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Investigation
Pneumococcus
Research Lines
Content with Investigacion .
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 .
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
Botulism in Spain: Epidemiology and Outcomes of Antitoxin Treatment, 1997-2019
Peñuelas M, Guerrero-Vadillo M, Valdezate S, Zamora MJ, Leon-Gomez I, Flores-Cuéllar Á, Carrasco G, Díaz-García O, Varela C. (2022). Botulism in Spain: Epidemiology and Outcomes of Antitoxin Treatment, 1997-2019. Toxins (Basel). 20;15(1):2
PUBMED DOIInvasive Streptococcus pyogenes disease in Spain: a microbiological and epidemiological study covering the period 2007-2019
Villalón P, Sáez-Nieto JA, Rubio-López V, Medina-Pascual MJ, Garrido N, Carrasco G, Pino-Rosa S, Valdezate S. (2021). Invasive Streptococcus pyogenes disease in Spain: a microbiological and epidemiological study covering the period 2007-2019. Eur J Clin Microbiol Infect Dis. 2021 Nov;40(11):2295-2303
PUBMED DOIRevisiting the Ancylostoma caninum secretome provides new information on hookworm-host interactions.
Morante T, Shepherd C, Constantinoiu C, Loukas A, Sotillo J. Revisiting the Ancylostoma caninum secretome provides new information on hookworm-host interactions. Proteomics. 2017 Dec;17(23-24).
PUBMED DOIHookworm secreted extracellular vesicles interact with host cells and prevent inducible colitis in mice.
Eichenberger RM, Ryan S, Jones L, Buitrago G, Polster R, Montes de Oca M, Zuvelek J, Giacomin PR, Dent LA, Engwerda CR, Field MA, Sotillo J, Loukas A. Hookworm secreted extracellular vesicles interact with host cells and prevent inducible colitis in mice. Front Immunol. 2018 Apr 30;9:850.
PUBMED DOIHDP2: a ribosomal DNA (NTS-ETS) sequence as a target for species-specific molecular diagnosis of intestinal taeniasis in humans.
Flores MD, Gonzalez LM, Hurtado C, Motta YM, Domínguez-Hidalgo C, Merino FJ, Perteguer MJ, Gárate T. HDP2: a ribosomal DNA (NTS-ETS) sequence as a target for species-specific molecular diagnosis of intestinal taeniasis in humans. Parasit Vectors. 2018 Feb 27;11(1):117. doi: 10.1186/s13071-018-2646-6.
PUBMED DOIAntibody responses to chimeric peptides derived from parasite antigens in mice and other animal species.
Orbegozo-Medina RA, Martínez-Sernández V, Folgueira I, Mezo M, González-Warleta M, Perteguer MJ, Romarís F, Leiro JM, Ubeira FM. Antibody responses to chimeric peptides derived from parasite antigens in mice and other animal species. Mol Immunol. 2018 Dec 17;106:1-11.
PUBMED DOIComparison of T24H-his, GST-T24H and GST-Ts8B2 recombinant antigens in western blot, ELISA and multiplex bead-based assay for diagnosis of neurocysticercosis.
Hernández-González A, Noh J, Perteguer MJ, Gárate T, Handali S. Comparison of T24H-his, GST-T24H and GST-Ts8B2 recombinant antigens in western blot, ELISA and multiplex bead-based assay for diagnosis of neurocysticercosis. Parasit Vectors. 2017 May 15;10(1):237.
PUBMED DOICharacterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host-parasite communication.
Eichenberger RM, Talukder MH, Field MA, Wangchuk P, Giacomin P, Loukas A, Sotillo J. Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host-parasite communication. J Extracell Vesicles. 2018 Jan 21;7(1):1428004.
PUBMED DOIEvaluation of onchocerciasis seroprevalence in Bioko Island (Equatorial Guinea) after years of disease control programmes.
Hernández-González A, Moya L, Perteguer MJ, Herrador Z, Nguema R, Nguema J, Aparicio P, Benito A, Gárate T. Evaluation of onchocerciasis seroprevalence in Bioko Island (Equatorial Guinea) after years of disease control programmes. Parasit Vectors. 2016 Sep 20;9(1):509.
PUBMED DOIChanges in protein expression after treatment with Ancylostoma caninum excretory/secretory products in a mouse model of colitis.
