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Investigation
Viral Biology
Research Lines
Content with Investigacion .
The Immunobiology group has been working for years on the following lines of research:
1) The mechanisms of haematopoietic cell generation throughout ontogeny and the influence that the first haematopoietic cells exert on the innate and adaptive immune system present in the adults. We have identified and characterised a new population of B lymphocytes called B1-Rel (B220lo), which produce high levels of natural IgG/IgA antibodies. We sought to understand their role in the immune response in animal models of infection, analysing their impact on immune cell populations and on the production of soluble mediators (cytokines and immunoglobulins). In this regard, we have evaluated the generation of embryonic megakaryocytes (and their differentiation niches), their functionality and that of platelets, and their influence on haematopoietic development. For lymphoid populations, we have carried out extensive characterisation by flow cytometry and single cell RNA sequencing (scRNAseq) methodology. To carry out these cellomic studies, we have designed complex panels for use in multiparametric phenotypic analysis, and single cell cytometry and RNAseq omics technologies on purified cell populations.
In parallel, we are interested in understanding local immune responses in respiratory infections at times of particular susceptibility due to the fragility of the immune system (childhood and old age), both in mouse animal models, which allow their manipulation, and in humans.
2) Mouse models studied during neonatal life, in which we evaluated the effect of antibiotic (AB) treatment and addressed the role of TLR receptors in innate, pseudo-innate and adaptive immune cell populations. In these models, we observed that AB administration was able to modulate B-lymphoid populations, as well as their ability to secrete proinflammatory cytokines in culture and their differentiation into plasma cells, with differentiated immunoglobulin repertoires. Furthermore. These effects were mediated through the Toll-like receptor-2 (TLR2).
3) Mouse models with accelerated senescence (SAMP8) and senescent animals (over 20 months of age) to map lymphoid populations and soluble mediators of the immune response (immunoglobulins and cytokines). In these models, the B lymphoid populations (B1Rel and marginal zone B lymphocytes) are observed to be altered, accompanied by an increase in IgG1 with great restriction of their VDJ repertoires.
4) Role of the B1Rel population in animal models of local or systemic infection. We analysed the response to Streptoccoccus pneumoniae (SPN) locally in the lung and systemically in the spleen, as well as the role of TLR4 in these responses.
5) In humans, we are studying immune responses in children with respiratory syncytial virus (RSV) viral primo-infection. In this case we studied the immune response that occurs locally in the nasal mucosa (by analysis of nasal washings, NW) in a cohort of infected children versus healthy controls, stratified by age. We found that lymphomyeloid cells accumulate in these nasal washings in patients with diverse lymphocyte populations, as well as cytokines and immunoglobulins.
6) Analysis and characterisation of extracellular vesicles produced during respiratory infection both in lung supernatants from models of SPN infection and in LN in the case of children with RSV infection.
7) In parallel, we carry out studies of the genetic rearrangements of immunoglobulins and their use in the generation of chimeric receptors for possible use in immunotherapy.
Research projects
Content with Investigacion .
-Project “Induction, differentiation and modulation of resident B lymphocytes in the lung in response to pneumococcus (NEUBLUNG)”. Ministry of Science and Innovation, PID2022-141754OB-I00 Call 2022 "Knowledge Generation Projects". 09/01/2023-08/31/2026. Financed by MICIU/AEI /10.13039/501100011033 and by ERDF, EU. PI: Belén by Andrés Muguruza. CoPI: María Luisa Gaspar Alonso-Vega.
-Project." Immune response of the nasal mucosa in childhood bronchiolitis” Instituto de Salud Carlos III-AESI. AESI-PI22CIII/00030 PI: Belén by Andrés Muguruza. CoPI Maria Luisa Gaspar Alonso-Vega. 01/01/2023-12/31/2025..
-Project. BenBedPhar. CA20121, European Union. Antonio Cuadrado. (CNM-ISCIII).10/19/2021-10/18/2025.
-Spanish Association Against Cancer Project “Novel comprehensive immunotherapy to specifically target the malignant clone in Sézary syndrome, an ultra-rare cancer of mature T lymphocytes”, number PROYE20084REGU. PI: José Ramón Regueiro, PI group Maria Luisa Gaspar. 01/01/2021-12/31/2023.
Project “The pulmonary immune system in homeostasis and infection: characterization and function of immature and pseudoinnate lymphoid populations.” MINECO-RETOS RTI2018-099114-B-100. PI: Maria Luisa Gaspar, CoPI: Belén de Andrés 01/01/2019-12/31/2022. Financed by MICIU/AEI /10.13039/501100011033/ and by FEDER A way of making Europe.
-Project “New B lymphoid populations: B1-rel pseudoinnate cells, homeostatic maintenance and their response under infection conditions.” MINECO-RETOS SAF2015-70880-R. PI: Maria Luisa Gaspar. 01/01/2016-12/31/2019.
