Plasmodium falciparum Protein Microarray Antibody Profiles Correlate With Protection From Symptomatic Malaria in Kenya
Center for Global Health Research; Program in Molecular Medicine
Adolescent; Adult; Aged; Animals; Antibodies, Protozoan; Antigens, Protozoan; Antimalarials; Child; Child, Preschool; Female; Humans; Immunity, Innate; Immunoglobulin G; Infant; Kenya; Malaria; Membrane Proteins; Merozoites; Mice; Middle Aged; Plasmodium falciparum; Proportional Hazards Models; *Protein Array Analysis; Protozoan Proteins; Young Adult
Immunity | Immunology of Infectious Disease | Infectious Disease | Parasitic Diseases | Parasitology
BACKGROUND: Immunoglobulin G antibodies (Abs) to Plasmodium falciparum antigens have been associated with naturally acquired immunity to symptomatic malaria.
METHODS: We probed protein microarrays covering 824 unique P. falciparum protein features with plasma from residents of a community in Kenya monitored for 12 weeks for (re)infection and symptomatic malaria after administration of antimalarial drugs. P. falciparum proteins recognized by Abs from 88 children (aged 1-14 years) and 86 adults (aged > /= 18 years), measured at the beginning of the observation period, were ranked by Ab signal intensity.
RESULTS: Abs from immune adults reacted with a total 163 of 824 P. falciparum proteins. Children gradually acquired Abs to the full repertoire of antigens recognized by adults. Abs to some antigens showed high seroconversion rates, reaching maximal levels early in childhood, whereas others did not reach adult levels until adolescence. No correlation between Ab signal intensity and time to (re)infection was observed. In contrast, Ab levels to 106 antigens were significantly higher in children who were protected from symptomatic malaria compared with those who were not. Abs to antigens predictive of protection included P. falciparum erythrocyte membrane protein 1, merozoite surface protein (MSP) 10, MSP2, liver-stage antigen 3, PF70, MSP7, and Plasmodium helical interspersed subtelomeric domain protein.
CONCLUSIONS: Protein microarrays may be useful in the search for malaria antigens associated with protective immunity.
antibody, antigen, malaria, protective immunity, protein microarray
DOI of Published Version
J Infect Dis. 2015 Nov 1;212(9):1429-38. doi: 10.1093/infdis/jiv224. Epub 2015 Apr 15. Link to article on publisher's site
The Journal of infectious diseases
Dent, Arlene E.; Nakajima, Rie; Liang, Li; Baum, Elisabeth; Moormann, Ann M.; Sumba, Peter Odada; Vulule, John; Babineau, Denise; Randall, Arlo; Davies, D. Huw; Felgner, Philip L.; and Kazura, James W., "Plasmodium falciparum Protein Microarray Antibody Profiles Correlate With Protection From Symptomatic Malaria in Kenya" (2015). University of Massachusetts Medical School Faculty Publications. 885.