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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
Off-label use of maraviroc in HIV-1-infected paediatric patients in clinical practice.
Palladino C, Navarro Gomez ML, Soler-Palacin P, Gonzalez-Tome MI, Jiménez de Ory S, Espiau M, Pérez-Hoyos S, León-Leal JA, Méndez M, Moreno-Pérez D, Fortuny C, uer A, Pocheville I, Moreno S, Briz V, on behalf of the CoRISpe Working Group. Off-label use of maraviroc in HIV-1-infected paediatric patients in clinical practice. AIDS 2015; 29-16, pp.2155-2159. (A; FI= 4,407; Q1 Infectious Disease).
PUBMED DOIComparative sensitivity of commercial tests for hepatitis E genotype 3 virus antibody detection.
Comparative sensitivity of commercial tests for hepatitis E genotype 3 virus antibody detection. Avellon A, Morago L, Garcia-Galera del Carmen M, Munoz M, Echevarría JM. J Med Virol. 2015 Nov;87(11):1934-9. Epub 2015 May 29.
PUBMED DOIRelative telomere length impact on mortality of COVID-19: sex differences.
Virseda-Berdices A, Concostrina-Martinez L, Martínez-González O, Blancas R, Resino S, Ryan P, De Juan C, Moreira-Escriche P, Martin-Vicente M, Brochado-Kith O, Blanca-López N, Jiménez-Sousa MA (‡,*), Fernández-Rodríguez A (‡). Relative telomere length impact on mortality of COVID-19: sex differences. J Med Virol 2023; 98 (1): e28368 (A; FI= 20.96; D1, Virology; JCR 2021).
PUBMEDActivity of host antimicrobials against multidrug resistant Acinetobacter baumannii acquiring colistin resistance through loss of lipopolysaccharide
García-Quintanilla, M., Pulido, M. R., Moreno-Martínez, P., Martín-Peña, R., López-Rojas, R., Pachón, J. and McConnell, M.J.* Activity of host antimicrobials against multidrug resistant Acinetobacter baumannii acquiring colistin resistance through loss of lipopolysaccharide. Antimicrobial Agents and Chemotherapy 2014. May;58(5):2972-5.
PUBMED DOICharacterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors
Characterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors. González N, McKee K, Lynch RM, Georgiev IS, Jimenez L, Grau E, Yuste E, Kwong PD, Mascola JR, Alcamí J. PLoS One. 2018;13:e0193773.
PUBMED DOIDiverse large HIV-1 non-subtype B clusters are spreading among men who have sex with men in Spain
Delgado E, Benito S, Montero V, Cuevas MT, Fernández-García A, Sánchez-Martínez M, García-Bodas E, Díez-Fuertes F, Gil H, Cañada J, Carrera C, Martínez-López J, Sintes M, Pérez-Álvarez L, Thomson MM; Spanish Group for the Study of New HIV Diagnoses. Diverse large HIV-1 non-subtype B clusters are spreading among men who have sex with men in Spain. Front Microbiol. 2019; 3;10:655.
PUBMED DOIImprovement of HIV-1 coreceptor tropism prediction by employing selected nucleotide positions of the env gene in a Bayesian network classifier.
Díez-Fuertes F, Delgado E, Vega Y, Fernández-García A, Cuevas MT, Pinilla M, García V, Pérez-Álvarez L, Thomson MM. Improvement of HIV-1 coreceptor tropism prediction by employing selected nucleotide positions of the env gene in a Bayesian network classifier. J Antimicrob Chemother. 2013; 68:1471-1485.
PUBMED DOIPredominance of CXCR4 tropism in HIV-1 CRF14_BG strains from newly diagnosed infections.
Pérez-Álvarez L, Delgado E, Vega Y, Montero V, Cuevas T, Fernández-García A, García-Riart B, Pérez-Castro S, Rodríguez-Real R, López-Álvarez MJ, Fernández-Rodríguez R, Lezaun MJ, Ordóñez P, Ramos C, Bereciartua E, Calleja S, Sánchez-García AM, Thomson MM. Predominance of CXCR4 tropism in HIV-1 CRF14_BG strains from newly diagnosed infections. J Antimicrob Chemother. 2014; 69:246-253.
