- Introduction
- Materials and Methods
- Recruitment of P. vivax-exposed and -naïve donors.
- Screening of sera by enzyme-linked immunosorbent assay and immunofluorescent assays to assess reactivity to pre-erythrocytic and erythrocytic antigens.
- P. vivax pre-erythrocytic–stage proteins.
- P. vivax protein array fabrication.
- Serum screening using P. vivax protein arrays.
- Protein array data analysis.
- Bioinformatic analyses of novel P. vivax antigens.
- Results
- Discussion
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Guerra CA, Howes RE, Patil AP, Gething PW, Van Boeckel TP, Temperley WH, Kabaria CW, Tatem AJ, Manh BH, Elyazar IRF, Baird JK, Snow RW, Hay SI, 2010. The international limits and population at risk of Plasmodium vivax transmission in 2009. PLoS Negl Trop Dis 4: e774.
-
2.
Price RN, Douglas NM, Anstey NM, 2009. New developments in Plasmodium vivax malaria: severe disease and the rise of chloroquine resistance. Curr Opin Infect Dis 22: 430–435.
-
3.
Feachem RGA, Phillips AA, Hwang J, Cotter C, Wielgosz B, Greenwood BM, Sabot O, Rodriguez MH, Abeyasinghe RR, Ghebreyesus TA, Snow RW, 2010. Shrinking the malaria map: progress and prospects. Lancet 376: 1566–1578.
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Mason SJ, Miller LH, Shiroishi T, Dvorak JA, McGinniss MH, 1977. The Duffy blood group determinants: their role in the susceptibility of human and animal erythrocytes to Plasmodium knowlesi malaria. Br J Haematol 36: 327–335.
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Mendes C, Dias F, Figueiredo J, Mora VG, Cano J, de Sousa B, do Rosario VE, Benito A, Berzosa P, Arez AP, 2011. Duffy negative antigen is no longer a barrier to Plasmodium vivax: molecular evidences from the African west coast (Angola and Equatorial Guinea). PLoS Negl Trop Dis 5: e1192.
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Wurtz N, Mint Lekweiry K, Bogreau H, Pradines B, Rogier C, Ould Mohamed Salem Boukhary A, Hafid JE, Ould Ahmedou Salem MS, Trape J-F, Basco L, Briolant S, 2011. Vivax malaria in Mauritania includes infection of a Duffy-negative individual. Malar J 10: 336.
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Plasmodium vivax Pre-Erythrocytic–Stage Antigen Discovery: Exploiting Naturally Acquired Humoral Responses
Douglas M. Molina
Douglas M. Molina
Antigen Discovery Inc., Irvine, California; Seattle Biomedical Research Institute, Seattle, Washington; Centro Internacional de Vacunas, Instituto de Inmunología, Universidad del Valle, Cali, Colombia; Departments of Infectious Disease and Epidemiology, School of Medicine, University of California, Irvine, California
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Olivia C. Finney
Olivia C. Finney
Antigen Discovery Inc., Irvine, California; Seattle Biomedical Research Institute, Seattle, Washington; Centro Internacional de Vacunas, Instituto de Inmunología, Universidad del Valle, Cali, Colombia; Departments of Infectious Disease and Epidemiology, School of Medicine, University of California, Irvine, California
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Myriam Arevalo-Herrera
Myriam Arevalo-Herrera
Antigen Discovery Inc., Irvine, California; Seattle Biomedical Research Institute, Seattle, Washington; Centro Internacional de Vacunas, Instituto de Inmunología, Universidad del Valle, Cali, Colombia; Departments of Infectious Disease and Epidemiology, School of Medicine, University of California, Irvine, California
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Socrates Herrera
Socrates Herrera
Antigen Discovery Inc., Irvine, California; Seattle Biomedical Research Institute, Seattle, Washington; Centro Internacional de Vacunas, Instituto de Inmunología, Universidad del Valle, Cali, Colombia; Departments of Infectious Disease and Epidemiology, School of Medicine, University of California, Irvine, California
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Philip L. Felgner
Philip L. Felgner
Antigen Discovery Inc., Irvine, California; Seattle Biomedical Research Institute, Seattle, Washington; Centro Internacional de Vacunas, Instituto de Inmunología, Universidad del Valle, Cali, Colombia; Departments of Infectious Disease and Epidemiology, School of Medicine, University of California, Irvine, California
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Malcolm J. Gardner
Malcolm J. Gardner
Antigen Discovery Inc., Irvine, California; Seattle Biomedical Research Institute, Seattle, Washington; Centro Internacional de Vacunas, Instituto de Inmunología, Universidad del Valle, Cali, Colombia; Departments of Infectious Disease and Epidemiology, School of Medicine, University of California, Irvine, California
