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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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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

Molecular characterization of invasive serogroup B Neisseria meningitidis isolates from Spain during 2015-2018: Evolution of the vaccine antigen factor H binding protein (FHbp)

Abad R, García-Amil C, Navarro C, Martín E, Martín-Díaz A, Vázquez JA. J Infect. 2021 Apr;82(4):37-44

PUBMED DOI

The fluoroquinolone levofloxacin triggers the transcriptional activation of iron transport genes that contribute to cell death in Streptococcus pneumoniae.

Ferrándiz MJ, de la Campa AG. Antimicrob Agents Chemother. 58:247-257 (2014)

PUBMED DOI

The formation of titan cells in Cryptococcus neoformans depends on the mouse strain and correlates with induction of Th2-type responses

García-Barbazán, I., Trevijano-Contador, N., Rueda, C., de Andrés, B., Pérez-Tavárez, R., Herrero-Fernández, I., Gaspar ML., and Zaragoza, O. Cellular Microbiology (2015) 18:111-124

PUBMED DOI

Carbapenemase-Producing Klebsiella pneumoniae From Transplanted Patients in Brazil: Phylogeny, Resistome, Virulome and Mobile Genetic Elements Harboring blaKPC-2 or blaNDM-1.

16. Carbapenemase-Producing Klebsiella pneumoniae From Transplanted Patients in Brazil: Phylogeny, Resistome, Virulome and Mobile Genetic Elements Harboring blaKPC-2 or blaNDM-1. Autores: Raro OHF, da Silva RMC, Filho EMR, Sukiennik TCT, Stadnik C, Dias CAG, Oteo Iglesias J, Pérez-Vázquez M. Revista: Front Microbiol. 2020 Jul 15;11:1563.

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

High susceptibility to zoliflodacin and conserved target (GyrB) for zoliflodacin among 1209 consecutive clinical Neisseria gonorrhoeae isolates from 25 European countries, 2018.

Unemo M, Ahlstrand J, Sánchez-Busó L, Day M, Aanensen D, Golparian D, Jacobsson S, Cole MJ, Torreblanca RA, Ásmundsdóttir LR, Balla E, De Baetselier I, Bercot B, Carannante A, Caugant D, Borrego MJ, Buder S, Cassar R, Cole M, Dam A, Eder C, Hoffmann S, Hunjak B, Jeverica S, Kirjavainen V, Maikanti-Charalambous P, Miriagou V, Mlynarczyk-Bonikowska B, Pakarna G, Patterson L, Pavlik P, Perrin M, Shepherd J, Stefanelli P, Unemo M, Jelena V, Zákoucká H. J Antimicrob Chemother. 2021 Feb 10:dkab024

PUBMED DOI

Fluoroquinolone-resistant pneumococci: dynamics of serotypes and clones in Spain in 2012 compared with those from 2002 and 2006

Domenech A, Tirado-Vélez JM, Fenoll A, Ardanuy C, Yuste J, Liñares J, de la Campa AG. Antimicrob Agents Chemother. 58:2393-2399 (2014).

PUBMED DOI

DNGR-1+ dendritic cells are located in meningeal and choroid plexus membranes of the non-injured brain.

Quintana, E., Fernández. A, de Andrés, B., Liste, I., Sancho, D., Gaspar, ML. and Cano, E. Glia (2015) 62 (12):2231-2248

PUBMED DOI

Dissemination of extensively drug-resistant NDM-producing Providencia stuartii in Europe linked to patients transferred from Ukraine, March 2022 to March 2023

17. Dissemination of extensively drug-resistant NDM-producing Providencia stuartii in Europe linked to patients transferred from Ukraine, March 2022 to March 2023. Autores: Witteveen S, Hans JB, Izdebski R, Hasman H, Samuelsen Ø, Dortet L, Pfeifer Y, Delappe N, Oteo-Iglesias J, Żabicka D, Cormican M, Sandfort M, Reichert F, Pöntinen AK, Fischer MA, Verkaik N, Pérez-Vazquez M, Pfennigwerth N, Hammerum AM, Hallstrøm S, Biedrzycka M, Räisänen K, Wielders CC, Urbanowicz P, de Haan A, Westmo K, Landman F, van der Heide HG, Lansu S, Zwittink RD, Notermans DW, Guzek A, Kondratiuk V, Salmanov A, Haller S, Linkevicius M, Gatermann S, Kohlenberg A, Gniadkowski M, Werner G, Hendrickx AP. Revista: Euro Surveill. 2024 Jun;29(23):2300616.

