Malaria

Deepak Gaur, Chetan Chitnis and Virander Chauhan of the International Centre for Genetic Engineering & Biotechnology in India will attempt to develop a blood- stage malaria vaccine that uses a combination of two proteins found among a wide diversity of malaria parasites. Their goal is to stimulate antibodies that would stop parasite infection of red blood cells by blocking multiple pathways of invasion.

Rajan George of Paladin Biosciences, a division of Paladin Labs Inc. in Canada will produce a vaccine with multiple malaria antigens to target dendritic cell receptors and without the need for an adjuvant, in an effort to induce both antibody and cell-mediated immune responses to the malaria parasite at various stages of the infection.

Krystal Evans of The Walter and Eliza Hall Institute in Australia will knock out several proteins that support the expression of the major virulence factor for the malaria parasite. Their aim is create a genetically-attenuated live malaria vaccine that elicits a strong immune response against diverse strains of the parasite.

Nirbhay Kumar of Johns Hopkins University in the U.S. will use a technique called codon harmonization to fully and correctly express a complex malaria gamete surface protein. The sexual stages of malaria parasites have been shown to be particularly vulnerable to antibody targeting. This approach may be able to block the transmission of malaria in insect vectors.

Kailash Patra of the University of California, San Diego in the U.S. will use proteomics to examine gametocyte, zygote, or ookinete surface proteins of the malaria parasite to test their reactivity to human serum collected from malaria endemic regions, and to identify new antigen candidates for malaria vaccines.

William Gordon and collaborators at Tetragenetics, Inc. in the U.S. propose using T. thermophilia, a fresh-water protozoa commonly used in basic research, to produce malaria antigens in a crystalline protein gel. The close evolutionary relationship between T. thermophilia and protozoan malaria parasites may allow the antigens to retain their natural conformation. In this way, multiple vaccine components can be readily harvested as a single, low-cost, high-potency vaccine formulation. This project's Phase I research demonstrated that T.

Chang Yi Wang of United Biomedical, Inc. in the United States will develop and test synthetic peptide immunogens that mimic conserved sites used by HIV to gain entry to host T-cells. Mimicking the correct three-dimensional structure of these important proteins should generate antibody responses that block this initial step of HIV infection and neutralize the virus.

Jacquin Niles of the Massachusetts Institute of Technology in the U.S. is developing a method to switch individual genes on and off in the malaria-causing parasite Plasmodium falciparum for evaluating candidate and existing antimalarial drugs. In Phase I, they built and tested a scalable TetR-aptamer system for rapidly and easily manipulating gene expression in the parasite genome, and showed that it could be used to validate the target of a 4-aminoquinoline antimalarial drug.

Michael Klemba of Virginia Polytechnic Institute and State University in the U.S. will identify anti-malarial compounds from the Malaria Box that function as inhibitors of the cytostomal endocytic pathway used by the malaria parasite P. falciparum to internalize host erythrocyte proteins. Characterizing the molecular mechanisms of this process could lead to the discovery of new anti-malarial compounds.

Daniel Irimia and Anh Hoang of Massachusetts General Hospital in the U.S. seek to develop a microfluidic device that can be used to screen anti-malarial drugs for the development of drug resistance with single cell resolution. The device will be validated using a subset of anti-malarial compounds from the Malaria Box. The ability to monitor single cells for resistance will greatly reduce the time needed to screen drugs for acquired resistance, allowing for much earlier and more accurate assessment of effective drugs to control and eradicate malaria.