A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray

Crompton, Peter D., Kayala, Matthew A., Traore, Boubacar, Kayentao, Kassoum, Ongoiba, Aissata, Weiss, Greta E., Molina, Douglas M., Burk, Chad R., Waisberg, Michael, Jasinskas, Algis, Tan, Xiaolin, Doumbo, Safiatou, Doumtabe, Didier, Kone, Younoussou, Narum, David L., Liang, Xiaowu, Doumbo, Ogobara K., Miller, Louis H., Doolan, Denise L., Baldi, Pierre, Felgner, Philip L., and Pierce, Susan K. (2010) A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray. Proceedings of the National Academy of Sciences, 107 (15). pp. 6958-6963.

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Abs are central to malaria immunity, which is only acquired after years of exposure to Plasmodium falciparum (Pf). Despite the enormous worldwide burden of malaria, the targets of protective Abs and the basis of their inefficient acquisition are unknown. Addressing these knowledge gaps could accelerate malaria vaccine development. To this end, we developed a protein microarray containing ∼23% of the Pf 5,400-protein proteome and used this array to probe plasma from 220 individuals between the ages of 2–10 years and 18–25 years in Mali before and after the 6-month malaria season. Episodes of malaria were detected by passive surveillance over the 8-month study period. Ab reactivity to Pf proteins rose dramatically in children during the malaria season; however, most of this response appeared to be short-lived based on cross-sectional analysis before the malaria season, which revealed only modest incremental increases in Ab reactivity with age. Ab reactivities to 49 Pf proteins measured before the malaria season were significantly higher in 8–10-year-old children who were infected with Pf during the malaria season but did not experience malaria (n = 12) vs. those who experienced malaria (n = 29). This analysis also provided insight into patterns of Ab reactivity against Pf proteins based on the life cycle stage at which proteins are expressed, subcellular location, and other proteomic features. This approach, if validated in larger studies and in other epidemiological settings, could prove to be a useful strategy for better understanding fundamental properties of the human immune response to Pf and for identifying previously undescribed vaccine targets.

Item ID: 42723
Item Type: Article (Research - C1)
ISSN: 1091-6490
Keywords: antigen discovery; naturally acquired immunity; Plasmodium falciparum; malaria; prospective cohort study; Mali
Funders: National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), National Science Foundation (NSF), Pfizer Australia Senior Research Fellow (PASRF)
Projects and Grants: NIAID Grant 1R43AI066791, NIH Biomedical Informatics Training Grant LM-07443-01, NSF EIA-0321390, NSF IIS-0513376
Date Deposited: 17 Mar 2016 05:09
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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