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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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CD45 expression discriminates waves of embryonic megakaryocytes in the mouse.

Cortegano, I., Serrano, N., Ruiz, C., Rodríguez, M., Prado, C., Alía, M., Hidalgo, A., Cano, E., de Andrés B. and Gaspar, ML. 2018. Haematologica, 104(9):1853-1865

PUBMED DOI

Hypervirulent Klebsiella pneumoniae: Epidemiology outside Asian countries, antibiotic resistance association, methods of detection and clinical management

12. Hypervirulent Klebsiella pneumoniae: Epidemiology outside Asian countries, antibiotic resistance association, methods of detection and clinical management. Autores: García-Cobos S, Oteo-Iglesias J, Pérez-Vázquez M. Revista: Enferm Infecc Microbiol Clin (Engl Ed). 2025 Feb;43(2):102-109.

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

Listeriosis outbreak caused by contaminated stuffed pork, Andalusia, Spain, July to October 2019

Fernández-Martínez NF, Ruiz-Montero R, Briones E, Baños E, García San Miguel Rodríguez-Alarcón L, Chaves JA, Abad R, Varela C; LISMOAN team; Lorusso N. Euro Surveill . 2022 Oct;27(43):2200279

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

A novel typing method for Streptococcus pneumoniae using selected surface proteins

Domenech A, Moreno J, Ardanuy C, Liñares J, de la Campa AG, Martin-Galiano AJ. Front Microbiol. 2016; 31;7:420.

PUBMED DOI

Podocytes as new cellular targets of hemoglobin toxicity in massive intravascular hemolysis.

Rubio-Navarro A, Sanchez-Niño MD, Guerrero-Hue M, García-Caballero C, Gutiérrez E, Yuste C, Sevillano A, Praga M, Egea J, Román E, Cannata P, Ortega R, Cortegano I, de Andrés B, Gaspar ML, Cadenas S, Ortiz A, Egido J, Moreno JA. Podocytes as new cellular targets of hemoglobin toxicity in massive intravascular hemolysis. 2018. J.Pathol. 244(3):296-310.

PUBMED DOI

Carbapenemase-Producing Klebsiella pneumoniae in COVID-19 Intensive Care Patients: Identification of IncL-VIM-1 Plasmid in Previously Non-Predominant Sequence Types.

13. Carbapenemase-Producing Klebsiella pneumoniae in COVID-19 Intensive Care Patients: Identification of IncL-VIM-1 Plasmid in Previously Non-Predominant Sequence Types. Autores: Cañada-García JE, Ramírez de Arellano E, Jiménez-Orellana M, Viedma E, Sánchez A, Alhambra A, Villa J, Delgado-Iribarren A, Bautista V, Lara N, García-Cobos S, Aracil B, Cercenado E, Pérez-Vázquez M, Oteo-Iglesias J. Revista: Antibiotics (Basel). 2023 Jan 6;12(1):107.

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

Pertactin-Deficient Bordetella pertussis with Unusual Mechanism of Pertactin Disruption, Spain, 1986-2018

14. Mir-Cros A, Moreno-Mingorance A, Martín-Gómez MT, Abad R, Bloise I, Campins M, González-Praetorius A, Gutiérrez MN, Martín-González H, Muñoz-Almagro C, Orellana MÁ, de Pablos M, Roca-Grande J, Rodrigo C, Rodríguez ME, Uriona S, Vidal MJ, Pumarola T, Larrosa MN, González-López JJ. Emerg Infect Dis. 2022 May;28(5):967-976

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

An increase in negative supercoiling in bacteria reveals topology-reacting gene clusters and a homeostatic response mediated by the DNA topoisomerase I gene

Ferrándiz MJ, Martín-Galiano AJ, Arnanz C, Camacho-Soguero I, Tirado-Vélez JM, de la Campa AG. 2016. Nucl Acids Res. 44:7292-7303 (2016).

PUBMED DOI

Spatially-restricted JAG1-Notch signaling in the human thymus provides permissive microenvironments for dendritic cell development.

