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Infection and Immunity, September 2009, p. 4009-4017, Vol. 77, No. 9
0019-9567/09/$08.00+0 doi:10.1128/IAI.00158-09
Copyright © 2009, American Society for Microbiology. 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,1,2
Pascal Michon,3
Moses Biasor,3
Jack S. Richards,4
James G. Beeson,4
Ivo Mueller,3 and
Christopher L. King1,2*
Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio,1 Veterans Affairs Research Service, Cleveland, Ohio,2 Papua New Guinea Institute for Medical Research, Goroka, Papua New Guinea,3 The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia4
Received 10 February 2009/ Returned for modification 23 March 2009/ Accepted 22 June 2009
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 (PvMSP119), 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/µl), respectively. There was no association with high antibody levels to PvMSP119 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.
* Corresponding author. Mailing address: Center for Global Health and Diseases, Case Western Reserve University, Wolstein Research Building, Room 4132, 2301 Cornell Rd., Cleveland, OH 44106. Phone: (216) 368-4817. Fax: (216) 368-4825. E-mail: cxk21{at}case.edu
Published ahead of print on 29 June 2009.
Infection and Immunity, September 2009, p. 4009-4017, Vol. 77, No. 9
0019-9567/09/$08.00+0 doi:10.1128/IAI.00158-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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