Maria Montoya’s (MM) has worked in pig immunology for the last thirteen years, studying immune responses to viruses affecting pigs, such influenza virus, and generating novel vaccine strategies. She has a long track record in viral immunology in different species and systems with international collaborations worldwide. MM has worked with a variety of pathogens under SAPO4 conditions for 15 years. She has been PI on several successful grants and published more than 60 papers in peer reviewed journals (Nature, Journal of Immunology, Blood, Veterinary Research, Plos Pathogens, Scientific Reports, Journal of Virology, Plos One...). MM support the efforts to improve the role of women in science as well as participate in outreaching activities for the general public.
Aims and objectives of the group
In the last decades, the mouse model tremendously contributed to the progress of research in immunology. However, it is worth noticing that research in large/unconventional animals has given pivotal information to immunology in general. The need for translational immunological research, the development of new animal models more adapted to the scientific question, and the acquisition of new knowledge in comparative immunology is increasing in importance every year.
The main aim of the group is to provide new insights into immunological host-pathogen interactions by studying the immune system of the pigs in the context of natural relevant viral infections. All previous experience has been used to study inflammatory mechanisms of SARS-CoV-2. Pigs will be used as model for cellular therapies or viral infections.
Viral infections continue to cause considerable morbidity and mortality around the world. Besides its importance as a zoonotic agent, Swine Influenza Virus (SwIV) is a relevant porcine respiratory disease. African swine fever virus (ASFV) causes severe disease in domestic pigs resulting in up to 100% mortality and there is no vaccine. SARS-CoV-2 is a new type of coronavirus causing the actual pandemic worldwide. New approaches are required to fight viral diseases, which can only be informed by a deeper knowledge of immune responses during host-pathogen interactions. The work in the group is directed into a better understanding of the immune responses required for protection against viral diseases.
Our team have applied reverse vaccinology to identify SLA-I and SLA-II T-cell epitopes from SwIV H1N1. Recognition of overlapping peptides from H1N1 revealed a novel SLA class II restricted epitope in NP. This conserved novel epitope could be the base for further vaccine approaches against H1N1 SwIV in pigs (Fig 1).
Extracellular vesicles (EVs) have proven to be a promising new vaccination platform in situations in which conventional approaches have not been completely successful. Serum EVs from infected pigs using two different ASFV viruses were characterized. Proteomic analysis revealed few specific proteins from ASFV in the EVs, but 942 swine proteins were detected in all EV preparations. Most of these were related to coagulation cascades. The results obtained contribute to a better understanding of ASFV pathogenesis and immune/protective responses in the host.
The pathophysiology of SARS-CoV-2 has not been well characterized. Particularly, the reason why some people develop an exacerbated inflammation leading to disease severity remains obscure. We are working to build up a cellular platform designed to establish viral determinants that may modulate inflammation and/or cell death (Fig 2). These findings will be used to develop novel approaches to counteract inflammation as a possible treatment.
Natalia Redondo, Sara Zaldívar-López, Juan J Garrido, Maria Montoya . SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns
Montaner‐tarbes, S., Fraile, L., Montoya, M., Del Portillo, H. . Exosome‐based vaccines: Pros and cons in the world of animal health. Viruses. 13:-.
Grigas, J., Montoya, M., Simkute, E., Buitkus, M., Zagrabskaite, R., Pautienius, A., Razukevicius, D., Jonaitis, L.V., Kiudelis, G., Skieceviciene, J., Vaiciuniene, R., Stankuviene, A., Bumblyte, I.A., Kupcinskas, J., Stankevicius, A. . Molecular characterization and seroprevalence of hepatitis e virus in inflammatory bowel disease patients and solid organ transplant recipients. Viruses. 13:-.
Pujol, M., Guzman, E., Montaner-Tarbes, S., Montoya, M. . Heterogeneous populations from in vitro cultures of antigen presenting cells in pigs. Veterinary Immunology and Immunopathology. 234:-.
Sánchez-Cordón, P.J., Jabbar, T., Chapman, D., Dixon, L.K., Montoya, M. . Absence of long-term protection in domestic pigs immunized with attenuated african swine fever virus isolate OURT88/3 or Benin∆MGF correlates with increased levels of regulatory T cells and interleukin-10. Journal of Virology. 94:-.
