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Rachel BRAS-GONCALVES

Directrice de recherche DR2
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Curriculum vitae - Biographical sketch NAME: BRAS-GONCALVES, Rachel POSITION TITLE: Senior researcher/Director of research- Co-leader of the research axis “New preventive, diagnostic and therapeutic approaches” - Head of research group “Immunology, Vaccine & Diagnosis of leishmaniases”. Institution / Research unit: IRD - UMR177 INTERTRYP EDUCATION/TRAINING - 1994 MSC University of Nancy, France Field of study: Biochemistry - 1998 PhD University of Paris 7, France Field of study: Health Biology - 2018 HDR(Tenure) University of Montpellier, France Field of study: Health Biology A. Personal Statement I am an immunologist with more than twenty years of experience in the areas of Host-Leishmania interactions, immune tolerance and relationships between peptide/HLA interaction and immunogenicity. My current research interests focuse on the host immune response against Leishmania infection, the induction of immune response to prevent Leishmaniasis from the design of dynamic and original vaccines, and the proposal of new diagnostic approaches. I have a long working experience in partner's laboratories from endemic regions for leishmaniases for the strengthening of research teams from LMICs within the framework of scientific partnerships. I was posted to: - Varanasi (India, three months, 2004) to support the Indian laboratory “Infectious Diseases Research Laboratory” (Pr S. Sundar, Banaras Hindu University (BHU), Varanasi, India), through transfer of scientific and technical skills and supervision of three doctoral students, among them Krishna Das Manandhar, and a post-doctoral fellow. - New Delhi (India, two months in 2009 and in 2011) in the Indian National Institute of Pathology NIP-ICMR partner of the EU FP7-RAPSODI project (Pr. P. Salotra), to support the training and supervision of three PhD students and the completion of the protocols related to the project work packages. - Kathmandu (Nepal, fifteen-days 2009) to visit the Central Department of Biotechnology of Tribhuvan University, directed by Pr. Krishna Das Manandhar, for the evaluation of research capacities of the center for the development of collaborative projects, and support Krishna for an IRD-BEST postdoctoral fellowship request. - Tunis (Tunisia, two months in 2013, in 2014 and in 2015) in order to support Dr. A. Garnaoui for her "Young Associated Team at IRD" (JEAI - VACLEISH, IRD's Means of research support) with transfer of scientific and technical skills, supervision of students (1 Master and 2 PhD students) and provide a seminar-workshop on “Peptide vaccines”. - Lima (Peru, two months, 2017) to a scientific support for the Patho-Antigens laboratory (Pr. Jorge Arevalo) of the Universidad Peruana Cayetano Heredia (UPCH) for the drafting of funding request files, in particular: JEAI-IRD, acquisition of a flow cytometer, and first drafts of a project proposal to respond to the EU call H2020-SC1-BHC-15-2018. B. Positions and Honors Education and Positions 2017- present Senior researcher/Director of research IRD. UMR177 INTERTRYP - Head of research group “Immunology, Vaccine & Diagnosis of leishmaniases” 2008-2017 Researcher IRD, Montpellier. UMR177 INTERTRYP 2011-present Co-leader of the research axis “New preventive, diagnostic and therapeutic approaches” of UMR177. Participation in the evaluations of the AERES (Jan-2010 & Dec-2013) and HCERES (Jan-2020) commissions, as co-leader for one of the laboratory's thematic research axes (reports: current situation and perspectives, and oral presentations) 2002-present Supervision of PhD students, Master I (MSC-I) and Master II (MSC-II), Bachelor of Science (BSC), member of PhD defense juries, and jury member of CBS2 doctoral school scholarships (Univ Montpellier) 2002-2007 Researcher IRD, Montpellier. UR008 Molecular factors involved in the pathophysiology, prevention and epidemiology of Chagas disease and leishmaniasis. Permanent position. 1998-2002 Post-doctoral researcher - Institut Cochin, Department of Immunology (Inserm U567, CNRS UMR 8104, Université Paris V René Descartes), Paris. Director of the J G. Guillet department. Subject: Study of the physiopathology and post-vaccination follow-up of infectious (HIV, HCV) and tumor (melanoma) diseases. 