Plasmodium falciparum Protein Microarray Antibody Profiles Correlate With Protection From Symptomatic Malaria in Kenya.

Abstract

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.

• Authors: Arlene E Dent, Rie Nakajima, Li Liang, Elisabeth Baum, Ann M Moormann, Peter Odada Sumba, John Vulule, Denise Babineau, Arlo Randall, D Huw Davies, Philip L Felgner, James W Kazura
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 212 Issue 9 Pg. 1429-38 (Nov 01 2015) ISSN: 1537-6613 [Electronic] United States
• PMID: 25883384 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Antibodies, Protozoan
• Antigens, Protozoan
• Antimalarials
• Immunoglobulin G
• Membrane Proteins
• Protozoan Proteins
• erythrocyte membrane protein 1, Plasmodium falciparum

Topics

• Adolescent
• Adult
• Aged
• Animals
• Antibodies, Protozoan (blood, immunology)
• Antigens, Protozoan (blood, immunology)
• Antimalarials (therapeutic use)
• Child
• Child, Preschool
• Female
• Humans
• Immunity, Innate
• Immunoglobulin G (blood)
• Infant
• Kenya
• Malaria (blood, drug therapy, immunology)
• Membrane Proteins (immunology)
• Merozoites (immunology)
• Mice
• Middle Aged
• Plasmodium falciparum (immunology, isolation & purification)
• Proportional Hazards Models
• Protein Array Analysis
• Protozoan Proteins (blood, genetics, immunology)
• Young Adult