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Investigation

Pneumococcus

Research Lines

Content with Investigacion Inmunopatología del SIDA .

Research Lines:

1.    Molecular mechanisms associated to the protection of HIV-1 infection in limb-girdle muscular dystrophy dominant D2 (LGMDD2) patients.
2.    Generation of neutralizing antibodies for therapeutic use based on the broad-spectrum neutralizing response against founder viruses.
3.    Characterization of the immune memory against SARS-CoV-2 in a population over 65 years of age.
4.    Screening and characterization of new anti-latency drugs against HIV-1.
5.    Study of viral entry and HIV tropism in viruses of special epidemiological relevance in Spain. 
6.    Genetic mechanisms of protection and control of HIV-1 infection in populations with extreme phenotypes.

Clinical studies:

1.    Phase 1 clinical trial to evaluate the safety and immunogenicity of HIV-1 envelope-based 763SIP8/MPLA-5 vaccine as a preventive vaccine in healthy uninfected adults. 
2.    ENE-COVID-Senior: Prospective observational study in a cohort of elderly nursing home residents to establish their immune status after receiving a complete vaccination regimen.

Implementation of new technologies:

1.    Identification of HIV-1 integration sites by deep sequencing.
2.    Single cell transcriptomics with simultaneous TCR/BCR sequencing.
3.    Epidemiological intelligence for prediction of SARS-CoV-2 variants likely to emerge in different vaccination settings.
 

Research projects

Content with Investigacion Inmunopatología del SIDA .

1.    Immune response to SARS-CoV-2 infection: effect in naïve vaccinees and seropositives against the most transmissible variants and relevance of host genetics.
Principal Investigator: Javier García Pérez. 
Funding Agency: Acción Estratégica en Salud Intramural 2021(ISCIII)
Funding: 135.000 €
Duration: 2022-2025. 
Project Reference: PI21CIII/00025.
2.    Design and generation of viral stocks of new SARS-CoV-2 variants (omicron subvariants) and analysis of their susceptibility to antibodies neutralization.
Principal Investigator: Javier García Pérez.
Funding Agency: Hipra Scientific S.L.U.
Funding: 103.771 €
Duration: 2023-2025.
Project Reference: MVP 198/23.
3.    Characterization of a mutation in transportin 3 that protects against HIV infection: molecular mechanisms and discovery of new drugs.
Principal Investigator: José Alcamí y Javier García Pérez.
Funding Agency:     Proyectos de I+D+I, Generación de Conocimiento y Retos Investigación de la Agencia Estatal de Investigación.
Funding: 240.000 €
Duration: 2022-2026. 
Project Reference: PID2021-125978OB-C21 funded by MICIU/AEI/10.13039/501100011033 and by FEDER, UE

4.    Generation of immunogens based on HIV-1 envelopes from acutely infected individuals with a broad neutralizing response against founder viruses.
Principal investigator: Nuria González Fernández.
Funding Agency: Acción Estratégica en Salud Intramural 2023 (ISCIII)
Funding: 82.000 €
Duration: 2024-2026. 
Project Reference: PI23CIII/00039.
5.    Phase 1 clinical trial to evaluate the safety and immunogenicity of HIV-1 envelope-based 763SIP8/MPLA-5 vaccine. 
Principal Investigator: Josep Mallolas Masferrer.
Funding Agency: Proyectos de Investigación Clínica Independiente, Acción Estratégica en Salud 2021-2023 (ISCIII).
Funding: 173.200 €
Duration: 2024-2026. 
Project Reference: ICI23/00025.
6.    Service of immunological determinations of the ENE-COVID SENIOR II protocol.
Principal Investigator: Mayte Pérez Olmeda y Javier García Pérez. 
Funding Agency: Fundación para la investigación biomédica del Hospital Universitario La Paz
Funding: 185.037 €
Duration: 2024-2025. 
Project Reference: MOTR 219/24.
7.    Characterization of the immune memory against SARS-CoV-2 in a population over 65 years of age using single cell transcriptomics.
Principal Investigator: Javier García Pérez y Francisco Díez Fuertes.
Funding Agency: Acción Estratégica en Salud Intramural 2021(ISCIII)
Funding: 152.000 €
Duration: 2025-2027. 
Project Reference: PI24CIII/00058
8. Evaluation of rimonabant and cannbinooid analogues in HIV infection and viral latency.
Principal Investigator: Luis Miguel Bedoya del Olmo. 
Funding Agency: Universidad Complutense de Madrid
Funding: 12.000 €
Duration: 2024-2025. 
Project Reference: PR12/24-31553.
9. Discovery of new inhibitors of HIV-1 RNA biogenesis based on blocking the ribonucleoprotein RRE-Rev.
Principal Investigator: José Gallego Sala. Associate Researcher: Luis Miguel Bedoya del Olmo
Funding Agency: Department of Innovation, Universities, Science and Digital Society. Generalitat Valenciana.
Funding: 543,683.84 €
Duration: 2025-2027. 
Project Reference: PROMETEO/2021/036.

