Abstract

The long-term goal of this research is to understand the immune basis of acquired resistance to pre-erythrocytic stages of Plasmodium falciparum in humans. Studies done by ourselves and others suggest that T cell INF-y responses to selected vaccine candidate molecules mediate or are a surrogate of resistance against liver-stage P. faIciparum.
Specific aims to determine the relevance of these responses to protection against hepatic-stage parasites are: 1. To characterize the repertoire of HLA class 1-restricted epitopes for the vaccine candidate molecules LSA-1 and TRAP in resident of a holoendemic area in the Wosera, Papua New Guinea. 2. To determine whether CD4, CD8, and CTL responses to TRAP and LSA-l epitopes are predictive of susceptibility to infection in partially resistance adults and increase with age in l to 3 year old children. 3. To evaluate the contribution of parasite allelic variation to heterogeneity of T cell responses in humans. Knowledge of these aspects of human immunity will facilitate development and evaluation of a human malaria vaccine.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI036478-06
Application #
2886940
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Program Officer
Hall, B Fenton
Project Start
1994-09-15
Project End
2001-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
6
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106

  Publications

Mehlotra, Rajeev K; Henry-Halldin, Cara N; Zimmerman, Peter A (2009) Application of pharmacogenomics to malaria: a holistic approach for successful chemotherapy. Pharmacogenomics 10:435-49
Mehlotra, Rajeev K; Mattera, Gabriel; Bockarie, Moses J et al. (2008) Discordant patterns of genetic variation at two chloroquine resistance loci in worldwide populations of the malaria parasite Plasmodium falciparum. Antimicrob Agents Chemother 52:2212-22
Karl, Stephan; David, Makindi; Moore, Lee et al. (2008) Enhanced detection of gametocytes by magnetic deposition microscopy predicts higher potential for Plasmodium falciparum transmission. Malar J 7:66
Kasehagen, Laurin J; Mueller, Ivo; Kiniboro, Benson et al. (2007) Reduced Plasmodium vivax erythrocyte infection in PNG Duffy-negative heterozygotes. PLoS One 2:e336
Mehlotra, Rajeev K; Bockarie, Moses J; Zimmerman, Peter A (2007) CYP2B6 983T>C polymorphism is prevalent in West Africa but absent in Papua New Guinea: implications for HIV/AIDS treatment. Br J Clin Pharmacol 64:391-5
Mehlotra, Rajeev K; Ziats, Mark N; Bockarie, Moses J et al. (2006) Prevalence of CYP2B6 alleles in malaria-endemic populations of West Africa and Papua New Guinea. Eur J Clin Pharmacol 62:267-75
Mehlotra, Rajeev K; Mattera, Gabriel; Bhatia, Kuldeep et al. (2005) Insight into the early spread of chloroquine-resistant Plasmodium falciparum infections in Papua New Guinea. J Infect Dis 192:2174-9
Patel, Sheral S; King, Christopher L; Mgone, Charles S et al. (2004) Glycophorin C (Gerbich antigen blood group) and band 3 polymorphisms in two malaria holoendemic regions of Papua New Guinea. Am J Hematol 75:1-5
Zimmerman, Peter A; Patel, Sheral S; Maier, Alexander G et al. (2003) Erythrocyte polymorphisms and malaria parasite invasion in Papua New Guinea. Trends Parasitol 19:250-2
Maier, Alexander G; Duraisingh, Manoj T; Reeder, John C et al. (2003) Plasmodium falciparum erythrocyte invasion through glycophorin C and selection for Gerbich negativity in human populations. Nat Med 9:87-92

Showing the most recent 10 out of 20 publications