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Immune precision medicine as a new opportunity to control canine trypanosomatid diseases - DogIPM PTDC/CVT-CVT/0228/2020

  • Background: The project DogIPM’s main objective is to stimulate dendritic cells (DC) that present essential antigens for the activation of T lymphocytes, which in turn orchestrate the host's immune response to guide the immune system in the fight against trypanosomatids, preventing infection (prophylactic vaccines) or inducing the most adequate immune response to cure (therapeutic vaccines). 
  • Aim: DogIPM aims to stimulate immune effector cells to tutor the immune system in combating trypanosomatids, preventing infection (prophylactic vaccines) or inducing the most appropriate immune response to cure (therapeutic vaccines).
  • Innovation: Envisioning the potential use of autologous stimulated DC as a prophylactic and therapeutic tool against cardiac Chagas disease and Leishmaniasis, DogIPM represents a first step in precision immune medicine applied to canine diseases caused by trypanosomatids. This immune approach represents a new and promising strategy applicable to the control of trypanosomoses.
  • Expectations: DogIPM is expected to make a valid contribution to controlling Leishmania and Trypanosoma infection, reducing the amount, frequency of administration and toxicity of commonly used drugs, decreasing the duration of therapy, improving treatment adherence and achieve clinical and parasitic cure. DogIPM is also expected to participate in student education and communication of science and technology, improving global awareness of the strategic importance of science in the daily lives of citizens.

PARTNERS

GHTM–Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), Lisboa, Portugal

Faculdade de Medicina Veterinária (FMV), CIISA Centro de Investigação Interdisciplinar em Sanidade Animal, Universidade de Lisboa, Lisboa, Portugal,

Health Sciences Centre/Federal University of Rio Grande do Norte 
(UFRN, Natal, Brasil)



PROJECT OUTCOME
• 1º seminário Outubro 2022

PUBLICATIONS

Tatiana Dias-Guerreiro, Joana Palma-Marques, Patrícia Mourata-Gonçalves, Graça Alexandre-Pires, Ana Valério-Bolas, Áurea Gabriel, Telmo Nunes, Wilson Antunes, Isabel Pereira da Fonseca, Marcelo Sousa-Silva, Gabriela Santos-Gomes (2021). African Trypanosomiasis: Extracellular vesicles shed by Trypanosoma brucei brucei manipulate host mononuclear cells. Biomedicines, 9(8): 1056.

ACADEMIC DEGREES

- Mafalda Carvalho Planas Meunier  (2021/2022) - Leishmaniose canina: Explorar a modulação da atividade de linfócitos T por células dendríticas autólogas. Master’s thesis, Masters in Biomedical Sciences – Institute of Hygiene and Tropical Medicine (IHMT), Universidade Nova de Lisboa (UNL), Lisbon, Portugal. Supervision: Prof. Gabriela Santos-Gomes & Dr. Armanda Rodrigues - IHMT, Medical Parasitology Teaching and Research Unit (ongoing).

- Ana Sofia Valério Bolas (2016-2022) - Bridging the gap between innate and adaptive immunity in dog leishmaniosis. FCT doctoral fellowship SFRH/BD/118067/2016 e COVID-19 mitigation grant. PhD Program in Biomedical Sciences, specialty in Parasitology. Institute of Hygiene and Tropical Medicine (IHMT), Universidade Nova de Lisboa (UNL), Lisbon, Portugal. Supervision: Prof. Gabriela Santos-Gomes - IHMT, Medical Parasitology Teaching and Research Unit and Prof. Isabel Pereira da Fonseca (Co-supervisor) - Faculdade de Medicina Veterinária, CIISA–Centro de Investigação Interdisciplinar em Sanidade Animal, Universidade de Lisboa (ongoing).

- Joana Palma Machado Marques (2021-2025) - Dogs in travel - Take advantage of dendritic cells to shape protective immune response against Chagas disease. PhD Program in Biomedical Sciences at the Institute of Hygiene and Tropical Medicine (specialization in cellular and molecular biology and parasitology) - Universidade Nova de Lisboa (Lisbon, Portugal). Supervision: Prof. Gabriela Santos-Gomes (Supervisor) - IHMT, Medical Parasitology Teaching and Research Unit. Prof. Graça Maria Alexandre-Pires (Co-Supervisor) - Faculdade de Medicina Veterinária - Centro de Investigação Interdisciplinar em Sanidade Animal, Departamento de Morfologia e Função e Departamento de Sanidade Animal Unidade de Lisboa, Advanced Specialization Programs (ongoing).


