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Author Notes:

Correspondence: E-mail: d.stanisic@griffith.edu.au (DIS); ivomueller@fastmail.fm (IM)

Danielle I. Stanisic and Sarah Javati contributed equally to this work.

Conceived and designed the experiments: DIS MRG IM.

Performed the experiments: DIS SJ BK EL CK.

Analyzed the data: DIS IM.

Contributed reagents/materials/analysis tools: JJ BS EVSM PS IF.

Wrote the paper: DIS SJ MRG IM.

We would like to thank all study participants and their families and the field teams at the Institute of Medical Research.

We would also like to thank Moses Lagog and Anselm Masalan for assistance with sample processing.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The authors have declared that no competing interests exist.


Research Funding:

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).

IM is supported by an NHMRC Senior Research Fellowship (Grant no. 1043345).

This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Infectious Diseases
  • Parasitology
  • Tropical Medicine
  • Plasmodium
  • Antibodies
  • Malaria
  • Malarial parasites
  • Merozoites
  • Vaccines
  • Parasitic diseases
  • Antibody response

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

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Journal Title:

PLoS Neglected Tropical Diseases


Volume 7, Number 11


, Pages e2498-e2498

Type of Work:

Article | Final Publisher PDF


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.

Copyright information:

© 2013 Stanisic et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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