.: Whole Genome Sequencing-Based Approach for the Determination of Multiple Locus Variable Number Tandem Repeat Profiles

Pelerito A, Nunes A, Grilo T, Isidro J, Silva C, Ferreira AC, Valdezate S, Núncio MS, Georgi E, Gomes JP. (2021) Genetic Characterization of Brucella spp.: Whole Genome Sequencing-Based Approach for the Determination of Multiple Locus Variable Number Tandem Repeat Profiles. 2021. Front Microbiol. 12;12:740068

PUBMED DOI

Saezia sanguinis gen. nov., sp. nov., a Betaproteobacteria member of order Burkholderiales, isolated from human blood

Medina-Pascual MJ, Monzón S, Villalón P, Cuesta I, González-Romo F, Valdezate S. (2020). Saezia sanguinis gen. nov., sp. nov., a Betaproteobacteria member of order Burkholderiales, isolated from human blood. Int J Syst Evol Microbiol.70:2016-25.

PUBMED DOI

Dynamics of a Sporadic Nosocomial Acinetobacter calcoaceticus-Acinetobacter baumannii Complex Population

Villalón P, Ortega M, Sáez-Nieto JA, Carrasco G, Medina-Pascual MJ, Garrido N, Valdezate S. (2019). Dynamics of a Sporadic Nosocomial Acinetobacter calcoaceticus-Acinetobacter baumannii Complex Population. 2019. Front Microbiol. 22;10:593

PUBMED DOI

Epidemiology and susceptibility to antimicrobial agents of the main Nocardia species in Spain.

Valdezate S, Garrido N, Carrasco G, Medina-Pascual MJ, Villalón P, Navarro AM, Saéz-Nieto JA. Epidemiology and susceptibility to antimicrobial agents of the main Nocardia species in Spain. J Antimicrob Chemother. 2017;72(3):754-761.

PUBMED DOI

Paenibacillus spp. isolated from human and environmental samples in Spain: detection of 11 new species.

Sáez-Nieto JA, Medina-Pascual MJ, Carrasco G, Garrido N, Fernandez-Torres MA, Villalón P, Valdezate S. Paenibacillus spp. isolated from human and environmental samples in Spain: detection of 11 new species. New Microbes New Infect. 2017. 24;19:19-27.

PUBMED DOI

Increase in isolation of Burkholderia contaminans from Spanish patients with cystic fibrosis.

Medina-Pascual MJ, Valdezate S, Carrasco G, Villalón P, Garrido N, Saéz-Nieto JA. (2015) Increase in isolation of Burkholderia contaminans from Spanish patients with cystic fibrosis. Clin Microbiol Infect. ;21(2):150-6

PUBMED DOI

Resistance gene pool to co-trimoxazole in non-susceptible Nocardia strains

Valdezate S, Garrido N, Carrasco G, Villalón P, Medina-Pascual MJ, Saéz-Nieto JA. (2015). Resistance gene pool to co-trimoxazole in non-susceptible Nocardia strains. Front Microbiol. 2015 Apr 28;6:376

PUBMED DOI

Genomic Background and Phylogeny of cfiA-Positive Bacteroides fragilis Strains Resistant to Meropenem-EDTA

Medina-Pascual MJ, Valdezate S, Carrasco G, Villalón P, Garrido N, Saéz-Nieto JA. (2015) Increase in isolation of Burkholderia contaminans from Spanish patients with cystic fibrosis. Clin Microbiol Infect. ;21(2):150-6.

PUBMED DOI

Content with Investigacion Inmunidad Humoral y Vacunas frente al VIH .

List of staff

Additional Information

Participation in research networks

Network Biomedical Research Center in Infectious Diseases
Participation: Member of the research team (Víctor Sánchez Merino); Coordinator of the "Preventive Vaccines against HIV-1" working group, HIV Program (Eloísa Yuste Herranz)
Funding agency: ISCIII
Duration: 2023 - Present
Code: CIBERINFEC, group CB21/13/00015

AIDS Research Network
Participation: Member of the research team (Víctor Sánchez Merino); Head of the bNAbs Detection and Characterization Working Group, Vaccine Program (Eloísa Yuste Herranz)
Funding agency: ISCIII
Duration: 01/01/2017-12/31/2021
Code: RETICS; RD16CIII/0002/0001