1994-1998 PhD student - Hematology-immunology research service - French Alternative Energies and Atomic Energy Commission (CEA) - Institute of Hematology, Saint Louis Hospital, Paris. CEA funding. Thesis director M. Kirszenbaum. Subject: Expression and characterization of the HLA-G antigen. Study of immunological functions. From the cloning of the HLA-G antigen to its immunotolerant functions and its implications in transplantation and tumor pathologies. Professional Memberships and Activities 2021-present Expert for the French ministry of higher education research and innovation – Fiscal written and approval for Research Tax Credit and Young Innovative Company 2021-present Member of the UMR177 Unit Council 2016-present Member of the Vaccine research consortium CoReVac and ITMO I3M 2016-present Member of the French-speaking Network on Neglected Tropical Diseases 2016-present Member of the Technical Biological Risk Committee of the IRD-Montpellier center 2015 Expert to the General Council of Essonne for the 2015 A.S.T.R.E call for projects 2014-present Member of jury for thesis grants (CBS2 UM doctoral school) 2012-present Member of Labex ParaFrap - Alliance Française against Parasitic Diseases 2009-2018 Member of the Languedoc-Roussillon Animal Testing Ethics Committee, 2008-2009 Representative of the IRD, appointed by Mr. JF. Girard, Working Group on Animal Experimentation of the National Academy of Medicine and the Academy of Sciences, coordinated by Mr. C. PILET. 2000-present Member of the French Society of Immunology C. Contributions to Science Recent contributions - Most relevant publications 1- Effective clinical management and success on control programs depend largely on early and accurate diagnosis. The rK39-based Rapid Diagnostic Tests (RDT) or ELISA became the most used tools. However, several studies reported variation of sensitivity depending on the endemic region, clinical form and Leishmania species involved. For cutaneous and mucocutaneous leishmaniasis diagnosis, serological tests are not commonly used because of their low sensitivity and variable specificity. This review highlights the growing interest in synthetic peptides used for serological diagnosis of leishmaniases, and their performances compared to some widely used tests with recombinant proteins. Peptide-based serological tests are promising as they could compensate for antigenic variability and improve performance, independently of Leishmania species and subspecies circulating in the endemic areas. Pagniez J, Petitdidier E, Parra-Zuleta O, Pissarra J, Bras-Gonçalves R. A systematic review of peptide-based serological tests for the diagnosis of leishmaniasis. Parasite. 2023; 30:10. doi: 10.1051/parasite/2023011. 2- This is the first proteomic analysis of the secretome comparing multiple Leishmania species, pathogenic and non-pathogenic to humans. The core secretome shared by all seven Leishmania species corresponded to about one-third of the total secreted proteins. Gene ontology annotation and enrichment analyses showed a high level of functional conservation among species. This study, focusing on conserved and species-specific secreted proteins, provides an important source of data for the discovery of antigens and biomarkers, and the development of vaccines, treatments, or diagnostics tools. Pissarra J, Pagniez J, Petitdidier E, Séveno M, Vigy O, Bras-Gonçalves R, Lemesre JL, Holzmuller P. Proteomic Analysis of the Promastigote Secretome of Seven Leishmania Species. J Proteome Res. 2022 ;21(1):30-48. doi: 10.1021/acs.jproteome.1c00244. 3- Peptide-based vaccine: the long multi-epitope peptides were able to activate human IFN-g producing CD4+ and CD8+ T-cells, both required for parasite elimination. Proof of concept for the efficacy of a peptide-based vaccine in a canine model. a. Hamrouni S, Bras-Gonçalves R, Kidar A, Aoun K, Chamakh-Ayari R, Petitdidier E, Messaoudi Y, Pagniez J, Lemesre JL, Meddeb-Garnaoui A. Design of multi-epitope peptides containing HLA class-I and class-II-restricted epitopes derived from immunogenic Leishmania proteins, and evaluation of CD4+ and CD8+ T cell responses induced in cured cutaneous leishmaniasis subjects. PLoS Negl Trop Dis. 2020 Mar;14(3):e0008093. b. Petitdidier E, Pagniez J, Pissarra J, Holzmuller P, Papierok G, Vincendeau P, Lemesre J, Bras-Gonçalves R. Peptide-based vaccine successfully induces protective immunity against canine visceral leishmaniasis. npj Vaccines. 2019 November 29; 4(1):49. 