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Investigation

AIDS Immunopathology

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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Postnatal and adult immunoglobulin repertoires of innate-like CD19(+)CD45R(lo) B Cells.

Prado, C., Rodriguez, M., Cortegano I., Ruiz, C., Alía, M., de Andrés, B., Gaspar, ML. J Inn Inmmunol. (2014) 6: 499-514

PUBMED DOI

Characterization of Carbapenemase-Producing Klebsiella oxytoca in Spain, 2016-2017.

18. Characterization of Carbapenemase-Producing Klebsiella oxytoca in Spain, 2016-2017. Autores: Pérez-Vazquez M, Oteo-Iglesias J, Sola-Campoy PJ, Carrizo-Manzoni H, Bautista V, Lara N, Aracil B, Alhambra A, Martínez-Martínez L, Campos J; Spanish Antibiotic Resistance Surveillance Program Collaborating Group. Revista: Antimicrob Agents Chemother. 2019 May 24;63(6): e02529-18.

PUBMED DOI

HIV-1-specific CD8+ T cell responses and viral evolution in women and infants

Sanchez-Merino V, Nie S, Luzuriaga K*. 2005. J Immunol 175:6976-86.

PUBMED DOI

The global meningitis genome partnership

Rodgers E, Bentley SD, Borrow R, Bratcher HB, Brisse S, Brueggemann AB, Caugant DA, Findlow J, Fox L, Glennie L, Harrison LH, Harrison OB, Heyderman RS, van Rensburg MJ, Jolley KA, Kwambana-Adams B, Ladhani S, LaForce M, Levin M, Lucidarme J, MacAlasdair N, Maclennan J, Maiden MCJ, Maynard-Smith L, Muzzi A, Oster P, Rodrigues CMC, Ronveaux O, Serino L, Smith V, van der Ende A, Vázquez J, Wang X, Yezli S, Stuart JM. J Infect. 2020; 81(4): 510-520

PUBMED DOI

Notch1 regulates progenitor cell proliferation and differentiation during murine yolk sac hematopoiesis

Isabel Cortegano, Pedro Melgar-Rojas, Luis Luna-Zurita, Miguel Ángel Rodríguez-Marcos, MA., Gaspar ML., and José Luis de la Pompa, JL. Cell death and diff. (2014) 21: 1081-1094

PUBMED DOI

Spread of the FAR-MRSA clone, a fusidic acid- and meticillin-resistant Staphylococcus aureus ST121, Europe, 2014 to 2024.

19. Spread of the FAR-MRSA clone, a fusidic acid- and meticillin-resistant Staphylococcus aureus ST121, Europe, 2014 to 2024. Autores: Roer L, Yin N, Denis O, Vendrik KE, Zwittink RD, Notermans DW, Perrin M, Khonyongwa K, Tristan A, Youenou B, Layer-Nicolaou F, Werner G, Enger H, Eikrem ECH, Darenberg J, Mäkitalo B, Paulsson M, Björkman J, Fang H, Hallbäck ET, Sundqvist M, Lindholm L, Moganeradj K, García-Cobos S, Cañada-García JE, Holzknecht BJ, Eriksen HB, Hoppe M, Bartels MD, Samaniego Castruita JA, Urth TR, Larsen AR, Petersen A. Revista: Euro Surveill. 2025 Jul;30(28):2500452.

DOI

Modulation of Env content in virions of simian immunodeficiency virus: correlation with cell surface expression and virion infectivity

Yuste E, Reeves JD, Doms RW, Desrosiers RC*. 2004. J Virol 78:6775-85.

PUBMED DOI

Epidemiology, molecular characterisation and antimicrobial susceptibility of Neisseria gonorrhoeae isolates in Madrid, Spain, in 2016

María D. Guerrero-Torres, María B. Menéndez, Carmen S. Guerras, Estela Tello, Juan Ballesteros, Petunia Clavo, Teresa Puerta, Mar Vera, Oskar Ayerdi, Juan C. Carrio, Inmaculada Monzo, Jorge del Romero, Julio A. Vázquez, Raquel Abad. 20. María D. Guerrero-Torres, María B. Menéndez, Carmen S. Guerras, Estela Tello, Juan Ballesteros, Petunia Clavo, Teresa Puerta, Mar Vera, Oskar Ayerdi, Juan C. Carrio, Inmaculada Monzo, Jorge del Romero, Julio A. Vázquez, Raquel Abad. Epidemiol Infect. 2019 Sep 24;147:e274

PUBMED DOI

Content with Investigacion Inmunopatología del SIDA .

