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Investigation

Antibiotic Resistance

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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Isolation of Functional SARS-CoV-2 Antigen-Specific T-Cells with Specific Viral Cytotoxic Activity for Adoptive Therapy of COVID-19. García-Ríos, E.; Leivas, A.; Mancebo, F.J.; Sánchez-Vega, L.; Lanzarot, D.; Aguado, J.M.; Martínez-López, J.; Paciello, M.L.; Pérez-Romero, P. Biomedicines 2022, 10, 630. doi: 10.3390/biomedicines10030630.

Isolation of Functional SARS-CoV-2 Antigen-Specific T-Cells with Specific Viral Cytotoxic Activity for Adoptive Therapy of COVID-19. García-Ríos, E.; Leivas, A.; Mancebo, F.J.; Sánchez-Vega, L.; Lanzarot, D.; Aguado, J.M.; Martínez-López, J.; Paciello, M.L.; Pérez-Romero, P. Biomedicines 2022, 10, 630. doi: 10.3390/biomedicines10030630.

Deciphering the Potential Coding of Human Cytomegalovirus: New Predicted Transmembrane Proteome. Mancebo, F.J., Parras-Moltó, M., García-Ríos, E., Pérez-Romero, P. International Journal of Molecular Sciences, 2022, 23(5), 2768. doi: 10.3390/ijms23052768.

Deciphering the Potential Coding of Human Cytomegalovirus: New Predicted Transmembrane Proteome. Mancebo, F.J., Parras-Moltó, M., García-Ríos, E., Pérez-Romero, P. International Journal of Molecular Sciences, 2022, 23(5), 2768. doi: 10.3390/ijms23052768.

Detection of cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance

Cross-Recognition of SARS-CoV-2 B-Cell Epitopes with Other Betacoronavirus Nucleoproteins. Tajuelo, A.; López-Siles, M.; Más, V.; Pérez-Romero, P.; Aguado, J.M.; Briz, V.; McConnell, M.J.; Martín-Galiano, A.J.; López, D. Int. J. Mol. Sci. 2022, 23, 2977. doi: 10.3390/ijms23062977.

PUBMED

Detection of cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance

Immunogenicity of Anti-SARS-CoV-2 Vaccines in Common Variable Immunodeficiency. Arroyo-Sánchez D, Cabrera-Marante O, Laguna-Goya R, Almendro-Vázquez P, Carretero O, Gil-Etayo FJ, Suàrez-Fernández P, Pérez-Romero, P, Rodríguez de Frías E, Serrano A, Allende LM, Pleguezuelo D, Paz-Artal E. J Clin Immunol. 2022 Feb;42(2):240-252. doi: 10.1007/s10875-021-01174-5. PMID: 34787773.

PUBMED

Optimization of a Lambda-RED Recombination Method for Rapid Gene Deletion in Human Cytomegalovirus

Optimization of a Lambda-RED Recombination Method for Rapid Gene Deletion in Human Cytomegalovirus. García-Ríos E, Gata-de-Benito J, López-Siles M, McConnell MJ, Pérez-Romero, P. Int J Mol Sci. 2021 Sep 29;22(19):10558. doi: 10.3390/ijms221910558. PMID: 34638896.

PUBMED

Circulatory follicular helper T lymphocytes associate with lower incidence of CMV infection in kidney transplant recipients

Circulatory follicular helper T lymphocytes associate with lower incidence of CMV infection in kidney transplant recipients. Suàrez-Fernández P, Utrero-Rico A, Sandonis V, García-Ríos E, Arroyo-Sánchez D, Fernández-Ruiz M, Andrés A, Polanco N, González-Cuadrado C, Almendro-Vázquez P, Pérez-Romero P, Aguado JM, Paz-Artal E, Laguna-Goya R. Am J Transplant. 2021 Dec;21(12):3946-3957. doi: 10.1111/ajt.16725. PMID: 34153157.

