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

Cole-Tobian, JL; Michon, P; Biasor, M; Richards, JS; Beeson, JG; Mueller, I; King, CL

Author(s): Cole-Tobian, JL; Michon, P; Biasor, M; Richards, JS; Beeson, JG; Mueller, I; King, CL;
Details: Publication Year 2009-09,Volume 77,Issue #9,Page 4009-4017
Journal Title: INFECTION AND IMMUNITY
Publication Type: Journal Article
Abstract: 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 the 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-kDa C-terminal region of P. vivax merozoite surface protein 1 (PvMSP1(19)), would have a delay in the time to reinfection following treatment to clear all blood-stage malaria infections. Ninety-four percent of the children were reinfected with P. vivax during biweekly follow-ups 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 the time to reinfection with the same variant of P. vivax by 25% compared to parasites expressing other PvDBPII alleles (age-adjusted hazard ratio, 0.75 [95% confidence interval, 0.56 to 1.00 by Cox regression]) and 39% lower incidence density parasitemia (P = 0.01). Two other prevalent alleles (AH and P) showed a similar trend of 16% and 18% protection, respectively, against parasites with the same PvDBPII allele and reduced incidence density parasitemia. Antibodies directed to PvDBPII PNG-P and -O were both associated with a 21 to 26% reduction in the risk of P. vivax infections with higher levels of parasitemia (>150 parasites/mu l), respectively. There was no association with high antibody levels to PvMSP1(19) and a delay in the time to P. vivax reinfection. Thus, anti-PvDBPII antibodies are associated with strain-specific immunity to P. vivax and support the use of PvDBPII for a vaccine against P. vivax.
Publisher: AMER SOC MICROBIOLOGY
Keywords: MEROZOITE SURFACE PROTEIN-1; C-TERMINAL REGIONS; INHIBITORY ANTIBODIES; IMMUNE-RESPONSES; LIGAND DOMAIN; MALARIA; INVASION; FALCIPARUM; EPIDEMIOLOGY; RECOGNITION
Publisher's Version: https://doi.org/10.1128/IAI.00158-09
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Creation Date: 2009-09-01 12:00:00