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Research Lines

Content with Investigacion Neisseria, Listeria y Bordetella .

Neisseria, Listeria y Bordetella

• Invasive Meningococcal Disease.

o Laboratory surveillance based on whole-genome sequencing and its application in Public Health.

o Study and characterization of antimicrobial resistance mechanisms.

o Study and evaluation of conventional (polysaccharide) and new-generation (protein) vaccines.

• Gonococcal Infection (Gonorrhea).

o Laboratory surveillance based on whole-genome sequencing and its application in Public Health.

o Study and characterization of antimicrobial resistance mechanisms.

• Listeriosis.

o Laboratory surveillance based on whole-genome sequencing and its application in Public Health.

• Pertussis.

o Development and application of molecular techniques for the diagnosis and characterization of Bordetella pertussis, B. parapertussis, B. holmessi, and B. bronchiseptica.

Research projects

Content with Investigacion Neisseria, Listeria y Bordetella .

1. Project Title: Determination of the degree of identity of common antigens of N. meningitidis and N. gonorrhoeae using genomic and immunological tools.
Principal Investigator: Raquel Abad Torreblanca
Funding Entity: ISCIII. Program: Strategic Action in Intramural Health
Reference: PI23CIII/00040
Period: 2024-2026
Amount Awarded: €68,500

2. Project Title: Meningococcal Disease and Molecular Epidemiology (MEMORY).
Principal Investigator: Raquel Abad Torreblanca and Julio A. Vázquez Moreno
Funding Entity: Pfizer Inc.
Reference: MVP 352/21
Period: 2022-2024
Amount Awarded: €82,834.50

3. Project Title: Modelling Approaches to Guide Intelligent Surveillance for the Sustainable Introduction of Novel Antibiotics. MAGIcIAN.
Principal Investigator: Raquel Abad Torreblanca
Funding Entity: ISCIII / International Joint Action / Joint Programming Initiatives (JPI) Program
Reference: AC19CIII/00002
Period: 2020-2024
Amount Awarded: €46,000

4. Project Title: Epidemiological, Microbiological, and Clinical Analysis of the Listeriosis Outbreak in Andalusia. LISMOAN Study.
Principal Investigator: José Miguel Cisneros Herreros
Funding Entity: FISEVI (Andalusian Public Foundation for Health Research Management)/FPS2020 Call for Proposals
Reference: PI-0001-2020
Period: 2020-2023
Amount Awarded: €114,954

5. Project Title: Population Structure of Neisseria meningitidis Using Massive Sequencing: A Potential Tool for Estimating Vaccine Effectiveness?
Principal Investigator: Raquel Abad Torreblanca
Funding Entity: ISCIII / Strategic Action in Intramural Health
Reference: PI19CIII/00030
Period: 2020-2023
Amount Awarded: €67,153

6. Project Title: Management agreement between the Ministry of Health, Social Services and Equality (Directorate General of Public Health, Quality and Innovation) and the Carlos III Health Institute, for the laboratory determinations corresponding to the 2nd seroprevalence study in Spain.
Principal Investigator: Fernando de Ory and Julio A. Vázquez
Funding Entity: Directorate General of Public Health, Ministry of Health
Reference: MEG151/17
Period: 2018-2020
Amount Awarded: €565,663

7. Project Title: Effectiveness of the Meningococcal B Vaccine in Immunocompromised Children with Sickle Cell Disease
Principal Investigator: Raquel Abad Torreblanca
Funding Entity: Spanish Society of Pediatric Hematology and Oncology Foundation (SEHOP)
Reference: MVP 199/18
Period: 2018-2020
Amount Awarded: €18,285

8. Project Title: Application of Massive Sequencing and Immunological Approaches in the Expression Analysis of New Vaccine Antigens in Meningococcal Populations
Principal Investigator: Raquel Abad Torreblanca
Funding Entity: ISCIII / Strategic Action in Intramural Health
Reference: PI16CIII/00023
Period: 2017-2020
Amount Awarded: €115,084

9. Project Title: fHbp variability over time and potential coverage of the new meningococcal serogroup B vaccine (bivalent rLP2086/fHbp) in Spain.
Principal Investigators: Raquel Abad and Julio A. Vázquez
Funding Entity: Pfizer SLU
Reference: MVP 1273/16
Period: 2017-2020
Amount Awarded: €125,350

10. Project Title: Estimation of protection of a conjugate vaccine against meningococcus serogroup C based on a mathematical model.
Principal Investigator: Julio A. Vázquez and Javier Díez
Funding Entity: Higher Center for Research in Public Health (CSISP)
Reference: MVP 1116/11
Period: 2011-2017
Amount awarded: €143,750

Publications

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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 DOI

Invasive 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 DOI

ANISERP: a new serpin from the parasite Anisakis simplex.

Valdivieso E, Perteguer MJ, Hurtado C, Campioli P, Rodríguez E, Saborido A, Martínez-Sernández V, Gómez-Puertas P, Ubeira FM, Gárate T. ANISERP: a new serpin from the parasite Anisakis simplex.Parasit Vectors. 2015 Jul 28;8:399.

