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Investigation
Organ Transplant
Research Lines
Content with Investigacion .
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 .
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
Alcazar-Fuoli L, Clavaud C, Lamarre C, Aimanianda V, Seidl-Seiboth V, Mellado E, Latgé JP. Functional analysis of the fungal/plant class chitinase family in Aspergillus fumigatus.
Alcazar-Fuoli L, Clavaud C, Lamarre C, Aimanianda V, Seidl-Seiboth V, Mellado E, Latgé JP. Functional analysis of the fungal/plant class chitinase family in Aspergillus fumigatus. Fungal Genet Biol. 2011 Apr;48(4):418-29. doi: 10.1016/j.fgb.2010.12.007. Epub 2010 Dec 22. PMID: 21184840.
PUBMED DOIImpact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study.
Jiménez-Sousa MA (AC); Gómez-Moreno AZ; Pineda-Tenor D; et al. (1/9) Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study. Biomolecules 2019; 9(4).
DBP rs16846876 and rs12512631 polymorphisms are associated with progression to AIDS naïve HIV-infected patients: a retrospective study.
Jiménez-Sousa MA (AC); Jiménez JL; Fernández-Rodríguez A; et al. (1/10). DBP rs16846876 and rs12512631 polymorphisms are associated with progression to AIDS naïve HIV-infected patients: a retrospective study. Journal of Biomedical Science. 2019; 23;26(1):83. doi: 10.1186/s12929-019-0577-y.
TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients.Journal of Clinical Medicine.
Resino S; Fernández-Rodríguez A; Pineda-Tenor D; et al; Jiménez-Sousa MA. (11/11). 2021. TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients.Journal of Clinical Medicine. 10-3, pp.483. ISSN 2077-0383. https://doi.org/10.3390/jcm10030483.
Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV-coinfected and HCV-monoinfected patients
Salguero, Sergio; Rojo, David; Berenguer, Juan; et al; Jimenez-Sousa, Maria A. (AC) (15/15). 2020. Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV-coinfected and HCV-monoinfected patients LIVER INTERNATIONAL. 40-9, pp.2215-2227. ISSN 1478-3223. https://doi.org/10.1111/liv.14580 3
Telomere Length Increase in HIV/HCV-Coinfected Patients with Cirrhosis after HCV Eradication with Direct-Acting Antivirals JOURNAL OF CLINICAL MEDICINE.
Molina-Carrion, Silvia; Brochado-Kith, Oscar; Gonzalez-Garcia, Juan; et al; Jimenez-Sousa, Maria Angeles. (12/12). 2020. Telomere Length Increase in HIV/HCV-Coinfected Patients with Cirrhosis after HCV Eradication with Direct-Acting Antivirals JOURNAL OF CLINICAL MEDICINE. 9. ISSN 2077-0383. https://doi.org/10.3390/jcm9082407.
Treatment of Chronic Pulmonary Aspergillosis: Current Standards and Future Perspectives. Respiration. 2018 Jul
Alastruey-Izquierdo A, Cadranel J, Flick H, Godet C, Hennequin C, Hoenigl M, Kosmidis C, Lange C, Munteanu O, Page I, Salzer HJF; on behalf of CPAnet. Treatment of Chronic Pulmonary Aspergillosis: Current Standards and Future Perspectives. Respiration. 2018 Jul 6:1-12. doi: 10.1159/000489474. [Epub ahead of print] Review. PMID: 29982245.
PUBMED DOIThe Diagnostic Laboratory Hub: A New Health Care System Reveals the Incidence and Mortality of Tuberculosis, Histoplasmosis, and Cryptococcosis of PWH in Guatemala. Open Forum Infect Dis. 2019 Dec
Samayoa B, Aguirre L, Bonilla O, Medina N, Lau-Bonilla D, Mercado D, Moller A, Perez JC, Alastruey-Izquierdo A, Arathoon E, Denning DW, Rodríguez-Tudela JL; “Fungired”. The Diagnostic Laboratory Hub: A New Health Care System Reveals the Incidence and Mortality of Tuberculosis, Histoplasmosis, and Cryptococcosis of PWH in Guatemala. Open Forum Infect Dis. 2019 Dec 15;7(1):ofz534. doi: 10.1093/ofid/ofz534. PMID: 31915715.
PUBMED DOIFungired. Comparative performance of the laboratory assays used by a Diagnostic Laboratory Hub for opportunistic infections in people living with HIV. AIDS. 2020 Sep 1
Medina N, Alastruey-Izquierdo A, Mercado D, Bonilla O, Pérez JC, Aguirre L, Samayoa B, Arathoon E, Denning DW, Rodriguez-Tudela JL; Fungired. Comparative performance of the laboratory assays used by a Diagnostic Laboratory Hub for opportunistic infections in people living with HIV. AIDS. 2020 Sep 1;34(11):1625-1632. doi: 10.1097/QAD.0000000000002631. PMID: 32694415.