PUBMED

Is It Feasible to Use CMV-Specific T-Cell Adoptive Transfer as Treatment Against Infection in SOT Recipients?

Is It Feasible to Use CMV-Specific T-Cell Adoptive Transfer as Treatment Against Infection in SOT Recipients? García-Ríos E, Nuévalos M, Mancebo FJ, Pérez-Romero P. Front Immunol. 2021 Apr 23;12:657144. doi: 10.3389/fimmu.2021.657144. PMID: 33968058.

PUBMED

Cytotoxic cell populations developed during treatment with tyrosine kinase inhibitors protect autologous CD4+ T cells from HIV-1 infection

Cytotoxic cell populations developed during treatment with tyrosine kinase inhibitors protect autologous CD4+ T cells from HIV-1 infection. Vigón L, Rodríguez-Mora S, Luna A, Sandonís V, Mateos E, Bautista G, Steegmann JL, Climent N, Plana M, Pérez-Romero P, de Ory F, Alcamí J, García-Gutierrez V, Planelles V, López-Huertas MR, Coiras M. Biochem Pharmacol. 2020 Aug 20;182:114203. doi: 10.1016/j.bcp.2020.114203. PMID: 32828803

PUBMED

Role of Neutralizing Antibodies in CMV Infection: Implications for New Therapeutic Approaches

Role of Neutralizing Antibodies in CMV Infection: Implications for New Therapeutic Approaches. Sandonís V, García-Ríos E, McConnell MJ, Pérez-Romero P.Sandonís V, et al. Trends Microbiol. 2020 Nov;28(11):900-912. doi: 10.1016/j.tim.2020.04.003. PMID: 32448762 Review.

PUBMED

Pre-existing Hemagglutinin Stalk Antibodies Correlate with Protection of Lower Respiratory Symptoms in Flu-Infected Transplant Patients

Pre-existing Hemagglutinin Stalk Antibodies Correlate with Protection of Lower Respiratory Symptoms in Flu-Infected Transplant Patients. Aydillo T, Escalera A, Strohmeier S, Aslam S, Sanchez-Cespedes J, Ayllon J, Roca-Oporto C, Pérez-Romero P, Montejo M, Gavalda J, Munoz P, Lopez-Medrano F, Carratala J, Krammer F, García-Sastre A, Cordero E. Cell Rep Med. 2020 Nov 3;1(8):100130. doi: 10.1016/j.xcrm.2020.100130. PMID: 33294855

PUBMED

Effect of Influenza Vaccination Inducing Antibody Mediated Rejection in Solid Organ Transplant Recipients. Cordero E, Bulnes-Ramos A, Aguilar-Guisado M, González Escribano F, Olivas I, Torre-Cisneros J, Gavaldá J, Aydillo T, Moreno A, Montejo M, Fariñas MC, Carratalá J, Muñoz P, Blanes M, Fortún J, Suárez-Benjumea A, López-Medrano F, Roca C, Lara R, Pérez-Romero P. Front Immunol. 2020 Oct 6;11:1917. doi: 10.3389/fimmu.2020.01917. PMID: 33123119

Effect of Influenza Vaccination Inducing Antibody Mediated Rejection in Solid Organ Transplant Recipients. Cordero E, Bulnes-Ramos A, Aguilar-Guisado M, González Escribano F, Olivas I, Torre-Cisneros J, Gavaldá J, Aydillo T, Moreno A, Montejo M, Fariñas MC, Carratalá J, Muñoz P, Blanes M, Fortún J, Suárez-Benjumea A, López-Medrano F, Roca C, Lara R, Pérez-Romero P. Front Immunol. 2020 Oct 6;11:1917. doi: 10.3389/fimmu.2020.01917. PMID: 33123119

Humoral response to natural influenza infection in solid organ transplant recipients

Humoral response to natural influenza infection in solid organ transplant recipients. Hirzel C, Ferreira VH, L'Huillier AG, Hoschler K, Cordero E, Limaye AP, Englund JA, Reid G, Humar A, Kumar D; Influenza in Transplant Study Group.Hirzel C, et al. Am J Transplant. 2019 Aug;19(8):2318-2328. doi: 10.1111/ajt.15296. Epub 2019 Mar 18.Am J Transplant. 2019. PMID: 30748090 Clinical Trial.