List of staff

Additional Information

The AIDS Immunopathology Unit has been coordinated since 2000 by Dr. José Alcamí, bringing together during its history more than 20 independent researchers who collaboratively study different aspects of HIV infection. During this years, more than 30 visiting researchers and more than 50 national and international students have passed through the unit. From the beginning of the year 2025, Javier García Pérez and Francisco Díez Fuertes assumed the coordination of the AIDS Immunopathology Unit, with the aim of projecting its scientific competitiveness following multidisciplinary approaches and through the maintenance of the current close collaborations, as well as the promotion of participation in new national and international research networks.
Historically, the current members of the unit have focused on different lines of basic research that include the study of antibodies and the development of vaccines against HIV-1, the study of viral entry and tropism of the virus or the study of the host through the genomic characterization of populations with an extreme phenotype. Currently, the activity of our unit in the field of HIV-1 is focused on three main lines:
1.    Mecanismos moleculares asociados a la protección de la infección por VIH-1 en pacientes con distrofia muscular de cinturas dominante D2 (LGMDD2).
2.    Generación de anticuerpos neutralizantes de uso terapéutico basados en la respuesta neutralizante de amplio espectro frente a virus fundadores.
3.    Cribado y caracterización de nuevos fármacos anti-latencia frente al VIH-1.
A partir del año 2020, nuestra unidad se vuelca con la investigación sobre COVID-19, participando y liderando diferentes proyectos de investigación aplicada y clínica. Fruto de esta fuerte implicación en el campo, en la actualidad se mantienen diferentes estudios sobre la caracterización de la respuesta inmune frente a SARS-CoV-2, integrando diferentes técnicas de virología molecular, estrategias de inteligencia epidemiológica y tecnologías de célula única.
We also participate in different research consortiums and networks, such as the Spanish AIDS Research Network or the Center for Biomedical Research in Infectious Diseases Network (CIBER-INFEC), in which we participate as researchers in different lines and work packages within the research programs “Global Health, emerging and re-emerging infections” as well as “HIV/AIDS and sexually transmitted infections”.


Supervised doctoral theses

1.    GENOMIC AND FUNCTIONAL ANALYSIS OF HIV-1 PROTECTION PARAMETERS IN PATIENTS WITH SLOW PROGRESSION OF INFECTION. 
Student: Erick de la Torre Tarazona.
Supervisors: José Alcamí and Francisco Díez Fuertes.
Academic entity: Universidad Autónoma de Madrid.
Defense date: July 14th, 2020.
2.    ANALYSIS OF MIARN EXPRESSION PROFILES AND FUNCTIONAL CHARACTERIZATION IN HIV-POSITIVE INDIVIDUALS WITH DIFFERENT PROGRESSION TO AIDS.
Student: Rubén Ayala Suárez.
Supervisors: José Alcamí and Francisco Díez Fuertes.
Academic entity: Universidad de Alcalá.
Defense date: June 12nd, 2023.

The AIDS Immunopathology Unit has been coordinated since 2000 by Dr. José Alcamí, bringing together during its history more than 20 independent researchers who collaboratively study different aspects of HIV infection. During this years, more than 30 visiting researchers and more than 50 national and international students have passed through the unit. From the beginning of the year 2025, Javier García Pérez and Francisco Díez Fuertes assumed the coordination of the AIDS Immunopathology Unit, with the aim of projecting its scientific competitiveness following multidisciplinary approaches and through the maintenance of the current close collaborations, as well as the promotion of participation in new national and international research networks.
Historically, the current members of the unit have focused on different lines of basic research that include the study of antibodies and the development of vaccines against HIV-1, the study of viral entry and tropism of the virus or the study of the host through the genomic characterization of populations with an extreme phenotype. Currently, the activity of our unit in the field of HIV-1 is focused on three main lines:
1.    Mecanismos moleculares asociados a la protección de la infección por VIH-1 en pacientes con distrofia muscular de cinturas dominante D2 (LGMDD2).
2.    Generación de anticuerpos neutralizantes de uso terapéutico basados en la respuesta neutralizante de amplio espectro frente a virus fundadores.
3.    Cribado y caracterización de nuevos fármacos anti-latencia frente al VIH-1.
A partir del año 2020, nuestra unidad se vuelca con la investigación sobre COVID-19, participando y liderando diferentes proyectos de investigación aplicada y clínica. Fruto de esta fuerte implicación en el campo, en la actualidad se mantienen diferentes estudios sobre la caracterización de la respuesta inmune frente a SARS-CoV-2, integrando diferentes técnicas de virología molecular, estrategias de inteligencia epidemiológica y tecnologías de célula única.
We also participate in different research consortiums and networks, such as the Spanish AIDS Research Network or the Center for Biomedical Research in Infectious Diseases Network (CIBER-INFEC), in which we participate as researchers in different lines and work packages within the research programs “Global Health, emerging and re-emerging infections” as well as “HIV/AIDS and sexually transmitted infections”.