-Project “Role of CD19+CD45R lymphocytes- in perinatal immune responses. Implications related to respiratory diseases in neonates. AESI PI14CIII/00049; PI Belén de Andrés. 2015-2018.
-Project “Study of the pseudo-innate population of CD19+CD45R- B lymphocytes in TLR-dependent infection models”. AESI PI11/01733FIS. PI Belén de Andrés. 2012-2015.
-Project." Cellular interactions in the establishment of B lymphoid differentiation niches: role of megakaryocytes and their implications in pathology. MINECO; SAF2012-33916. Maria Luisa Gaspar. 01/01/2013-12/31/2015.
-ISCIII Platforms Project to support R&D&I in Biomedicine and Health Sciences. PT23CIII/00006. 2023. Participating researcher: Isabel Cortegano.
-Research contracts between the Carlos III Health Institute and Inmunotek S.L. for the development of the Bactek-mv130 and Uromune-MV140 study in protection against S. pneumoniae infections. Immunotek. IP: Belen de Andrés 2019-2021.
-Research contract between the Carlos III Health Institute and Inmunotek S.L. “MV130 as a vaccine model based on trained immunity against respiratory infections due to pneumococcus and respiratory syncytial virus”, CAM Call. Industrial Doctorates. IND2023/BMD-27071. PI: Belén by Andrés Muguruza. 12/01/2023-11/30/2026.
Publications
Definition of the viral targets of protective HIV-1-specific T cell responses
Mothe B, Llano A, Ibarrondo J, Daniels M, Miranda C, Zamarreno J, Bach V, Zuniga R, Perez-Alvarez S, Berger CT, Puertas MC, Martinez-Picado J, Rolland M, Farfan M, Szinger JJ, Hildebrand WH, Yang OO, Sanchez-Merino V, Brumme CJ, Brumme ZL, Heckerman D, Allen TM, Mullins JI, Gomez G, Goulder PJ, Walker BD, Gatell JM, Clotet B, Korber BT, Sanchez J, Brander C; J Transl Med. 2011 Dec 7;9:208
PUBMED DOIShortcomings of the commercial MALDI-TOF MS database and use of MLSA as an arbiter in the identification of Nocardia species
Carrasco G, de Dios Caballero J, Garrido N, Valdezate S, Cantón R, Sáez-Nieto JA. Shortcomings of the commercial MALDI-TOF MS database and use of MLSA as an arbiter in the identification of Nocardia species. Front Microbiol. 2016 21;7:542.
PUBMED DOIContent with Investigacion .
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María Luisa Gaspar Alonso-Vega
Research Professor
ORCID code: 0000-0001-9858-3862
Dr. María Luis Gaspar Alons-Vega graduated in 1980 and obtained her PhD in 1985 in Medicine and Surgery from the Autonomous University of Madrid. She completed the specialty of Immunology (1981-1985), and her doctoral thesis under the direction of Dr. Carmen Gutierrez, in the Immunology laboratory of the Puerta de Hierro Clinic directed by Dr. Miguel Kreisler. She completed a predoctoral stay in the Cytogenetics Laboratory of the National Institute of Autoimmune, Diabetes, Digestive and Kidney Diseases (NIDDK, NIH), under the supervision of Dr. JH Tjio and Dr. E. Raveché. She joined the Immunology Service of the National Center for Health Microbiology, Virology and Immunology (CNMVIS, AISNA and later ISCIII) as a Physician-Specialist in 1986, in the Immunology Laboratory directed by Dr. Alfredo Toraño. She completed a postdoctoral stay (1989-1991) at the Immunogenetics Unit of the Pasteur Institute (Paris) directed by Dr. T. Meo. From 1991 to 2006 she was Head of the Immunology Section successively at the CNMVIS, at the National Center for Fundamental Biology (CNBF-ISCIII) and at the National Center for Microbiology (CNM-ISCIII). From 2006 to 2016 she has been a Senior Researcher and Senior Scientist of OPIs, in the Immunobiology laboratory of the CNM-ISCIII. From 2016 to 2018 she was a Scientific Researcher at OPIs and since 2018, she is a Research Professor at OPIs at the CNM.
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Belén de Andrés Muguruza
Research Scientist
ORCID code: 0000-0002-7391-2823
Graduated in Biology in 1987 and PhD in 1992 from the Autonomous University of Madrid. He completed his doctoral thesis in the laboratory of Dr. Carlos Lahoz in the Immunology department of the Jiménez Díaz Foundation with a pre-doctoral stay at the Institute Curie in Paris, in the laboratory of Dr. Wolf H. Fridman. Subsequently, he completed a two-year postdoctoral stay in the Department of Pathology of the College of Medicine at the University of Iowa, USA, in the laboratory of Dr. Richard G. Lynch. After a year as an Adjunct in the Immunology department of the Jiménez Diaz Foundation, she worked for 2 years with a reinstatement contract from the Ministry of Science in the Immunobiology department of the CNM/ISCIII in the laboratory of Dr. Mª Luisa Gaspar and later with a Ramón y Cajal contract. In 2006 she obtained a position as Staff Senior Scientist.