PUBMED

A 5-Year Prospective Multicenter Evaluation of Influenza Infection in Transplant Recipients

A 5-Year Prospective Multicenter Evaluation of Influenza Infection in Transplant Recipients. Kumar D, Ferreira VH, Blumberg E, Silveira F, Cordero E, Perez-Romero P, Aydillo T, Danziger-Isakov L, Limaye AP, Carratala J, Munoz P, Montejo M, Lopez-Medrano F, Farinas MC, Gavalda J, Moreno A, Levi M, Fortun J, Torre-Cisneros J, Englund JA, Natori Y, Husain S, Reid G, Sharma TS, Humar A.Kumar D, et al. Clin Infect Dis. 2018 Oct 15;67(9):1322-1329. doi: 10.1093/cid/ciy294.Clin Infect Dis. 2018. PMID: 29635437 Clinical Trial.

PUBMED

Impact of pretransplant CMV-specific T-cell immune response in the control of CMV infection after solid organ transplantation: a prospective cohort study

Impact of pretransplant CMV-specific T-cell immune response in the control of CMV infection after solid organ transplantation: a prospective cohort study. Molina-Ortega A, Martín-Gandul C, Mena-Romo JD, Rodríguez-Hernández MJ, Suñer M, Bernal C, Sánchez M, Sánchez-Céspedes J, Pérez Romero P, Cordero E.Molina-Ortega A, et al. Clin Microbiol Infect. 2019 Jun;25(6):753-758. doi: 10.1016/j.cmi.2018.09.019. PMID: 30292792 Clinical Trial.

PUBMED

Two Doses of Inactivated Influenza Vaccine Improve Immune Response in Solid Organ Transplant Recipients: Results of TRANSGRIPE 1-2, a Randomized Controlled Clinical Trial.

Two Doses of Inactivated Influenza Vaccine Improve Immune Response in Solid Organ Transplant Recipients: Results of TRANSGRIPE 1-2, a Randomized Controlled Clinical Trial. Cordero E, Roca-Oporto C, Bulnes-Ramos A, Aydillo T, Gavaldà J, Moreno A, Torre-Cisneros J, Montejo JM, Fortun J, Muñoz P, Sabé N, Fariñas MC, Blanes-Julia M, López-Medrano F, Suárez-Benjumea A, Martinez-Atienza J, Rosso-Fernández C, Pérez-Romero P. Clin Infect Dis. 2017 Apr 1;64(7):829-838. doi: 10.1093/cid/ciw855.Clin Infect Dis. 2017. PMID: 28362949 Clinical Trial.

PUBMED

Use of antibodies neutralizing epithelial cell infection to diagnose patients at risk for CMV Disease after transplantation

Use of antibodies neutralizing epithelial cell infection to diagnose patients at risk for CMV Disease after transplantation. Blanco-Lobo P, Cordero E, Martín-Gandul C, Gentil MA, Suárez-Artacho G, Sobrino M, Aznar J, Pérez-Romero P.Blanco-Lobo P, et al. J Infect. 2016 May;72(5):597-607. doi: 10.1016/j.jinf.2016.02.008. Epub 2016 Feb 24.J Infect. 2016. PMID: 26920791 Clinical Trial.

PUBMED

Identification and Analysis of Unstructured, Linear B-Cell Epitopes in SARS-CoV-2 Virion Proteins for Vaccine Development

Identification and Analysis of Unstructured, Linear B-Cell Epitopes in SARS-CoV-2 Virion Proteins for Vaccine Development. Corral-Lugo A, López-Siles M, López D, McConnell MJ, Martin-Galiano AJ. Vaccines. 2020 Jul 20;8(3):397. doi: 10.3390/vaccines8030397.

