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About

We have been using in vivo imaging and rodent malaria models to better understand the initial steps of malaria parasite infection in the tissues of the mammalian host. Imaging revealed novel steps in the parasite lifecycle in the skin and liver, the role of cell traversal activity in the progression of sporozoites through these tissues and how the parasite crosses the liver sinusoids avoiding the clearance by hepatic macrophages.

Skin phase of malaria infection

blood & lymph vessel invasion, search strategy to locate hotspots of intravasation

development inside skin cells

cell traversal in the dermis (1)  (2)

Kupffer cell evasion and crossing of liver sinusoids

merosome release

cell traversal in the liver

Our research group is now interested in identifying  specific determinants of host infection by plasmodial pre-erythrocytic (PE) stages, focused on the key factors involved in the elimination of these stages by the host immune system. We ultimately aim at the development of a modular, chimeric, multi-antigenic pre-clinical PE vaccine capable of sterilizing sporozoite infection. To achieve these goals our research program is based on three complementary axis of research briefly described below:

1. Determinants of host infection by malaria sporozoites

The first axis of our research program aims at scrutinizing the molecular determinants of infection in the skin and liver of the mammalian host. By using imaging, genetic, immunological and pharmacological approaches we intend to identify and characterize the molecules involved in three critical steps of sporozoite lifecycle: (a) the activation of motility in the dermis, (b) the search and subsequent invasion of cutaneous blood vessels, and (c) the specific arrest of parasites in the liver (in collaboration with the laboratory of Joana Tavares, IBMC, PT). Potential targets of neutralizing antibodies will be tested in the axis 3.

2. Determinants of host protection against PE stages

The second axis aims at the identification and characterization of antibodies and immune cells that can efficiently eliminate sporozoites and liver-stages in vivo. Recently, in collaboration with the laboratory of Silvia Boscardin (USP, BR),  we discovered that antibodies directed against the central repetitive region of the major surface protein of sporozoites, the circumsporozoite protein, directly kill P. yoelii, P. berghei and P. falciparum sporozoites without the necessity of downstream host effectors. These cytotoxic effectors are mainly associated with the neutralization of sporozoites in the host skin, but high-affinity and high-cytotoxicity antibodies also neutralize sporozoites in the liver. In collaboration with  Robert Seder (NIH, US), we are now assessing the correlation between cytotoxicity and protection in vivo using libraries of anti-P. falciparum CSP human monoclonal antibodies.

Regarding the elimination of infected hepatocytes by CD8+ T cells, in collaboration with the laboratories of Fidel Zavala (JHMRI, US) and Katsuyuki Yui (Nagasaki University, JP), we discovered that antigen specific CD8+ T cells recruit other specific and non-specific immune cells to eliminate liver-stages by forming an antigen-driven inflammatory infiltrate around  infected hepatocytes. The protective role of non-specific cells recruited to these cellular foci is being assessed, and tested as a complementary way to enhance protection. The generation of these optimal protective effectors is also driving the design of antigens in the axis 3.

3. Pre-clinical development of a multi-antigenic PE vaccine

The third axis of our research program aims at developing chimeric and modular antigens composed by the fusion of protective domains of multiple protective antigens conserved among plasmodial species. In collaboration with the laboratory of Pierre Charneau (Institut Pasteur) we are using lentiviral delivery to identify protective antigens/ domains in vivo and combine them as individual antigens or chimeric fusions. So far, we have identified 8 conserved protective antigens, which when combined sterile protects the vast majority of immunized mice against P. berghei sporozoite challenge. In collaboration with Georges Snounou and Roger LeGrand (CEA, FR), the protective activity of these antigens/ fusions will be assessed using a non-human primate infecting plasmodial species, before ultimately being tested in humans.

Former Members

2000
2000
Name
Position
2015
2019
Mohammed Bellafquih
2015
2019
Chetan Aditya
PhD Student
2015
2019
Hang Zhong
2015
2019
Jennifer Pham
Technician
2015
2019
Sabine Thiberge
Research Engineer
2015
2019
Vanessa Lagal
Post-doc
2015
2016
Corinne Kanakis
Administrative Staff
2015
2020
Robert Menard
Permanent Researcher
2015
2021
Eduardo Aliprandini
Post-doc
2016
2016
Clyde Carridin
Student
2016
2016
Abdouramane Camara
Graduate Student
2016
2016
Théo Rossignol
High School Student
2016
2017
Dina Moustafa Abouraya Katry
Post-doc
2017
2017
Ceylia Dupin
High School Student
2017
2017
Clovis Nicodeme Gatsi
Undergraduate Student
2017
2018
Pablo Conde Benoits
Graduate Student
2017
2018
Camila Fabbri
OREX PhD Student
2017
2018
Franz Kahlich
Graduate Student
2017
2023
Pauline Formaglio
Post-doc
2018
2018
Paul Cayrou
High School Student
2018
2018
Nathaniel Lecian Dale
Undergraduate Student
2018
2018
Matthieu Lallement
Engineer Student
2018
2019
Rocio Rubio Bodi
Undergraduate Student
2018
2019
Rodolfo Ferreira Marques
OREX PhD Student
2018
2019
Olga Pacios Santamaria
Graduate Student
2019
2019
Luc Bourbon
Graduate Student
2019
2020
David Alexandre Mendes Da Costa
OREX PhD Student
2020
2020
Benjamin Bouchoucha
High School Student
2020
2021
Monica Da Silva Sa
OREX PhD Student
2021
2021
June Verhaak
Graduate Student
2021
2021
Ana Rafaela Azevedo Teixeira
OREX PhD Student
2021
2021
Guillaume Malrieu
Undergraduate Student
2021
2022
Corinna Perschbacher
Graduate Student
2021
2023
Lisa Verzier
Post-doc
2022
2022
Rima Belfali
High School Student
2022
2022
Belsy del Carmen Valeriano Alegria
Graduate Student
2022
2023
Margaux Chauvet
Engineer
2023
2023
Rébecca Houenou
High School Student
2023
2023
Sandra Marin
Engineer Student
2023
2024
Xiomara Gaitan
OREX PhD Student
2023
2024
Reina Okada
Graduate Student
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Contact

Phone: 01 4568 8273 Email: rogerio.amino@pasteur.fr Address 25-28 Rue du Docteur Roux 75015, Paris France. Sergent building n° 25, 2nd floor, left side, office n° 09 B Phone: 01 40 61 39 91 (Assistant) maryse.brandt@pasteur.fr Sergent building n° 25, 5th floor, left side, office n° 06