People living in areas where Plasmodium falciparum (Pf) and P. vivax (Pv) are endemic develop naturally acquired immunity to malaria blood stage infection and illness after repeated exposures to the parasite through childhood and adolescence. The rate at which this immunity develops is variable due to local differences in the intensity and temporal stability of transmission. A global effort is now underway to control and ultimately eliminate Pf and Pv through the use of vector interventions such as insecticidal bed nets. The goal of research proposed here is to identify novel and robust antibody assays to guide this effort. Probing a protein microarray containing 2,320 /^proteins with sera collected from Pf-exposed Malian children and adults indicated that long-lived antibody responses against hundreds of antigens are acquired after years of repeated /^infections and antibodies associated with protection were identified against 49 specific Pf antigens.^ Here we aim to extend these findings with a wortdwide sero-epidemiological analysis. This multi- ICEMR project will probe specimens from cross sectional and longitudinal studies in 5 regions around the world which differ in malaria transmission intensity and in Plasmodium species exposure. The array will contain 800 antigens from fYand Pv, and sera from the studies will be probed annually to determine the effect of vector control and chemoprevention on the development and decline ofthe serological response. This study will better our understanding of how naturally acquired immunity develops as a function of age and seasonal mosquito exposure. The data may also lead to the discovery of antibody biomarkers associated with parasite exposure and with protection from malarial disease.

Public Health Relevance

The study will determine antibody responses against 500 Pf and Pv antigens in cross sectional specimens collected from 5 different ICEMR locations around the wortd. To make results comparable between sites, harmonized cross sectional studies from the different sites will be age stratified between 2-25 years of age, and taken at 2 time points before and after the high transmission season for each location. Analysis of the specimens will also be harmonized by coordinating protein microarray probing and analysis through the Protein Microarray Laboratory at UC Irvine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
3U19AI089686-03S2
Application #
8477358
Study Section
Special Emphasis Panel (ZAI1-AWA-M (M1))
Project Start
Project End
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$250,000
Indirect Cost
$57,114
Name
Case Western Reserve University
Department
Type
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
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