Publications

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Systematic analysis of intracellular trafficking motifs located within the cytoplasmic domain of simian immunodeficiency virus glycoprotein gp41

Postler TS, Bixby JG, Desrosiers RC, Yuste E; PLoS One. 2014 Dec 5;9(12):e114753

PUBMED DOI

Evolution of broadly cross-reactive HIV-1-neutralizing activity: therapy-associated decline, positive association with detectable viremia, and partial restoration of B-cell subpopulations

Ferreira CB, Merino-Mansilla A, Llano A, Perez I, Crespo I, Llinas L, Garcia F, Gatell JM, Yuste E, Sanchez-Merino V; J Virol. 2013 Nov;87(22):12227-36

PUBMED DOI

Human immunodeficiency virus type 1 and related primate lentiviruses engage clathrin through Gag-Pol or Gag

Popov S, Strack B, Sanchez-Merino V, Popova E, Rosin H, Gottlinger HG; J Virol. 2011 Apr;85(8):3792-801

PUBMED DOI

Definition of the viral targets of protective HIV-1-specific T cell responses

Mothe B, Llano A, Ibarrondo J, Daniels M, Miranda C, Zamarreno J, Bach V, Zuniga R, Perez-Alvarez S, Berger CT, Puertas MC, Martinez-Picado J, Rolland M, Farfan M, Szinger JJ, Hildebrand WH, Yang OO, Sanchez-Merino V, Brumme CJ, Brumme ZL, Heckerman D, Allen TM, Mullins JI, Gomez G, Goulder PJ, Walker BD, Gatell JM, Clotet B, Korber BT, Sanchez J, Brander C; J Transl Med. 2011 Dec 7;9:208

PUBMED DOI

Broadly cross-neutralizing antibodies in HIV-1 patients with undetectable viremia

Medina-Ramirez M, Sanchez-Merino V, Sanchez-Palomino S, Merino-Mansilla A, Ferreira CB, Perez I, Gonzalez N, Alvarez A, Alcocer-Gonzalez JM, Garcia F, Gatell JM, Alcami J, Yuste E; J Virol. 2011 Jun;85(12):5804-13.

PUBMED DOI

Vector-mediated gene transfer engenders long-lived neutralizing activity and protection against SIV infection in monkeys

Johnson PR, Schnepp BC, Zhang J, Connell MJ, Greene SM, Yuste E, Desrosiers RC, Clark KR; Nat Med. 2009 Aug;15(8):901-6

PUBMED DOI

Identification and characterization of HIV-1 CD8+ T cell escape variants with impaired fitness

Sanchez-Merino V, Farrow MA, Brewster F, Somasundaran M, Luzuriaga K; J Infect Dis. 2008 Jan 15;197(2):300-8

PUBMED DOI

Glycosylation of gp41 of simian immunodeficiency virus shields epitopes that can be targets for neutralizing antibodies

Yuste E, Bixby J, Lifson J, Sato S, Johnson W, Desrosiers R*. 2008. J Virol 82:12472-86.

PUBMED DOI

Simian immunodeficiency virus engrafted with human immunodeficiency virus type 1 (HIV-1)-specific epitopes: replication, neutralization, and survey of HIV-1-positive plasma

Yuste E, Sanford HB, Carmody J, Bixby J, Little S, Zwick MB, Greenough T, Burton DR, Richman DD, Desrosiers RC, Johnson WE*. 2006. J Virol 80:3030-41.

PUBMED DOI

Balancing selection and the evolution of functional polymorphism in Old World monkey TRIM5alpha

Newman RM, Hall L, Connole M, Chen GL, Sato S, Yuste E, Diehl W, Hunter E, Kaur A, Miller GM, Johnson WE; Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):19134-9

PUBMED DOI

Virion envelope content, infectivity, and neutralization sensitivity of simian immunodeficiency virus

Yuste E, Johnson W, Pavlakis GN, Desrosiers RC; J Virol. 2005 Oct;79(19):12455-63.

PUBMED DOI

HIV-1-specific CD8+ T cell responses and viral evolution in women and infants

Sanchez-Merino V, Nie S, Luzuriaga K*. 2005. J Immunol 175:6976-86.

PUBMED DOI

Modulation of Env content in virions of simian immunodeficiency virus: correlation with cell surface expression and virion infectivity

Yuste E, Reeves JD, Doms RW, Desrosiers RC*. 2004. J Virol 78:6775-85.

