IAI Accepts, published online ahead of print on 29 June 2009

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Infect. Immun. doi:10.1128/IAI.00158-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Strain-Specific Duffy Binding Protein Antibodies Correlate with Protection Against Infection with Homologous Compared to Heterologous Plasmodium vivax Strains in Papua New Guinean Children

Jennifer L. Cole-Tobian, Pascal Michon, Moses Biasor, Jack S. Richards, James G. Beeson, Ivo Mueller, and Christopher L. King^*

Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH, USA; Veterans Affairs Research Service, Cleveland, OH; Papua New Guinea Institute for Medical Research, Goroka, Papua New Guinea; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia

^* To whom correspondence should be addressed. Email: cxk21{at}case.edu.

Individuals repeatedly infected with malaria acquire protection from infection and disease; immunity is thought to be primarily antibody-mediated and directed to blood stage infection. Merozoite surface proteins involved in invasion of host erythrocytes are likely targets of protective antibodies. We hypothesized that Papua New Guinean children (N=206) who acquire high antibody levels to two Plasmodium vivax merozoite proteins, Duffy binding protein region II (PvDBPII) and the 19-kD C-terminal region of P. vivax merozoite surface protein 1 (PvMSP1₁₉) would have a delay in time to re-infection following treatment to clear all blood stage malaria infections. 94% of the children were re-infected with P. vivax during biweekly follow-up for 6 months. Since PvDBPII is polymorphic, we examined whether individuals acquired strain-specific immunity to PvDBPII. Children with high antibody levels to a prevalent PvDBPII allele (O) were associated with a delay in time to re-infection with the same variant of P. vivax by 25% compared to parasites expressing other PvDBPII alleles (age Adjusted Hazard Ratio = 0.75 (0.56-1.00, 95% CI, Cox Regression) and 39% lower incidence density parasitema (P=0.01). Two other prevalent alleles (AH and P) showed a similar trend of 16% and 18% protection against parasites with same PvDBPII allele and reduced incidence-density parasitemia. Antibodies directed to PvDBPII PNG-P and O were both associated with a 21-26% reduction in risk of P. vivax infections with higher parasitemia (>150 parasites/µl), respectively. There was no association with high antibody levels to PvMSP1₁₉ and delay in time to P. vivax re-infection. Thus, anti-PvDBPII antibodies are associated with strain-specific immunity to P. vivax and support use of PvDBPII for a vaccine against P. vivax.