Sotillo J, Ferreira I, Potriquet J, Laha T, Navarro S, Loukas A, Mulvenna J. Changes in protein expression after treatment with Ancylostoma caninum excretory/secretory products in a mouse model of colitis. Sci Rep. 2017 Feb 13;7:41883.
PUBMED DOIFasciola spp: Mapping of the MF6 epitope and antigenic analysis of the MF6p/HDM family of heme-binding proteins.
Martínez-Sernández V, Perteguer MJ, Mezo M, González-Warleta M, Gárate T, Valero MA, Ubeira FM. Fasciola spp: Mapping of the MF6 epitope and antigenic analysis of the MF6p/HDM family of heme-binding proteins. PLoS One. 2017 Nov 21;12(11):e0188520.
PUBMED DOIAn alternative host model of a mixed fungal infection by azole susceptible and resistant Aspergillus spp strains
15. Alcazar-Fuoli L, Buitrago M, Gomez-Lopez A, Mellado E. An alternative host model of a mixed fungal infection by azole susceptible and resistant Aspergillus spp strains. Virulence. 2015;6(4):376-84. doi: 10.1080/21505594.2015.1025192. PMID: 26065322.
PUBMED DOIEffect of pneumococcal conjugate vaccines and SARS-CoV-2 on antimicrobial resistance and the emergence of Streptococcus pneumoniae serotypes with reduced susceptibility in Spain, 2004-20: a national surveillance study
Sempere J, Llamosí M, López Ruiz B, Del Río I, Pérez-García C, Lago D, Gimeno M, Coronel P, González-Camacho F, Domenech M, Yuste J. Effect of pneumococcal conjugate vaccines and SARS-CoV-2 on antimicrobial resistance and the emergence of Streptococcus pneumoniae serotypes with reduced susceptibility in Spain, 2004-20: a national surveillance study. Lancet Microbe. 2022 Oct;3(10):e744-e752.
PUBMED DOISeconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains
Tirado-Vélez JM, Carreño D, Sevillano D, Alou L, Yuste J, de la Campa AG. Seconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains. Antibiotics. 2021 May 13;10(5):573.
PUBMED DOIMinilungs from Human Embryonic Stem Cells to Study the Interaction of Streptococcus pneumoniae with the Respiratory Tract
Sempere J, Rossi SA, Chamorro-Herrero I, González-Camacho F, de Lucas MP, Rojas-Cabañeros JM, Taborda CP, Zaragoza Ó, Yuste J, Zambrano A. Minilungs from Human Embryonic Stem Cells to Study the Interaction of Streptococcus pneumoniae with the Respiratory Tract. Microbiol Spectr. 2022 Jun 29;10(3):e0045322
PUBMED DOIA national longitudinal study evaluating the activity of cefditoren and other antibiotics against non-susceptible Streptococcus pneumoniae strains during the period 2004-20 in Spain
Sempere J, González-Camacho F, Domenech M, Llamosí M, Del Río I, López-Ruiz B, Gimeno M, Coronel P, Yuste J. A national longitudinal study evaluating the activity of cefditoren and other antibiotics against non-susceptible Streptococcus pneumoniae strains during the period 2004-20 in Spain. J Antimicrob Chemother. 2022 Mar 31;77(4):1045-1051.
PUBMED DOINationwide Trends of Invasive Pneumococcal Disease in Spain From 2009 Through 2019 in Children and Adults During the Pneumococcal Conjugate Vaccine Era
de Miguel S, Domenech M, González-Camacho F, Sempere J, Vicioso D, Sanz JC, Comas LG, Ardanuy C, Fenoll A, Yuste J. Nationwide Trends of Invasive Pneumococcal Disease in Spain From 2009 Through 2019 in Children and Adults During the Pneumococcal Conjugate Vaccine Era. Clin Infect Dis. 2021 Dec 6;73(11):e3778-e3787
PUBMED DOIPulmonary BCG induces lung-resident macrophage activation and confers long-term protection against tuberculosis
7. Mata E, Tarancón R, Guerrero C, Moreo E, Moreau F, Uranga S, Gomez AB, Marinova D, Domenech M, Gonzalez-Camacho F, Monzon M, Badiola J, Dominguez-Andres J, Yuste J, Anel A, Peixoto A, Martin C, Aguilo N. Pulmonary BCG induces lung-resident macrophage activation and confers long-term protection against tuberculosis. Sci Immunol. 2021 Sep 24;6(63):eabc2934
PUBMED DOIAdditional 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.