AIDS Research Network
Participation: Member of the research team (Víctor Sánchez Merino); Head of the Vaccine Development Working Group, Immunopathogenesis Program (Eloísa Yuste Herranz)
Funding agency: ISCIII
Duration: 01/01/2013-12/31/2017
Code: RETICS; RD12/0017

AIDS Research Network
Participation: Members of the research team (Víctor Sánchez Merino and Eloísa Yuste Herranz)
Funding agency: ISCIII
Duration: 04/04/2008-12/31/2013
Code: RETICS; RD12/0017

Supervised doctoral theses

Development of immunogens and vaccination strategies to optimize the induction of broad-spectrum neutralizing antibodies against HIV-1. Student: Carolina Beltrán Pávez. Thesis co-director: Víctor Sánchez Merino; Eloísa Yuste Herranz. Implementation entity: IDIBAPS / ISCIII / Universitat de Barcelona. Defense date: 11/26/2018. Grade obtained: Excellent Cum Laude

Characterization of the neutralizing response of patients with recent HIV-1 infection and isolation of antibodies. Student: Amanda Fabra García. Thesis co-director: Víctor Sánchez Merino; Eloísa Yuste Herranz. Implementation entity: IDIBAPS / Universitat de Barcelona. Defense date: 07/20/2017. Grade obtained: Excellent Cum Laude

Broadly neutralizing antibody responses against HIV-1: Characterization and design of new immunogens. Student: Carolina Barbosa Ferreira. Thesis co-director: Víctor Sánchez Merino; Eloísa Yuste Herranz. Implementation entity: IDIBAPS / Universitat de Barcelona. Defense date: 02/25/2013. Qualification obtained: Excellent Cum Laude (European Doctorate)

Participation in research networks

Network Biomedical Research Center in Infectious Diseases
Participation: Member of the research team (Víctor Sánchez Merino); Coordinator of the "Preventive Vaccines against HIV-1" working group, HIV Program (Eloísa Yuste Herranz)
Funding agency: ISCIII
Duration: 2023 - Present
Code: CIBERINFEC, group CB21/13/00015

AIDS Research Network
Participation: Member of the research team (Víctor Sánchez Merino); Head of the bNAbs Detection and Characterization Working Group, Vaccine Program (Eloísa Yuste Herranz)
Funding agency: ISCIII
Duration: 01/01/2017-12/31/2021
Code: RETICS; RD16CIII/0002/0001

AIDS Research Network
Participation: Member of the research team (Víctor Sánchez Merino); Head of the Vaccine Development Working Group, Immunopathogenesis Program (Eloísa Yuste Herranz)
Funding agency: ISCIII
Duration: 01/01/2013-12/31/2017
Code: RETICS; RD12/0017

AIDS Research Network
Participation: Members of the research team (Víctor Sánchez Merino and Eloísa Yuste Herranz)
Funding agency: ISCIII
Duration: 04/04/2008-12/31/2013
Code: RETICS; RD12/0017

Supervised doctoral theses

Development of immunogens and vaccination strategies to optimize the induction of broad-spectrum neutralizing antibodies against HIV-1. Student: Carolina Beltrán Pávez. Thesis co-director: Víctor Sánchez Merino; Eloísa Yuste Herranz. Implementation entity: IDIBAPS / ISCIII / Universitat de Barcelona. Defense date: 11/26/2018. Grade obtained: Excellent Cum Laude

Characterization of the neutralizing response of patients with recent HIV-1 infection and isolation of antibodies. Student: Amanda Fabra García. Thesis co-director: Víctor Sánchez Merino; Eloísa Yuste Herranz. Implementation entity: IDIBAPS / Universitat de Barcelona. Defense date: 07/20/2017. Grade obtained: Excellent Cum Laude

Broadly neutralizing antibody responses against HIV-1: Characterization and design of new immunogens. Student: Carolina Barbosa Ferreira. Thesis co-director: Víctor Sánchez Merino; Eloísa Yuste Herranz. Implementation entity: IDIBAPS / Universitat de Barcelona. Defense date: 02/25/2013. Qualification obtained: Excellent Cum Laude (European Doctorate)

Content with Investigacion Inmunidad Humoral y Vacunas frente al VIH .