Baratelli, M., Morgan, S., Hemmink, J.D., Reid, E., Carr, B.V., Lefevre, E., Montaner-Tarbes, S., Charleston, B., Fraile, L., Tchilian, E., Montoya, M. . Identification of a Newly Conserved SLA-II Epitope in a Structural Protein of Swine Influenza Virus. Frontiers in Immunology. 11:-.
Goatley, L.C., Reis, A.L., Portugal, R., Goldswain, H., Shimmon, G.L., Hargreaves, Z., Ho, C.-S., Montoya, M., Sánchez-Cordón, P.J., Taylor, G., Dixon, L.K., Netherton, C.L. . A pool of eight virally vectored African swine fever antigens protect pigs against fatal disease. Vaccines. 8:-.
Vidaña, B., Martínez-Orellana, P., Martorell, J.M., Baratelli, M., Martínez, J., Migura-Garcia, L., Córdoba, L., Pérez, M., Casas, I., Pozo, F., Fraile, L., Majó, N., Montoya, M. . Differential viral-host immune interactions associated with oseltamivir-resistant H275Y and wild-type H1N1 A(pdm09) influenza virus pathogenicity. Viruses. 12:-.
Guzman, E., Pujol, M., Ribeca, P., Montoya, M. . Bovine derived in vitro cultures generate heterogeneous populations of antigen presenting cells. Frontiers in Immunology. 10:-.
Selected competitive grants from 2016:
- COST Action. “Understanding and combating African Swine Fever in Europe” (ASF-STOP); OC-2015-1-19550COST Action. 2014-2019. 135,573.50 €.
- MINECO. Title: "New approaches in vaccine development against livestock viral diseases using engineered virus-like particles”. IP WG1: M Montoya AGL2013-48923-C2-2-R. 2014. 150.000€
- BBSRC. Title: “Epitope characterization for rational vaccine development”. BBS/E/I/00002014. IP: M Montoya. 2014-2017. £47.163
- I+COOP+2019. Title: “Cooperación en inmunología avanzada: capacitación de técnicas y diseño de curso de grado y postgrado”. COOPB20438 IP: M Montoya. 2019-2021. 23.550€
- VetBioNet: Title: “Use of extracellular vesicles as immunogens for African Swine Fever Virus” IP: M Montoya. 2020. 63.550€
- PTI Salud Global CSIC. Inflammation viral determinants in the cytokine storm within COVID-19 (COVID-19-117) IP: M Montoya. 2020. 117.000€
- Junta de Andalucía: Inflammation viral determinants in the cytokine storm within COVID-19 (CV20-20089). IP: JJ Garrido. 2020. 80.000€
- CDTI-CSIC. Desarrollo de una vacuna sintética de ADN frente a la infección por el virus SARS-CoV2. IP: Vicente Larraga
- PTI Salud Global CSIC. Inflammation viral determinants in the cytokine storm within COVID-19 (COVID-19-117) IP: M Montoya. 2020. 439.150€
MARIA MONTOYA GONZALEZ
Master in Immunology 1991-1992. University of Birmingham, UK.
PhD: 1997, Universidad Autonoma de Madrid, Spain
Post-doctoral and Fellow Scientist: 1998-2005. The Edward Jenner Institute. UK
Group leader: 2005-2014. Centre de Recerca en Sanitat Animal (CReSA). Barcelona, Spain
Group leader: 2014-2017. The Pirbright Institute. UK
EU patent “Exosomes and their use as vaccine”. P3249PC00. 2016. H. A. del Portillo, F. E. Borras, L.J. Fraile, S.R. Montaner, M. Montoya.
"The CIBMS DNA vaccine against Covid 19" by P.J. Alcolea, J. Larraga, A. Alonso, F. Loayza, M. Oliva, M. Montoya, V. Larraga. Submitted to the Patent Office by Hoffmann SL. (in progess).
Both patents have been subcontracted and in development by other companies at the moment.
Innovex Therapeutics SL. (https://innovexther.com/ )
Investigador Distinguido: 2018. Centro de investigaciones Biológicas (CIB), Madrid, Spain