Malaria Parasite Receptors And Host Cell Ligands

Miller, Louis

Abstract

Accomplishments during the year: 1. The sialic acid binding site has been modeled for BAEBL, identifying requirements for sialic acid binding. 2. The immune response to RH4 has been studied. This work continues to expand our understanding of parasite invasion of red cells by identifying the receptors and ligands and determining the potential of these targets for vaccine development. We show that recombinant P. falciparum RH 4 can block invasion but antibodies to PfRH4 cannot block invasion. 3. Begun to study viable merozoites during invasion to follow the moving junction and the effect of anti-AMA1 on invasion. 4. Study the changes in the histone modifications of nucleosomes of RH4 and PEBL to correlate with the change of expression in Dd2 to Dd2/nm. 5. Begun to study the cytoplasmic domains of molecules in the moving junction to determine if they bind to aldolase or other molecules that bind actin. 5. Study the role of RH1 and RH2 as targets for vaccine development.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000241-27
• Application #: 7732429
• Support Year: 27
• Fiscal Year: 2008
• Total Cost: $474,061

Institution

• Name: National Institute of Allergy and Infectious Diseases
• Country: United States

Publications

Mayer, D C Ghislaine; Cofie, Joann; Jiang, Lubin et al. (2009) Glycophorin B is the erythrocyte receptor of Plasmodium falciparum erythrocyte-binding ligand, EBL-1. Proc Natl Acad Sci U S A 106:5348-52

Beaty, Barry J; Prager, Denis J; James, Anthony A et al. (2009) From tucson to genomics and transgenics: the vector biology network and the emergence of modern vector biology. PLoS Negl Trop Dis 3:e343

Qian, Feng; Rausch, Kelly M; Muratova, Olga et al. (2008) Addition of CpG ODN to recombinant Pseudomonas aeruginosa ExoProtein A conjugates of AMA1 and Pfs25 greatly increases the number of responders. Vaccine 26:2521-7

Miura, Kazutoyo; Orcutt, Andrew C; Muratova, Olga V et al. (2008) Development and characterization of a standardized ELISA including a reference serum on each plate to detect antibodies induced by experimental malaria vaccines. Vaccine 26:193-200

Dicko, Alassane; Sagara, Issaka; Ellis, Ruth D et al. (2008) Phase 1 study of a combination AMA1 blood stage malaria vaccine in Malian children. PLoS ONE 3:e1563

Huaman, Maria Cecilia; Martin, Laura B; Malkin, Elissa et al. (2008) Ex vivo cytokine and memory T cell responses to the 42-kDa fragment of Plasmodium falciparum merozoite surface protein-1 in vaccinated volunteers. J Immunol 180:1451-61

Wu, Yimin; Ellis, Ruth D; Shaffer, Donna et al. (2008) Phase 1 trial of malaria transmission blocking vaccine candidates Pfs25 and Pvs25 formulated with montanide ISA 51. PLoS ONE 3:e2636

Mullen, Gregory E D; Ellis, Ruth D; Miura, Kazutoyo et al. (2008) Phase 1 trial of AMA1-C1/Alhydrogel plus CPG 7909: an asexual blood-stage vaccine for Plasmodium falciparum malaria. PLoS ONE 3:e2940

Gaur, Deepak; Singh, Sanjay; Singh, Subhash et al. (2007) Recombinant Plasmodium falciparum reticulocyte homology protein 4 binds to erythrocytes and blocks invasion. Proc Natl Acad Sci U S A 104:17789-94

Singh, Subhash; Plassmeyer, Matthew; Gaur, Deepak et al. (2007) Mononeme: a new secretory organelle in Plasmodium falciparum merozoites identified by localization of rhomboid-1 protease. Proc Natl Acad Sci U S A 104:20043-8