A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray.
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 approximately 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.
Crompton
Peter D
PD
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA. pcrompton@niaid.nih.gov
Kayala
Matthew A
MA
Traore
Boubacar
B
Kayentao
Kassoum
K
Ongoiba
Aissata
A
Weiss
Greta E
GE
Molina
Douglas M
DM
Burk
Chad R
CR
Waisberg
Michael
M
Jasinskas
Algis
A
Tan
Xiaolin
X
Doumbo
Safiatou
S
Doumtabe
Didier
D
Kone
Younoussou
Y
Narum
David L
DL
Liang
Xiaowu
X
Doumbo
Ogobara K
OK
Miller
Louis H
LH
Doolan
Denise L
DL
Baldi
Pierre
P
Felgner
Philip L
PL
Pierce
Susan K
SK
D000293:Adolescent; D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D006801:Humans; D007107:Immune System; D017780:Malaria Vaccines / Q000737:chemistry; D016778:Malaria, Falciparum / Q000276:immunology*; D008302:Mali; D010963:Plasmodium falciparum / Q000378:metabolism*; D040081:Protein Array Analysis / Q000379:methods*; D040901:Proteomics / Q000379:methods
D000953:Antigens, Protozoan; D017780:Malaria Vaccines