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Isabel Cortegano Jimeno
Research Scientist
ORCID code: 0000-0002-6504-6347
Graduated in Biology in 1995 (Specialty in Biochemistry and Molecular Biology) and PhD in 1999 from the Autonomous University of Madrid. He completed his doctoral thesis at the Jiménez Díaz Foundation in the Immunology laboratory directed by Dr. Carlos Lahoz. Later he obtained a postdoctoral fellowship in the Immunobiology laboratory of Dr. Mª Luisa Gaspar at the National Center of Microbiology (CNM) of the Carlos IIII Health Institute (ISCIII) (2002-2006). He then enjoyed an I3P contract from the CSIC in the laboratory of Professor Miguel Ángel Rodríguez-Marcos (2007-2009). She has been a researcher associated with research projects in the ISCIII Immunobiology laboratory during the years 2010-2018. Since 2018 she has been an associate professor in the Department of Cell Biology of the UCM Faculty of Medicine. He coordinates the scientific dissemination group of the Spanish Society of Immunology (GESEI), is part of the editorial committee of the SEI magazine and is a member of the board of the CAM Immunology Society. She is a Senior Scientist of the ISCIII at the National Center for Microbiology since 2020.
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Carolina Ruiz Sánchez
Specialized Technician
ORCID code: 0000-0002-2177-8132
Graduated in Chemical Sciences (biochemistry specialty) in 1998 and PhD in 2022 from the Complutense University of Madrid. In 2008 he joined the OPIS Assistant in the Immunobiology laboratory of the National Center for Microbiology of the ISCIII, specializing in flow cytometry the first year and subsequently becoming part of the laboratory's technical team. In 2012 he was promoted to Intermediate Level Technician and in 2018 to Higher Specialized Technician of the OPIS, currently occupying this position in the same laboratory.
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Mercedes Rodríguez García
Specialized Higher Technician
Graduated in Biology from the Complutense University of Madrid in 2003, she began her doctoral studies in the Bone Metabolism laboratory of the La Paz University Hospital.
In 2007 he joined as a Research Assistant at the Carlos III Health Institute, at the CNM, in the Transplant Immunology laboratory. After 5 years, he began working in the Immunobilology laboratory where he was promoted in 2018 to Specialized Technician, in 2024 to Senior Specialized Technician and where he currently continues to develop his professional career. -
Alejandro Arrabal Sierra
Predoctoral Contract (Industrial Doctorate from CAM / Inmunotek).
ORCID code: 0000-0002-9354-9224
Graduated in Biotechnology in 2021 from the Polytechnic University of Madrid, carrying out his final degree project in the Immunobiology laboratory of the National Microbiology Center of the ISCIII. In 2021, he completed a Master's Degree in Research in Immunology at the Complutense University of Madrid and completed his master's thesis in the same CNM laboratory. Subsequently, he worked for a year as a Research Assistant in the laboratory of Dr. Elena Fernández Ruiz at the Hospital Universitario de la Princesa. Since the end of 2023, he has been a predoctoral fellow in the CNM Immunobiology laboratory with an Industrial Doctorate scholarship from the Community of Madrid in collaboration with the company Inmunotek.
List of staff
Additional Information
The research activity of the Viral Biology group since its beginnings in the 1980s has focused on respiratory viruses, especially on the study of the mechanisms of virus entry into the cell, evolutionary aspects, antigenic properties and vaccine development.
Currently, the group's objectives are focused on the characterisation of the immune response and the development of vaccines against human pneumoviruses: human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV).
Both viruses are considered to be important respiratory pathogens of high clinical relevance, especially in the paediatric population.
Safe and effective vaccines against these viruses are currently not available. Soluble protein subunits based on the fusion protein (F-protein) of hRSV and hMPV are being developed in the laboratory by protein engineering for use as vaccines against human pneumoviruses.
On the other hand, and thanks to the characterisation of the type of humoral response induced by the F proteins of these viruses, the laboratory is also involved in the isolation of monoclonal antibodies and nanoantibodies for use as treatments against these viruses.
The research activity of the Viral Biology group since its beginnings in the 1980s has focused on respiratory viruses, especially on the study of the mechanisms of virus entry into the cell, evolutionary aspects, antigenic properties and vaccine development.
Currently, the group's objectives are focused on the characterisation of the immune response and the development of vaccines against human pneumoviruses: human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV).
Both viruses are considered to be important respiratory pathogens of high clinical relevance, especially in the paediatric population.
Safe and effective vaccines against these viruses are currently not available. Soluble protein subunits based on the fusion protein (F-protein) of hRSV and hMPV are being developed in the laboratory by protein engineering for use as vaccines against human pneumoviruses.
On the other hand, and thanks to the characterisation of the type of humoral response induced by the F proteins of these viruses, the laboratory is also involved in the isolation of monoclonal antibodies and nanoantibodies for use as treatments against these viruses.