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

Meningococcal Serogroup B Disease in Vaccinated Children

Soler-Garcia A, Fernández de Sevilla M, Abad R, Esteva C, Alsina L, Vázquez J, Muñoz-Almagro C, Noguera-Julian A. J Pediatric Infect Dis Soc. 2020 Sep 17;9(4):454-459

PUBMED DOI

Postnatal and adult immunoglobulin repertoires of innate-like CD19(+)CD45R(lo) B Cells.

Prado, C., Rodriguez, M., Cortegano I., Ruiz, C., Alía, M., de Andrés, B., Gaspar, ML. J Inn Inmmunol. (2014) 6: 499-514

PUBMED DOI

Characterization of Carbapenemase-Producing Klebsiella oxytoca in Spain, 2016-2017.

18. Characterization of Carbapenemase-Producing Klebsiella oxytoca in Spain, 2016-2017. Autores: Pérez-Vazquez M, Oteo-Iglesias J, Sola-Campoy PJ, Carrizo-Manzoni H, Bautista V, Lara N, Aracil B, Alhambra A, Martínez-Martínez L, Campos J; Spanish Antibiotic Resistance Surveillance Program Collaborating Group. Revista: Antimicrob Agents Chemother. 2019 May 24;63(6): e02529-18.

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

The global meningitis genome partnership

Rodgers E, Bentley SD, Borrow R, Bratcher HB, Brisse S, Brueggemann AB, Caugant DA, Findlow J, Fox L, Glennie L, Harrison LH, Harrison OB, Heyderman RS, van Rensburg MJ, Jolley KA, Kwambana-Adams B, Ladhani S, LaForce M, Levin M, Lucidarme J, MacAlasdair N, Maclennan J, Maiden MCJ, Maynard-Smith L, Muzzi A, Oster P, Rodrigues CMC, Ronveaux O, Serino L, Smith V, van der Ende A, Vázquez J, Wang X, Yezli S, Stuart JM. J Infect. 2020; 81(4): 510-520

PUBMED DOI

Notch1 regulates progenitor cell proliferation and differentiation during murine yolk sac hematopoiesis

Isabel Cortegano, Pedro Melgar-Rojas, Luis Luna-Zurita, Miguel Ángel Rodríguez-Marcos, MA., Gaspar ML., and José Luis de la Pompa, JL. Cell death and diff. (2014) 21: 1081-1094

PUBMED DOI

Spread of the FAR-MRSA clone, a fusidic acid- and meticillin-resistant Staphylococcus aureus ST121, Europe, 2014 to 2024.

19. Spread of the FAR-MRSA clone, a fusidic acid- and meticillin-resistant Staphylococcus aureus ST121, Europe, 2014 to 2024. Autores: Roer L, Yin N, Denis O, Vendrik KE, Zwittink RD, Notermans DW, Perrin M, Khonyongwa K, Tristan A, Youenou B, Layer-Nicolaou F, Werner G, Enger H, Eikrem ECH, Darenberg J, Mäkitalo B, Paulsson M, Björkman J, Fang H, Hallbäck ET, Sundqvist M, Lindholm L, Moganeradj K, García-Cobos S, Cañada-García JE, Holzknecht BJ, Eriksen HB, Hoppe M, Bartels MD, Samaniego Castruita JA, Urth TR, Larsen AR, Petersen A. Revista: Euro Surveill. 2025 Jul;30(28):2500452.

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

Epidemiology, molecular characterisation and antimicrobial susceptibility of Neisseria gonorrhoeae isolates in Madrid, Spain, in 2016

María D. Guerrero-Torres, María B. Menéndez, Carmen S. Guerras, Estela Tello, Juan Ballesteros, Petunia Clavo, Teresa Puerta, Mar Vera, Oskar Ayerdi, Juan C. Carrio, Inmaculada Monzo, Jorge del Romero, Julio A. Vázquez, Raquel Abad. 20. María D. Guerrero-Torres, María B. Menéndez, Carmen S. Guerras, Estela Tello, Juan Ballesteros, Petunia Clavo, Teresa Puerta, Mar Vera, Oskar Ayerdi, Juan C. Carrio, Inmaculada Monzo, Jorge del Romero, Julio A. Vázquez, Raquel Abad. Epidemiol Infect. 2019 Sep 24;147:e274

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 .