Supervised doctoral theses

1.    GENOMIC AND FUNCTIONAL ANALYSIS OF HIV-1 PROTECTION PARAMETERS IN PATIENTS WITH SLOW PROGRESSION OF INFECTION. 
Student: Erick de la Torre Tarazona.
Supervisors: José Alcamí and Francisco Díez Fuertes.
Academic entity: Universidad Autónoma de Madrid.
Defense date: July 14th, 2020.
2.    ANALYSIS OF MIARN EXPRESSION PROFILES AND FUNCTIONAL CHARACTERIZATION IN HIV-POSITIVE INDIVIDUALS WITH DIFFERENT PROGRESSION TO AIDS.
Student: Rubén Ayala Suárez.
Supervisors: José Alcamí and Francisco Díez Fuertes.
Academic entity: Universidad de Alcalá.
Defense date: June 12nd, 2023.

The current director of CNM is Dr. José Miguel Rubio Muñoz.

Dr. José Miguel Rubio has a degree in Biological Sciences from the Universidad Autónoma de Madrid (1986) and a PhD in Biological Sciences from the same university (1992). He carried out his doctoral thesis at the Department of Genetics of the Universidad Autónoma de Madrid, as Associate Professor (1988-1989), and at the School of Biology of the University of East Anglia in Norwich, UK, as Senior Research Assistant (1989-1992).

During his postdoctoral period he obtained a grant from the European Commission within the Human Capital and Mobility Program to be carried out at the University of “La Sapienza” in Rome, Italy and the Institute of Molecular Biology and Biotechnology in Crete, Greece (1993-1994). Subsequently, he made a further stay funded by the WHO and the university itself at the Department of Entomology, Wageningen University, The Netherlands (1994-1996).

Since 1997 he has been a member of the Instituto de Salud Carlos III (ISCIII), where he joined the Department of Parasitology of the National Center of Microbiology, as an EU-INCO postdoctoral fellow and later with a grant from the Autonomous Community of Madrid (CAM). She was part of the founding group of the National Center for Tropical Medicine (2003-2006) and of the 24/7 Alerts and Emergencies Unit (2006-2018) and is currently Head of the Malaria and Emerging Parasitosis Unit of the National Microbiology Center and is part, as research staff, of the Center for Biomedical Research Network on Infectious Diseases (CIBERINFEC/ISCIII).

During his scientific career he has been Visiting Scientist at the Leonidas e Marie Dean Center (FIOCRUZ-AMAZONAS, Manaus, Brazil) and is an External Consultant of the Parasitology Departments of Cairo University (Egypt) and the Medical Research Center (MRC) of Kuala Lumpur (Malaysia).  He also belongs or has belonged to different national and international committees:  Member of the expert group for malaria control of the European Centre for Disease Control (ECDC) since 2011; Expert-Evaluator for health programs of the European Commission since 2004; Spanish Representative (commissioned by ISCIII and MSC) in the Technical Scientific Committee of the TDR (WHO) 2007-2008; Spanish Deputy Focal Point for microbiology at the European Centre for Disease Control (ECDC) from 2012 to 2020; and, member of the Research Ethics Committee of ISCIII until 2019.

In this period he has published more than 100 articles in international indexed journals, 10 book chapters and has been co-editor of two books in the area of malaria, tropical medicine and neglected diseases. He has participated in 58 competitively funded research projects, 20 of them international, having been the principal investigator in 8 national and 11 international projects as PI of the project or WP leader. In addition, he has led five agreements with companies. Currently he has been awarded four sexenios of research, being presented this year 2025 to the fifth. In the teaching field, he participates in different postgraduate programs in the areas of microbiology and parasitology, having directed seven doctoral theses and more than 20 Master's or Degree final projects, both nationally and internationally. ​​​​​

El laboratorio de Referencia e Investigación en Resistencia a Antibióticos ofrece una amplia cartera de servicios al Sistema Nacional de Salud, las cuales pueden solicitarse en cnm-laboratorios.isciii.es. Jefe del Laboratorio: Jesús Oteo Iglesias (Punto focal Nacional de Resistencia antibiótica).