4- Several arguments in favor of the feasibility of a vaccine for the prevention of human leishmaniasis support the development objectives of such a vaccine. In humans, healing of leishmaniasis is usually associated with the development of long-lasting cellular immunity to reinfection (Bray and Modabber, 2000, Reithinger et al., 2007). In collaboration with our partners in the South (Tunisia, India, and Peru) and in Spain, our work has contributed to a better understanding of the underlying mechanisms involved in the induction of protective immune responses against leishmaniasis (Th1 / CD8 +), reinforcing the correlates of protection for the development of a vaccine for human use. a. Best I, Privat-Maldonado A, Cruz M, Zimic M, Bras-Gonçalves R, Lemesre JL, Arévalo J. IFN-γ Response Is Associated to Time Exposure Among Asymptomatic Immune Responders That Visited American Tegumentary Leishmaniasis Endemic Areas in Peru. Front Cell Infect Microbiol. 2018;8:289. b. Holzmuller P, Geiger A, Nzoumbou-Boko R, Pissarra J, Hamrouni S, Rodrigues V, Dauchy FA, Lemesre JL, Vincendeau P, Bras-Gonçalves R. Trypanosomatid Infections: How Do Parasites and Their Excreted-Secreted Factors Modulate the Inducible Metabolism of l-Arginine in Macrophages? Front Immunol. 2018;9:778. c. Kaushal H, Bras-Gonçalves R, Avishek K, Kumar Deep D, Petitdidier E, Lemesre JL, Papierok G, Kumar S, Ramesh V, Salotra P. Evaluation of cellular immunological responses in mono- and polymorphic clinical forms of post-kala-azar dermal leishmaniasis in India. Clin Exp Immunol. 2016 Jul;185(1):50-60. d. Kaushal H, Bras-Gonçalves R, Negi NS, Lemesre JL, Papierok G, Salotra P. Role of CD8(+) T cells in protection against Leishmania donovani infection in healed Visceral Leishmaniasis individuals. BMC Infect Dis. 2014 Dec 3;14:653. 5- This collaboration also demonstrated the antigenic properties of the Promastigote Surface Antigen (PSA) in humans, reinforcing its importance as a source of peptide-derivatives for a vaccine candidate. a. Petitdidier E, Pagniez J, Papierok G, Vincendeau P, Lemesre J, Bras-Gonçalves R. Recombinant Forms of Leishmania amazonensis Excreted/Secreted Promastigote Surface Antigen (PSA) Induce Protective Immune Responses in Dogs. PLOS Neglected Tropical Diseases. 2016; 10(5):e0004614. b. Bras-Gonçalves R, Petitdidier E, Pagniez J, Veyrier R, Cibrelus P, Cavaleyra M, Maquaire S, Moreaux J, Lemesre J. Identification and characterization of new Leishmania promastigote surface antigens, LaPSA-38S and LiPSA-50S, as major immunodominant excreted/secreted components of L. amazonensis and L. infantum. Infection, Genetics and Evolution. 2014 June; 24:1-14. c. Chamakh-Ayari R, Bras-Gonçalves R, Bahi-Jaber N, Petitdidier E, Markikou-Ouni W, Aoun K, Moreno J, Carrillo E, Salotra P, Kaushal H, Negi N, Arevalo J, Falconi-Agapito F, Privat A, Cruz M, Pagniez J, Papierok G, Rhouma F, Torres P, Lemesre J, Chenik M, Meddeb-Garnaoui A. In Vitro Evaluation of a Soluble Leishmania Promastigote Surface Antigen as a Potential Vaccine Candidate against Human Leishmaniasis. PLoS ONE. 2014; 9(5):e92708-. d. Lemesre J, Holzmuller P, Gonçalves R, Bourdoiseau G, Hugnet C, Cavaleyra M, Papierok G. Long-lasting protection against canine visceral leishmaniasis using the LiESAp-MDP vaccine in endemic areas of France: Double-blind randomised efficacy field trial. Vaccine. 2007 May; 25(21):4223-4234. Patents - Patent family: FR3081870A1 (2018); WO2019243018A1; EP3801608A1; US20210213114A1 ; BR112020024211A2 - Patent family: FR3014103A1 (2013); WO2015079420A2 - Patent family: FR3000402A1 (2012); WO2014102471A1; EP2938355A1; MA38298A1; BR112015015539A2 - Patent family: FR2881752A1 (2005); WO2006085011A1; US2009214595A1; CA2597512A1; EP1851316A1 D. Main grants - PL-VAC project - Funding agency: SATT AxLR Montpellier - Call “initial maturation” - project ID N°670. Grant allocated: 206 671€ (2019-2020); - EUROLEISH-NET project - Funding agency: EC H2020-MSCA-ITN-2014 – Grant ID: 642609. Grant allocated: 3 820 538€. (2015-2019); - "Polyvalent peptide vaccine for human use" project - Funding agency: IRD–Call for innovative project. Grant allocated: 33 500€. (2013-2014); - RAPSODI project - Funding agency: EC FP7-HEALTH-2.3.4-2- Grant ID: 223341. Grant allocated: 2 737 301€. (2009-2012); - VaxiLeish project - Funding agency: DGE-FUI-Competitiveness clusters - Grant ID: DGE-FUI-2006-1. Grant allocated: 3 307 081€. (2007-2009).