Martín Gayo, E., González-García, S., García-León, M., Murcia-Ceballos, A., Alcain, J., García-Peydró, M., Allende, L., de Andrés, B., Gaspar, ML. and Toribio, ML. J.Exp.Med. (2017) 214:3361-3379

PUBMED DOI

Carbapenemase-producing Emergence of NDM-producing Klebsiella pneumoniae and Escherichia coli in Spain: phylogeny, resistome, virulence and plasmids encoding blaNDM-like genes as determined by WGS. aeruginosa in Spain: interregional dissemination of the high risk-clones ST175 and ST244 carrying blaVIM-2, blaVIM-1, blaIMP-8, blaVIM-20 and blaKPC-2

14. Emergence of NDM-producing Klebsiella pneumoniae and Escherichia coli in Spain: phylogeny, resistome, virulence and plasmids encoding blaNDM-like genes as determined by WGS. Autores: Pérez-Vázquez M, Sola Campoy PJ, Ortega A, Bautista V, Monzón S, Ruiz-Carrascoso G, Mingorance J, González-Barberá EM, Gimeno C, Aracil B, Sáez D, Lara N, Fernández S, González-López JJ, Campos J, Kingsley RA, Dougan G, Oteo-Iglesias J; Spanish NDM Study Group. Revista: J Antimicrob Chemother. 2019 Dec 1;74(12):3489-3496.

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

Large Increase in Azithromycin-Resistant Neisseria gonorrhoeae in Northern Spain

Carballo R, Povoa MC, Abad R, Navarro C, Martin E, Alvarez M, Salgado A, Potel C. Microb Drug Resist. 2022 Jan;28(1):81-86

PUBMED DOI

Epidemiology of the Acinetobacter-derived cephalosporinase, carbapenem-hydrolysing oxacillinase and metallo-beta-lactamase genes, and of common insertion sequences, in epidemic clones of Acinetobacter baumannii from Spain

Villalón P, Valdezate S, Medina-Pascual MJ, Carrasco G, Vindel A, Saez-Nieto JA. Epidemiology of the Acinetobacter-derived cephalosporinase, carbapenem-hydrolysing oxacillinase and metallo-beta-lactamase genes, and of common insertion sequences, in epidemic clones of Acinetobacter baumannii from Spain. J Antimicrob Chemother. 2013;68(3):550-3.

PUBMED DOI

Reactive oxygen species contribute to the bactericidal effects of the fluoroquinolone moxifloxacin in Streptococcus pneumoniae

Ferrándiz MJ, Martín-Galiano AJ, Arnanz C, Zimmerman T, de la Campa AG. Antimicrob Agents Chemother. 60:409-417 (2016).

PUBMED DOI

Altered Marginal Zone and innate-like B cells in aged SAMP8 mice with defective IgG1 responses

Cortegano, I., Rodriguez, M., Martin, I., Prado, C., Ruiz, C., Hortigüela, R., Alia, M., Vilar, M., Mira, H., Cano, E., de Andrés, B., and Gaspar, ML. Cell death & disease (2017) 8, e3000

PUBMED DOI

Rapid cross-border emergence of NDM-5-producing Escherichia coli in the European Union/European Economic Area, 2012 to June 2022

15. Rapid cross-border emergence of NDM-5-producing Escherichia coli in the European Union/European Economic Area, 2012 to June 2022. Autores: Linkevicius M, Bonnin RA, Alm E, Svartström O, Apfalter P, Hartl R, Hasman H, Roer L, Räisänen K, Dortet L, Pfennigwerth N, Hans JB, Tóth Á, Buzgó L, Cormican M, Delappe N, Monaco M, Giufrè M, Hendrickx AP, Samuelsen Ø, Pöntinen AK, Caniça M, Manageiro V, Oteo-Iglesias J, Pérez-Vázquez M, Westmo K, Mäkitalo B, Palm D, Monnet DL, Kohlenberg A. Revista: Euro Surveill. 2023 May;28(19):2300209.

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 .