PUBMED DOIMolecular epidemiology, phylogeny, and phylodynamics of CRF63_02A1, a recently originated HIV-1 circulating recombinant form spreading in Siberia.
Shcherbakova NS, Shalamova LA, Delgado E, Fernández-García A, Vega Y, Karpenko LI, Ilyichev AA, Sokolov YV, Shcherbakov DN, Pérez-Álvarez L, Thomson MM. Molecular epidemiology, phylogeny, and phylodynamics of CRF63_02A1, a recently originated HIV-1 circulating recombinant form spreading in Siberia. AIDS Res Hum Retroviruses. 2014; 30:912-919.
PUBMED DOIEpidemiological surveillance of HIV-1 transmitted drug resistance in Spain in 2004-2012: relevance of transmission clusters in the propagation of resistance mutations.
Vega Y, Delgado E, Fernández-García A, Cuevas MT, Thomson MM, Montero V, Sánchez M, Sánchez AM, Pérez-Álvarez L; Spanish Group for the Study of New HIV-1 Diagnoses in Galicia and Basque Country. Epidemiological surveillance of HIV-1 transmitted drug resistance in Spain in 2004-2012: relevance of transmission clusters in the propagation of resistance mutations. PLoS One. 2015; 10:e0125699.
PUBMED DOIPhylogeny and phylogeography of a recent HIV-1 subtype F outbreak among men who have sex with men in Spain deriving from a cluster with a wide geographic circulation in Western Europe.
Delgado E, Cuevas MT, Domínguez F, Vega Y, Cabello M, Fernández-García A, Pérez-Losada M, Castro MÁ, Montero V, Sánchez M, Mariño A, Álvarez H, Ordóñez P, Ocampo A, Miralles C, Pérez-Castro S, López-Álvarez MJ, Rodríguez R, Trigo M, Diz-Arén J, Hinojosa C, Bachiller P, Hernáez-Crespo S, Cisterna R, Garduño E, Pérez-Álvarez L, Thomson MM. Phylogeny and phylogeography of a recent HIV-1 subtype F outbreak among men who have sex with men in Spain deriving from a cluster with a wide geographic circulation in Western Europe. PLoS One. 2015; 10:e0143325.
PUBMED DOIIdentification of an HIV-1 BG intersubtype recombinant form (CRF73_BG), partially related to CRF14_BG, which Is circulating in Portugal and Spain.
Fernández-García A, Delgado E, Cuevas MT, Vega Y, Montero V, Sánchez M, Carrera C, López-Álvarez MJ, Miralles C, Pérez-Castro S, Cilla G, Hinojosa C, Pérez-Álvarez L, Thomson MM. Identification of an HIV-1 BG intersubtype recombinant form (CRF73_BG), partially related to CRF14_BG, which Is circulating in Portugal and Spain. PLoS One. 2016; 11:e0148549.
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; 11:e0158525.
PUBMED DOIHIV-1 genetic diversity in recently diagnosed infections in Moscow: predominance of AFSU, frequent branching in clusters, and circulation of the Iberian subtype G variant.
Karamov E, Epremyan K, Siniavin A, Zhernov Y, Cuevas MT, Delgado E, Sánchez-Martínez M, Carrera C, Kornilaeva G, Turgiev A, Bacqué J, Pérez-Álvarez L, Thomson MM. HIV-1 genetic diversity in recently diagnosed infections in Moscow: predominance of AFSU, frequent branching in clusters, and circulation of the Iberian subtype G variant. AIDS Res Hum Retroviruses. 2018; 34:629-634.
PUBMED DOIBayesian phylogeographic analyses clarify the origin of the HIV-1 subtype A variant circulating in former Soviet Union's countries.
Díez-Fuertes F, Cabello M, Thomson MM. Bayesian phylogeographic analyses clarify the origin of the HIV-1 subtype A variant circulating in former Soviet Union's countries. Infect Genet Evol. 2015; 33:197-205.
PUBMED DOIAlcazar-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
Additional 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).