PUBMED DOI

Revisiting 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 DOI

Hookworm 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 DOI

HDP2: 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 DOI

Antibody 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 DOI

Comparison 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 DOI

Characterization 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 DOI

Evaluation 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 DOI

Changes 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 DOI

Fasciola 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 DOI

Accumulation of endogenous free radicals is required to induce titan-like cell formation in Cryptococcus neoformans

Irene García-Barbazán, Alba Torres-Cano, Rocío García-Rodas, Martin Sachse, Daniel Luque, Diego Megías, Oscar Zaragoza. mBio. 2024 Jan 16;15(1):e0254923

PUBMED DOI

An 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 DOI

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

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 DOI

Seconeolitsine, 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 DOI

Minilungs 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 DOI

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

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 DOI

Nationwide 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 DOI

Pulmonary 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 DOI

Content with Investigacion Infección Viral e Inmunidad .

List of staff

Additional Information

La inducción de la tolerancia al aloinjerto sigue siendo una meta por alcanzar en el trasplante de órganos. La mayoría de las estrategias terapéuticas se centran en la inhibición del sistema inmunológico adaptativo, pero datos recientes demuestran que el reconocimiento alogénico de las células mieloides inicia el rechazo al trasplante. Terapias dirigidas hacia las células mieloides “in vivo” representan un objetivo potencial para inducir tolerancia inmunológica, pero permanece inexplorado clínicamente.Nuestro laboratorio utiliza una nanoinmunoterapia revolucionaria de nanopartículas de lipoproteínas de alta densidad (HDL) cargadas con rapamicina (mTORi-HDL) que previenen las modificaciones epigenéticas asociadas con la inmunidad entrenada, un estado funcional de los macrófagos recientemente descubierto. Usando un modelo experimental de trasplante en ratón, nuestros resultados demuestran que la administración de esta inmunoterapia con mTORi-HDL previene la respuesta inmunológica y promueve la tolerancia al órgano trasplantado.Nuestro laboratorio muestra un enfoque de investigación multidisciplinar articulado en tres objetivos diferentes para evaluar la relevancia clínica y los efectos terapéuticos de la inmunoterapia como preparación para un ensayo clínico en trasplante de órganos. Los objetivos generales estarán orientados a confirmar la identificación de la inmunidad entrenada como biomarcador y valor analítico para predecir el riesgo de rechazo en pacientes trasplantados bajo tres condiciones: periodos prolongadas de reperfusión isquémica (IRI) (objetivo 1), alosensibilización (objetivo 2) e infección (objetivo 3).

Induction of allograft tolerance remains a goal to be achieved in organ transplantation. Most therapeutic strategies focus on inhibition of the adaptive immune system, but recent data demonstrate that allogeneic recognition of myeloid cells initiates transplant rejection. Therapies targeting myeloid cells “in vivo” represent a potential target to induce immunological tolerance, but remain clinically unexplored. 

Our laboratory uses a revolutionary nanoimmunotherapy of high-density lipoprotein (HDL) nanoparticles loaded with rapamycin (mTORi-HDL) that prevents epigenetic modifications associated with trained immunity, a recently discovered functional state of macrophages. Using an experimental mouse transplant model, our results demonstrate that the administration of this immunotherapy with mTORi-HDL prevents the immune response and promotes tolerance to the transplanted organ. 

Our laboratory shows a multidisciplinary research approach articulated in three different objectives to evaluate the clinical relevance and therapeutic effects of immunotherapy in preparation for a clinical trial in organ transplantation. The general objectives will be aimed at confirming the identification of trained immunity as a biomarker and analytical value to predict the risk of rejection in transplant patients under three conditions: prolonged periods of ischemic reperfusion (IRI) (objective 1), allosensitization (objective 2) and infection (objective 3).

Induction of allograft tolerance remains a goal to be achieved in organ transplantation. Most therapeutic strategies focus on inhibition of the adaptive immune system, but recent data demonstrate that allogeneic recognition of myeloid cells initiates transplant rejection. Therapies targeting myeloid cells “in vivo” represent a potential target to induce immunological tolerance, but remain clinically unexplored. 

Our laboratory uses a revolutionary nanoimmunotherapy of high-density lipoprotein (HDL) nanoparticles loaded with rapamycin (mTORi-HDL) that prevents epigenetic modifications associated with trained immunity, a recently discovered functional state of macrophages. Using an experimental mouse transplant model, our results demonstrate that the administration of this immunotherapy with mTORi-HDL prevents the immune response and promotes tolerance to the transplanted organ. 

Our laboratory shows a multidisciplinary research approach articulated in three different objectives to evaluate the clinical relevance and therapeutic effects of immunotherapy in preparation for a clinical trial in organ transplantation. The general objectives will be aimed at confirming the identification of trained immunity as a biomarker and analytical value to predict the risk of rejection in transplant patients under three conditions: prolonged periods of ischemic reperfusion (IRI) (objective 1), allosensitization (objective 2) and infection (objective 3).

Content with Investigacion Infección Viral e Inmunidad .