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Project #3564
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#3564 : Mining the Plasmodium genome to identify novel blood stage antigens for use as malaria vaccine candidates
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Name of Applicant : Chetan Chitnis
Date of application : 09-02-2016
Unit : Malaria Parasite Biology and Vaccines
Location : 25-05-06A
Phone : 1 44 38 94 28
@ Mail : chetan.chitnis@pasteur.fr

Project context and summary :

Malaria remains a major problem in many tropical countries with Plasmodium falciparum accounting for up to 1 million deaths, primarily in infants and children residing in endemic areas of sub-Saharan Africa. P. vivax, the other important species for human malaria is geographically more widespread and causes 80-100 million cases of malaria each year. All the pathology related to malaria is attributed to the blood stage of the parasite life cycle during which Plasmodium merozoites invade and multiply within host erythrocytes. We are interested in understanding the process of RBC invasion by malaria parasites at the molecular level with the goal of blocking their interaction with antibodies to inhibit invasion and kill the parasite. The first generation of recombinant blood stage malaria vaccine candidates based on antigens such as the merozoite surface protein (MSP1) and apical merozoite antigen-1 (AMA01) have been tested in field trials and failed to provide any efficacy against P. falciparum malaria. There is thus an urgent need to identify novel parasite antigens that play a role in invasion and can serve as vaccine candidates that elicit strong antibody responses that block blood stage parasite growth. In this project, we propose to mine the P. falciparum and P. vivax genome databases using bio-informatic tools to identify potential, novel blood stage invasion related parasite antigens that can serve as potential candidates for blood stage malara vaccines. Criteria such as expression profile, presence of conserved domains in orthologs from related plasmodium species, limited polymorphisms in field isolates, interaction with other invasion related proteins and localization to apical organelles or merozoite surface will be used to interrogate P. falciparum and P. vivax genome sequence data and identify potential invasion related antigens that will be selected for validation as vaccine candidates for malaria.


Related team publications :
Dawn A, Singh S, More KR, Siddiqui FA, Pachikara N, Ramdani G, Langsley G and Chitnis CE. The central role of cAMP in regulating Plasmodium falciparum merozoite invasion of human erythrocytes. 2014. PLoS Pathogens. 10(12):e1004520. 4. Chitnis CE, Mukherjee P, Mehta S, Yazdani SS, Dhawan S, Shakri AR, Bharadwaj R, Gupta PK, Hans D, Mazumdar S, Singh B Kumar S, Pandey G, Parulekar V, Imbault N, Shivyogi P, Godbole G, Mohan K, Leroy O, Singh K, Chauhan VS. 2015.
Chitnis CE, Mukherjee P, Mehta S, Yazdani SS, Dhawan S, Shakri AR, Bharadwaj R, Gupta PK, Hans D, Mazumdar S, Singh B Kumar S, Pandey G, Parulekar V, Imbault N, Shivyogi P, Godbole G, Mohan K, Leroy O, Singh K, Chauhan VS. 2015. Phase I clinical trial of a recombinant blood stage vaccine candidate for Plasmodium falciparum malaria based on MSP1 and EBA175. PLoS One. 0(4):e0117820.
Reddy KS, Pandey AK, Singh H, Sahar T, Emmanuel A, Chitnis CE, Chauhan VS, Gaur D. Bacterially expressed full-length recombinant Plasmodium falciparum RH5 protein binds erythrocytes and elicits potent strain-transcending parasite-neutralizing antibodies. 2014. Infect Immun. 82:152-64.
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Status : Pending


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