PRESENTATIONS

Valério-Bolas, S. Mesquita-Gabriel, M. Meunier, J. Marques, L. Lobo, A. Rodrigues, A. Armada, R. Ferreira, I. Cardoso, G. Alexandre-Pires, I. Pereira da Fonseca, G. Santos-Gomes. Leishmaniose canina: Iniciação da resposta imunitária por células dendríticas derivadas de monócitos caninos. XI Jornadas Científicas HMT-NOVA, 10 de dezembro de 2020. Abstract book page 4.

A. Valério-Bolas, S. Mesquita-Gabriel, M. Meunier, J. Marques, L. Lobo, A. Rodrigues, A. Armada, R. Ferreira, I. Cardoso, G. Alexandre-Pires, I. Pereira da Fonseca, G. Santos-Gomes. Modulation of dendritic cells derived from canine monocytes by parasites of the genus Leishmania. Encontro Ciência 2021. 28 a 30 junho. Centro de Congressos de Lisboa, Junqueira - Portugal

TRAINING

Prof. Doutora Mariana Machado Hecht, Faculty of Medicine, University of Brasilia.

Raissa Couto Santana, Graduate Program in Veterinary Science (PPGCV) Department of Veterinary Microbiology and Immunology (DMIV) Veterinary Institute (IV), Federal Rural University of Rio de Janeiro - UFRRJ. Sandwich PhD scholarship from the Coordination for the Improvement of Higher Education Personnel (CAPES) entitled “Analysis of the Effect of Sesquiterpene on the Immunobiology of Canine Leishmaniasis”. September 2021 - March 2022.

NEWS

Parasitic diseases - approach to personalized healthcare

The partnership between Portuguese [Global Health and Tropical Medicine (GHMT), Institute of Hygiene and Tropical Medicine (HMT-NOVA) and Faculty of Veterinary Medicine (FMV/ULisboa)] and Brazilian institutions [Health Sciences Center of the Federal University of Rio Grande do Norte (UFRN)] resulted in the project DogIPM, financed by the Foundation for Science and Technology, I.P. which aims to use dendritic cells (DCs) to modulate T lymphocyte activity in canine trypanosomoses.

Annually there are an estimated 700 000 - 1 million new cases of infection with Leishmania in humans, and 20 000 new cases per year of infection with Trypanosoma cruzi.

L. infantum is the etiologic agent of zoonotic visceral leishmaniasis and canine leishmaniasis that occur throughout the Mediterranean basin, the Middle East, and in some parts of Asia and Latin America. Canine leishmaniasis appears to be spreading to other latitudes due to several factors associated with climate change and globalization.

Trypanosoma cruzi parasite causes Chagas disease in humans, wild and domestic animals, constituting an important public health problem in Central and South America. Due to globalization, this neglected tropical disease has been spreading to other geographic areas, such as North America, Japan, Oceania, and Europe, becoming an emerging disease of global concern. So far, there is no vaccine available to prevent ChD or targeted animal therapy.

The project DogIPM represents a first step in precision immune medicine applied to canine diseases caused by trypanosomatids. These tools will make it possible to control the infection, reduce the amount, frequency of administration and toxicity of non-specific therapy currently used, improve treatment adherence, and achieve clinical and parasitic cure.

The researchers of the DogIPM project thus hope to make a valid contribution to controlling Leishmania and Trypanosoma infection, with the development of vaccines to prevent the infection or inducing the most adequate immune response to cure. Controlling neglected parasitic diseases will contribute to improving the health care available to animals and people and will have a positive impact on the evolution of society.


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Funding

FCT – Immune precision medicine as a new opportunity to control canine trypanosomatid diseases – DogIPM PTDC/CVT-CVT/0228/2020

Contacts

PI
Prof. Gabriela Santos-Gomes
SantosGomes@ihmt.unl.pt

co-PI 
Prof. Isabel Pereira da Fonseca
ifonseca@fmv.ulisboa.pt

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