Dispone de dos programas de Vigilancia oficiales y gratuitos que engloban los ensayos ofertados ya sea como aislamientos individuales o mediante estudio de brotes. El Laboratorio utiliza asimismo técnicas de PCR en tiempo real para la detección de genes de resistencia, estas técnicas se han adaptado a un formato multiplex que permite detectar varios genes en la misma reacción. En los últimos años se han incluido metodologías basadas en la secuenciación de genomas completos para el análisis de bacterias multiresistentes (WGS).

Programa de vigilancia de Haemophilus influenzae. Responsables: María Pérez Vázquez (Punto focal Nacional de Haemophilus influenzae) y Belén Aracil. Laboratorio encargado de la identificación, estudio de sensibilidad y análisis genotípico de aislados de Haemophilus influenzae, centrándose esencialmente en la patología invasiva debida este patógeno. 

Programa de vigilancia de Resistencia a Antibióticos. Responsables: María Pérez Vázquez  y Belén Aracil (Punto focal Nacional de Resistencia antibiótica). Laboratorio encargado de la identificación, el estudio de sensibilidad antibiótica, y el diagnóstico fenotípico y genotípico de los diferentes mecanismos de resistencia a antibióticos fundamentalmente en enterobacterias y gram-negativos no fermentadores y Enterococcus spp.

Estudio de brotes. Responsables: Belén Aracil y María Pérez Vázquez. El programa incluye la caracterización de brotes nosocomiales y clones emergentes de alto riesgo mediante diferentes técnicas moleculares (tabla resumen). Éstas, nos permiten realizar estudios filogenéticos con el fin de obtener una información detallada acerca la relación entre los diferentes aislados y su trazabilidad. El objetivo final es generar datos que se transfieren a los hospitales como ayuda para la prevención o control de la propagación del brote.

Acreditación y Calidad. Responsable: Belén Aracil. El laboratorio Referencia e Investigación en Resistencia a Antibióticos ha sido de los primeros en el ISCIII en la utilización de técnicas acreditadas por la Entidad Nacional de Acreditaciones (ENAC). Este laboratorio consiguió la primera acreditación homologada de técnicas diagnósticas en 2012, programa que ha sido ampliado, de manera que en la actualidad más de la mitad de las técnicas ofrecidas al Sistema Nacional de Salud están debidamente acreditadas por ENAC.

Técnicos responsables de las técnicas realizadas en el Laboratorio: Noelia Lara Fuella y Verónica Bautista Sánchez.

En la siguiente imagen se resumen las técnicas ofrecidas al Sistema Nacional de Salud.

PROGRAMAS NOMBRE CARTERA SERVICIO PATÓGENO DETERMINACIÓN, DETECCIÓN, ANÁLISIS MÉTODOS

Programa de vigilancia de Haemophilus

Programa de vigilancia de resistencia a antibióticos.

Identificación bacteriana

Haemophilus sp.

Enterobacterias, gram-negativos no fermentadores, Enterococcus spp

Identificación bacteriana

Bioquímicos

MALDI TOF

Secuenciación de RNAr

Identificación capsular

Haemophilus influenzae

 

Identificación capsular fenotípica y genotípica

Aglutinación serológica en latex

PCR ind/multiplex

Determinación de Sensibilidad

Haemophilus sp.

Enterobacterias, gram-negativos no fermentadores, Enterococcus

 

Determinación de Sensibilidad

Microdilución                

Tiras epsilon               

Kirby Bauer

Métodos fenotípicos de detección de mecanismos de resistencia

Enterobacterias, gram-negativos no fermentadores,

 

Métodos fenotípicos de detección de mecanismos de resistencia

Discos y tabletas combinados con inhibidores                

Tiras combinadas     

Test de Hodge modificado

CabaNP                               

Inmunocromatografía CBP

Métodos genotípicos de detección de mecanismos de resistencia

Haemophilus sp.

Enterobacterias, gram-negativos no fermentadores, Enterococcus

 

ADN, PCR y secuenciación

PCR ind/multiplex

Análisis comparativo de las secuencias

Tipificación molecular/análisis filogenéticos

Haemophilus sp.

Enterobacterias, gram-negativos no fermentadores, Enterococcus

 

Corte enzimas de restricción, electroforesis

ADN, PCR y secuenciación

Preparación de librerías y secuenciación y análisis de genomas completos

 

PFGE

 

MLST

 

WGS