PUBMED DOIPopulation-Based Program of filamentous fungi and Antifungal Resistance in Spain (FILPOP STUDY). Antimicrob Agents Chemother. 2013 Jul
Ana Alastruey-Izquierdo*, Emilia Mellado, Teresa Pelaez, Javier Pemán, Soledad Zapico, María Álvarez, Juan L Rodriguez-Tudela, Manuel Cuenca-Estrella Population-Based Program of filamentous fungi and Antifungal Resistance in Spain (FILPOP STUDY). Antimicrob Agents Chemother. 2013 Jul;57(7):3380-7. doi: 10.1128/AAC.01287-13. PMID: 28319466
PUBMED DOIThe global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet Infect Dis. 2017 Dec
Perlin DS, Rautemaa-Richardson R, Alastruey-Izquierdo A. The global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet Infect Dis. 2017 Dec;17(12. doi: 10.1016/S1473-3099(17)30316-X. PMID: 28774698.
PUBMED DOISequence Analysis of In Vivo-Expressed HIV-1 Spliced RNAs Reveals the Usage of New and Unusual Splice Sites by Viruses of Different Subtypes.
Vega Y, Delgado E, de la Barrera J, Carrera C, Zaballos Á, Cuesta I, Mariño A, Ocampo A, Miralles C, Pérez-Castro S, Álvarez H, López-Miragaya I, García-Bodas E, Díez-Fuertes F, Thomson MM. Sequence Analysis of In Vivo-Expressed HIV-1 Spliced RNAs Reveals the Usage of New and Unusual Splice Sites by Viruses of Different Subtypes. PLoS One. 2016 Jun 29;11(6):e0158525.
PUBMED DOIY155H amino acid substitution in influenza A(H1N1)pdm09 viruses does not confer a phenotype of reduced susceptibility to neuraminidase inhibitors
Perez-Sautu U, Pozo F, Cuesta I, Monzon S, Calderon A, Gonzalez M, Molinero M, Lopez-Miragaya I, Rey S, Cañizares A, Rodriguez G, Gonzalez-Velasco C, Lackenby A, Casas I. Y155H amino acid substitution in influenza A(H1N1)pdm09 viruses does not confer a phenotype of reduced susceptibility to neuraminidase inhibitors. Euro Surveill. 2014 Jul 10;19(27):14-20.
PUBMED DOIComparison of two highly discriminatory typing methods to analyze Aspergillus fumigatus azole resistance
Garcia-Rubio R, Escribano P, Gomez A, Guinea J, and Mellado E. Comparison of two highly discriminatory typing methods to analyze Aspergillus fumigatus azole resistance. Frontiers in Microbiology 2018. Jul 20;9:1626.
PUBMED DOIEvaluation of the possible influence of trailing and paradoxical effects on the clinical outcome of patients with candidemia.
Rueda C, Puig-Asensio M, Guinea J, Almirante B, Cuenca-Estrella M, Zaragoza O. Evaluation of the possible influence of trailing and paradoxical effects on the clinical outcome of patients with candidemia. CANDIPOP Project from GEIH-GEMICOMED (SEIMC) and REIPI. Clin Microbiol Infect. 2017 Jan; 23(1):49.e1-49.e8.
PUBMED DOIDevelopment and Validation of a High-Resolution Melting Assay To Detect Azole Resistance in Aspergillus fumigatus.
Bernal-Martínez L, Gil H, Rivero-Menéndez O, Gago S, Cuenca-Estrella M, Mellado E, Alastruey-Izquierdo A. Development and Validation of a High-Resolution Melting Assay To Detect Azole Resistance in Aspergillus fumigatus. Antimicrob Agents Chemother. 2017 Nov 22;61(12). pii: e01083-17.
PUBMED DOICervicofacial lymphadenitis due Mycobacterium mantenii: rapid and reliable identification by MALDI-TOF MS.
Nebreda T, Andres AG, Fuentes S, Calleja R, Jimenez MS. Cervicofacial lymphadenitis due Mycobacterium mantenii: rapid and reliable identification by MALDI-TOF MS. New Microbes and New Infections .2018. March 22:1-3.
PUBMED DOIIn-depth analysis of the genome sequence of a clinical, extensively drug-resistant Mycobacterium bovis strain.
Sagasta S, Millan-Lou MI, Jiménez MS, Martin C, Samper S. In-depth analysis of the genome sequence of a clinical, extensively drug-resistant Mycobacterium bovis strain. Tuberculosis. 2016. Sep. 100:46-52.
PUBMED DOIGeneration and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection
Detalle L, Stohr T, Palomo C, Piedra PA, Gilbert BE, Mas V, et al. Generation and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection. Antimicrob Agents Chemother. 2016;60(1):6-13.
PUBMED DOIAdditional Information
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).