PUBMED DOI

The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ Ratios

Sanchez-Merino V, Martin-Serrano M, Beltran M, Lazaro-Martin B, Cervantes E, Oltra M, Sainz T, Garcia F, Navarro ML, Yuste E; Vaccines (Basel). 2023 Dec 20;12(1):8;

PUBMED DOI

High-Resolution Melting Assay to Detect the Mutations That Cause the Y132F and G458S Substitutions at the ERG11 Gene Involved in Azole Resistance in Candida parapsilosis

Nuria Trevijano-Contador, Elena López-Peralta, Jorge López-López, Alejandra Roldán, Cristina de Armentia, Óscar Zaragoza. Mycoses 2024 Nov;67(11):e13811

PUBMED DOI

Broad Protection against Invasive Fungal Disease from a Nanobody Targeting the Active Site of Fungal β-1,3-Glucanosyltransferases

Redrado-Hernández S, Macías-León J, Castro-López J, Belén Sanz A, Dolader E, Arias M, González-Ramírez AM, Sánchez-Navarro D, Petryk Y, Farkaš V, Vincke C, Muyldermans S, García-Barbazán I, Del Agua C, Zaragoza O, Arroyo J, Pardo J, Gálvez EM, Hurtado-Guerrero R. Angew Chem Int Ed Engl. 2024 Aug 19;63(34):e202405823.

PUBMED DOI

Toward the consensus of definitions for the phenomena of antifungal tolerance and persistence in filamentous fungi.

Amich J, Bromley M, Goldman GH, Valero C. mBio. 2025 Feb 25:e0347524

PUBMED DOI

Fungal burden assessment in hospital zones with different protection degrees

García-Gutiérrez L, Baena Rojas B, Ruiz M, Hernández Egido S, Ruiz-Gaitán AC, Laiz L, Pemán J, Cuétara-García MS, Mellado E & Martin-Sanchez PM. Build Environ, Volume 269, 1 February 2025, 112454

DOI

Distribution of Aspergillus Species and Prevalence of Azole Resistance in clinical and environmental Samples from a Spanish Hospital during a three-year study period

Lucio J, Alcazar-Fuoli L, Gil H, Cano-Pascual S, Hernandez-Egido S, Cuetara MS and Mellado E. Mycoses. 2024 Apr;67(4):e13719.

PUBMED DOI

Importance of the Aspergillus fumigatus mismatch repair protein Msh6 in antifungal resistance development

Lucio J, Gonzalez-Jimenez I, Roldan A, Amich J, Alcazar-Fuoli L and Mellado E. J Fungi (Basel). 2024 Mar 12;10(3):210

PUBMED DOI

Content with Investigacion Inmunopatología del SIDA .

List of staff

Additional Information

The Pneumococcus Unit is in charge of two very important aspects related to pneumococcus infections, such as epidemiological surveillance and basic and translational research of diseases caused by this pathogen. Our unit contributes to the epidemiological surveillance of invasive pneumococcal disease (IPD), characterizing the serotypes and genotypes of invasive pneumococci circulating in Spain, as well as the evolution of antibiotic resistance in this pathogen. 

Identification of culture-negative samples (CSF and pleural fluids) is performed using real-time PCR. Serotyping is performed using the Dot-blot and PCR-sequencing technique. Genotyping for the study of outbreaks and characterization of clones associated with hypervirulent and/or multiresistant strains is performed using the MLST technique and the analysis of complete genomes by massive sequencing. In addition, antibiotic susceptibility is determined following the EUCAST criteria. 

Our unit belongs to the IBD-labnet network of the ECDC and annually notifies all cases of IPD to the ECDC and also to the IRIS (Invasive Respiratory Infection Surveillance) network. At the level of basic and translational research, our unit is responsible for studying and characterizing different molecular mechanisms of pathogenicity and protection related to pneumococcal infection. Among the main objectives are the molecular characterization of virulence factors, the study of different vaccine candidate proteins and determining the possible impact that tobacco smoke and the formation of biofilms have on the colonization of the respiratory tract.

The Pneumococcus Unit is in charge of two very important aspects related to pneumococcus infections, such as epidemiological surveillance and basic and translational research of diseases caused by this pathogen. Our unit contributes to the epidemiological surveillance of invasive pneumococcal disease (IPD), characterizing the serotypes and genotypes of invasive pneumococci circulating in Spain, as well as the evolution of antibiotic resistance in this pathogen. 

Identification of culture-negative samples (CSF and pleural fluids) is performed using real-time PCR. Serotyping is performed using the Dot-blot and PCR-sequencing technique. Genotyping for the study of outbreaks and characterization of clones associated with hypervirulent and/or multiresistant strains is performed using the MLST technique and the analysis of complete genomes by massive sequencing. In addition, antibiotic susceptibility is determined following the EUCAST criteria. 

Our unit belongs to the IBD-labnet network of the ECDC and annually notifies all cases of IPD to the ECDC and also to the IRIS (Invasive Respiratory Infection Surveillance) network. At the level of basic and translational research, our unit is responsible for studying and characterizing different molecular mechanisms of pathogenicity and protection related to pneumococcal infection. Among the main objectives are the molecular characterization of virulence factors, the study of different vaccine candidate proteins and determining the possible impact that tobacco smoke and the formation of biofilms have on the colonization of the respiratory tract.

Content with Investigacion Inmunopatología del SIDA .