Naturally Acquired Immune Responses to P. vivax Merozoite Surface Protein 3 alpha and Merozoite Surface Protein 9 Are Associated with Reduced Risk of P. vivax Malaria in Young Papua New Guinean Children

• Type of Material: Article
• Authors: Danielle I. Stanisic, Walter and Eliza Hall Institute; Sarah Javati, Papua New Guinea Institute of Medical Research; Benson Kiniboro, Papua New Guinea Institute of Medical Research; Enmoore Lin, Papua New Guinea Institute of Medical Research; Jianlin Jiang, Emory University; Balwan Singh, Emory University; Esmeralda Meyer, Emory University; Peter Siba, Papua New Guinea Institute of Medical Research; Cristian Koepfli, Walter and Eliza Hall Institute; Ingrid Felger, Swiss Tropical Institute and Public Health Institute; Mary Galinski, Emory University; Ivo Mueller, Walter and Eliza Hall Institute
• Language: English
• Date: 2013-11
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Stanisic et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pntd.0002498
• Title of Journal or Parent Work: PLoS Neglected Tropical Diseases
• ISSN: 1935-2727
• Volume: 7
• Issue: 11
• Start Page: e2498
• End Page: e2498
• Grant/Funding Information: IM is supported by an NHMRC Senior Research Fellowship (Grant no. 1043345).; This work was supported by the National Institutes of Health (AI063135), the Australian Agency for International Development (AusAID) and the National Health and Medical Research Council (Grant no. 516735).; This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS.
• Keywords: Infectious Diseases; ANTIBODIES; Parasitology; PLASMODIUM-VIVAX; INFECTION; IN-VITRO; Antibody response; PROTECTION; Merozoites; BLOOD MONOCYTES; Malaria; Parasitic diseases; DUFFY-BINDING-PROTEIN; TROPICAL MEDICINE; PARASITOLOGY; Malarial parasites; Tropical Medicine; Antibodies; INHIBIT PARASITE GROWTH; Vaccines; DIVERSITY; FALCIPARUM-MALARIA; Plasmodium; Life Sciences & Biomedicine; Science & Technology
• Research Categories: Health Sciences, Immunology; Health Sciences, Public Health

Abstract

Background:Plasmodium vivax is the most geographically widespread human malaria parasite. Cohort studies in Papua New Guinea have identified a rapid onset of immunity against vivax-malaria in children living in highly endemic areas. Although numerous P. vivax merozoite antigens are targets of naturally acquired antibodies, the role of many of these antibodies in protective immunity is yet unknown.Methodology/Principal Findings:In a cohort of children aged 1-3 years, antibodies to different regions of Merozoite Surface Protein 3α (PvMSP3α) and Merozoite Surface Protein 9 (PvMSP9) were measured and related to prospective risk of P. vivax malaria during 16 months of active follow-up. Overall, there was a low prevalence of antibodies to PvMSP3α and PvMSP9 proteins (9-65%). Antibodies to the PvMSP3α N-terminal, Block I and Block II regions increased significantly with age while antibodies to the PvMSP3α Block I and PvMSP9 N-terminal regions were positively associated with concurrent P. vivax infection. Independent of exposure (defined as the number of genetically distinct blood-stage infection acquired over time ( mol FOB)) and age, antibodies specific to both PvMSP3α Block II (adjusted incidence ratio (aIRR) = 0.59, p = 0.011) and PvMSP9 N-terminus (aIRR = 0.68, p = 0.035) were associated with protection against clinical P. vivax malaria. This protection was most pronounced against high-density infections. For PvMSP3α Block II, the effect was stronger with higher levels of antibodies.Conclusions:These results indicate that PvMSP3α Block II and PvMSP9 N-terminus should be further investigated for their potential as P. vivax vaccine antigens. Controlling for mol FOB assures that the observed associations are not confounded by individual differences in exposure.