Malaria caused by Plasmodium falciparum is a major public health problem. Millions die each year, mostly children and pregnant women. Infants, after losing the protection provided by passively acquired maternal Abs become susceptible to infection and disease. In endemic areas, infants become infected sometime in the 1st year and begin to develop their own immunity. Thus, longitudinal studies in infants provide an opportunity to assess the importance of Abs to specific malarial Ags as the infants rapidly change from resistant to susceptible to developing immunity. Little is known about this process. As only small amounts of blood can be repeatedly collected from infants, it has been impossible to study responses to multiple Ags. The innovative flow-based suspension array technology (SAT) provides an approach to do these studies. SAT is a quantitative indirect immunoassay that allows simultaneous measurement of Abs to multiple Ags, each coated to fluorospheres of different intensities. The overall aim of our parent grant is to identify tests that correlate with protective immunity to P. falciparum disease. Using ELISA, Abs to only two malarial Ags can be measured since only small amounts of blood can be collected. While the two Ags selected are important, Abs to Ags other than those being studied are implicated in protection to P. falciparum disease. Accordingly, the aim of this proposal is to develop and validate a test for measuring Abs to a panel of malarial Ags using the innovative SAT approach and to use this malarial Ag array to test the following hypotheses: 1) Infants who have high levels of maternal Abs at delivery to one or more of the Ags being tested will develop their first clinical episode later in life than infants born with low/no Abs to these Ags. 2) Infants who, following infection, produce Abs to one or more of the Ags being tested will have fewer malaria episodes between 6-12 months than infants who do not. Analysis of Abs to a panel of candidate Ags will provide greater potential to identify """"""""correlates"""""""" of protection compared with our original proposal. In addition, validation of a SAT assay using a panel of functionally relevant malarial Ags would provide an important tool for the malaria research and vaccine development fields as well as expand the scope and potential of our parent study.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI053798-02
Application #
6661982
Study Section
Special Emphasis Panel (ZRG1-MBC-1 (01))
Program Officer
Naficy, Abdollah B
Project Start
2002-09-30
Project End
2006-08-31
Budget Start
2003-09-01
Budget End
2006-08-31
Support Year
2
Fiscal Year
2003
Total Cost
$232,800
Indirect Cost
Name
Georgetown University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
Fouda, Genevieve G; Leke, Rose F G; Long, Carole et al. (2006) Multiplex assay for simultaneous measurement of antibodies to multiple Plasmodium falciparum antigens. Clin Vaccine Immunol 13:1307-13