PUBMED

Using Omics Technologies and Systems Biology to Identify Epitope Targets for the Development of Monoclonal Antibodies Against Antibiotic-Resistant Bacteria

Using Omics Technologies and Systems Biology to Identify Epitope Targets for the Development of Monoclonal Antibodies Against Antibiotic-Resistant Bacteria. Martín-Galiano AJ, McConnell MJ.Front Immunol. 2019 Dec 10;10:2841. doi: 10.3389/fimmu.2019.02841. eCollection 2019.

PUBMED

A lipopolysaccharide-free outer membrane vesicle vaccine protects against Acinetobacter baumannii infection

A lipopolysaccharide-free outer membrane vesicle vaccine protects against Acinetobacter baumannii infection. Pulido MR, García-Quintanilla M, Pachón J, McConnell MJ.Vaccine. 2020 Jan 22;38(4):719-724. doi: 10.1016/j.vaccine.2019.11.043.

PUBMED

A Live Salmonella Vaccine Delivering PcrV through the Type III Secretion System Protects against Pseudomonas aeruginosa.

A Live Salmonella Vaccine Delivering PcrV through the Type III Secretion System Protects against Pseudomonas aeruginosa. Aguilera-Herce J, García-Quintanilla M, Romero-Flores R, McConnell MJ, Ramos-Morales F. mSphere. 2019 Apr 17;4(2):e00116-19. doi: 10.1128/mSphere.00116-19.

PUBMED

Content with Investigacion Inmunopatología del SIDA .

List of staff

Additional Information

Our general objective is to provide early knowledge about any emerging antibiotic resistance mechanism in our country. This contribution of knowledge is based on transversal objectives that we consider key, such as 1) the ability to adapt research to emerging resistance problems, 2) the promotion of cooperative and multidisciplinary research studies working in networks with different Spanish and foreign centers, 3) the transfer of research results in an agile way to the clinical practice of the national health system, and 4) the promotion of the interrelation of research with reference, advice, training and dissemination seeking the empowerment of all. 

More specifically, our main scientific objectives are the characterization of the molecular bases of antibiotic resistance in pathogenic bacteria, the study of the molecular epidemiology and population structure of resistant bacteria, the characterization of the mobile genetic elements that carry resistance genes, and the development of diagnostic techniques and therapeutic alternatives against bacteria with extensive resistance to antibiotics. In this sense, research into the dissemination pathways of Enterobacteriaceae, Acinetobacter baumannii and carbapenemase-producing Pseudomonas aeruginosa (as a paradigm of extensive resistance and pan-resistance) is one of our current priority objectives.

Our general objective is to provide early knowledge about any emerging antibiotic resistance mechanism in our country. This contribution of knowledge is based on transversal objectives that we consider key, such as 1) the ability to adapt research to emerging resistance problems, 2) the promotion of cooperative and multidisciplinary research studies working in networks with different Spanish and foreign centers, 3) the transfer of research results in an agile way to the clinical practice of the national health system, and 4) the promotion of the interrelation of research with reference, advice, training and dissemination seeking the empowerment of all. 

More specifically, our main scientific objectives are the characterization of the molecular bases of antibiotic resistance in pathogenic bacteria, the study of the molecular epidemiology and population structure of resistant bacteria, the characterization of the mobile genetic elements that carry resistance genes, and the development of diagnostic techniques and therapeutic alternatives against bacteria with extensive resistance to antibiotics. In this sense, research into the dissemination pathways of Enterobacteriaceae, Acinetobacter baumannii and carbapenemase-producing Pseudomonas aeruginosa (as a paradigm of extensive resistance and pan-resistance) is one of our current priority objectives.

Content with Investigacion Inmunopatología del SIDA .