Domaines de recherche

Sciences du Vivant [q-bio]

Compétences

Immunology Parasitology Human health Diagnostic Vaccine Molecular biology

Publications

Image document

A systematic review of peptide-based serological tests for the diagnosis of leishmaniasis

Julie Pagniez , Elodie Petitdidier , Oriana Parra-Zuleta , Joana Pissarra , Rachel Bras-Gonçalves
Parasite, 2023, 30, ⟨10.1051/parasite/2023011⟩
Article dans une revue hal-04063404v1

Proteomic Analysis of the Promastigote Secretome of Seven Leishmania Species

Joana Pissarra , Julie Pagniez , Elodie Petitdidier , Martial Séveno , Oana Vigy
Journal of Proteome Research, 2022, 21 (1), pp.30-48. ⟨10.1021/acs.jproteome.1c00244⟩
Article dans une revue hal-03446765v1
Image document

Design of multi-epitope peptides containing HLA class-I and class-II-restricted epitopes derived from immunogenic Leishmania proteins, and evaluation of CD4+ and CD8+ T cell responses induced in cured cutaneous leishmaniasis subjects

Sarra Hamrouni , Rachel Bras-Gonçalves , Abdelhamid Kidar , Karim Aoun , Rym Chamakh-Ayari
PLoS Neglected Tropical Diseases, 2020, 14 (3), pp.e0008093. ⟨10.1371/journal.pntd.0008093⟩
Article dans une revue pasteur-03557433v1
Image document

Peptide-based vaccine successfully induces protective immunity against canine visceral leishmaniasis

Elodie Petitdidier , Julie Pagniez , Joana Pissarra , Philippe Holzmuller , Gérard Papierok
NPJ vaccines, 2019, 4, 9 p. ⟨10.1038/s41541-019-0144-2⟩
Article dans une revue hal-02618527v1
Image document

Trypanosomatid infections: How do parasites and their excreted-secreted factors modulate the inducible metabolism of L-arginine in macrophages?

Philippe Holzmuller , Anne Geiger , Romaric Nzoumbou-Boko , Joana Pissarra , Sarra Hamrouni
Frontiers in Immunology, 2018, 9, ⟨10.3389/fimmu.2018.00778⟩
Article dans une revue hal-02623664v1

Trypanosoma musculi infection in mice critically relies on mannose receptor-mediated arginase induction by a TbKHC1 kinesin H chain homolog

Romaric Nzoumbou-Boko , Géraldine de Muylder , Silla Semballa , Laurence Lecordier , Frédéric-Antoine Dauchy
Journal of Immunology, 2017, 199 (5), pp.1762-1771. ⟨10.4049/jimmunol.1700179⟩
Article dans une revue hal-02626915v1

Preclinical development of a new peptide-based vaccine against human leishmaniasis

J. Pissarra , Philippe Holzmuller , R. Bras-Goncalves , A. Garnaoui , J. L. Lemesre
Tropical Medicine and International Health, 2017, 22, pp.11
Article dans une revue hal-02617598v1
Image document

Recombinant forms of Leishmania amazonensis excreted/secreted promastigote surface antigen (PSA) induce protective immune responses in dogs

Elodie Petitdidier , Julie Pagniez , Gérard Papierok , Philippe Vincendeau , Jean-Loup Lemesre
PLoS Neglected Tropical Diseases, 2016, ⟨10.1371/journal.pntd.0004614⟩
Article dans une revue ird-01321775v1
Image document

Unravelling human trypanotolerance: IL8 is associated with infection control whereas IL10 and TNFα are associated with subsequent disease development

Hamidou Ilboudo , Rachel Bras-Gonçalves , Mamadou Camara , Laurence Flori , Oumou Camara
PLoS Pathogens, 2014, 10 (11), pp.1-11. ⟨10.1371/journal.ppat.1004469⟩
Article dans une revue hal-01193987v1
Image document

In Vitro Evaluation of a Soluble Leishmania Promastigote Surface Antigen as a Potential Vaccine Candidate against Human Leishmaniasis

Rym Chamakh-Ayari , Rachel Bras-Gonçalves , Narges Bahi-Jaber , Elodie Petitdidier , Wafa Markikou-Ouni
PLoS ONE, 2014, 9 (5), pp.e92708. ⟨10.1371/journal.pone.0092708⟩
Article dans une revue pasteur-01098532v1

Specific cpb copies within the Leishmania donovani complex: evolutionary interpretations and potential clinical implications in humans

M. Hide , R. Bras-Gonçalves , A. Bañuls
Parasitology, 2007, 134 (03), pp.379. ⟨10.1017/S0031182006001600⟩
Article dans une revue hal-03032664v1