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Xiaowu Liang
Xiaowu Liang
Antigen Discovery Inc., Irvine, California; Seattle Biomedical Research Institute, Seattle, Washington; Centro Internacional de Vacunas, Instituto de Inmunología, Universidad del Valle, Cali, Colombia; Departments of Infectious Disease and Epidemiology, School of Medicine, University of California, Irvine, California
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Ruobing Wang
Ruobing Wang
Antigen Discovery Inc., Irvine, California; Seattle Biomedical Research Institute, Seattle, Washington; Centro Internacional de Vacunas, Instituto de Inmunología, Universidad del Valle, Cali, Colombia; Departments of Infectious Disease and Epidemiology, School of Medicine, University of California, Irvine, California
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The development of pre-erythrocytic Plasmodium vivax vaccines is hindered by the lack of in vitro culture systems or experimental rodent models. To help bypass these roadblocks, we exploited the fact that naturally exposed Fy− individuals who lack the Duffy blood antigen (Fy) receptor are less likely to develop blood-stage infections; therefore, they preferentially develop immune responses to pre-erythrocytic–stage parasites, whereas Fy+ individuals experience both liver- and blood-stage infections and develop immune responses to both pre-erythrocytic and erythrocytic parasites. We screened 60 endemic sera from P. vivax-exposed Fy+ or Fy− donors against a protein microarray containing 91 P. vivax proteins with P. falciparum orthologs that were up-regulated in sporozoites. Antibodies against 10 P. vivax antigens were identified in sera from P. vivax-exposed individuals but not unexposed controls. This technology has promising implications in the discovery of potential vaccine candidates against P. vivax malaria.
Author Notes
Financial support: This work was supported by National Institutes of Health/National Institute of Allergy and Infectious Disease Grant R01 AI05759206, National Institutes of Health/National Institute of Allergy and Infectious Disease Small Business Innovation Research Grant AI075692, and National Institutes of Health/National Heart, Lung, and Blood Institute Grant R01 RHLO86488-04. This work was also supported by the Columbian Administrative Department of Science, Technology and Innovaton, known as Colciencias, contract 527-2009, code 2304-493-26209.
Authors' addresses: Douglas M. Molina and Xiaowu Liang, Antigen Discovery Inc., Irvine, CA, E-mails: dmolina@antigendiscovery.com and xliang@antigendiscovery.com. Olivia C. Finney, Malcolm J. Gardner, and Ruobing Wang, Seattle Biomedical Research Institute, Seattle, WA, E-mails: Olivia.finney@seattlebiomed.org, Malcolm.gardner@seattlebiomed.org, and ruobing.wang@seattlebiomed.org. Myriam Arevalo-Herrera and Socrates Herrera, Centro Internacional de Vacunas, Instituto de Inmunología, Universidad del Valle, Cali, Colombia, E-mails: marevalo@inmuno.org and sherrera@inmuno.org. Phillip L. Felgner Departments of Infectious Disease and Epidemiology, School of Medicine, University of California, Irvine, CA, E-mail: pfelgner@uci.edu.
- Introduction
- Materials and Methods
- Recruitment of P. vivax-exposed and -naïve donors.
- Screening of sera by enzyme-linked immunosorbent assay and immunofluorescent assays to assess reactivity to pre-erythrocytic and erythrocytic antigens.
- P. vivax pre-erythrocytic–stage proteins.
- P. vivax protein array fabrication.
- Serum screening using P. vivax protein arrays.
- Protein array data analysis.
- Bioinformatic analyses of novel P. vivax antigens.
- Results
- Discussion
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Guerra CA, Howes RE, Patil AP, Gething PW, Van Boeckel TP, Temperley WH, Kabaria CW, Tatem AJ, Manh BH, Elyazar IRF, Baird JK, Snow RW, Hay SI, 2010. The international limits and population at risk of Plasmodium vivax transmission in 2009. PLoS Negl Trop Dis 4: e774.
-
2.
Price RN, Douglas NM, Anstey NM, 2009. New developments in Plasmodium vivax malaria: severe disease and the rise of chloroquine resistance. Curr Opin Infect Dis 22: 430–435.
-
3.
Feachem RGA, Phillips AA, Hwang J, Cotter C, Wielgosz B, Greenwood BM, Sabot O, Rodriguez MH, Abeyasinghe RR, Ghebreyesus TA, Snow RW, 2010. Shrinking the malaria map: progress and prospects. Lancet 376: 1566–1578.
-
4.
Horuk R, Chitnis CE, Darbonne WC, Colby TJ, Rybicki A, Hadley TJ, Miller LH, 1993. A receptor for the malarial parasite Plasmodium vivax: the erythrocyte chemokine receptor. Science 261: 1182–1184.
-
5.
Gelpi AP, King MC, 1976. Duffy blood group and malaria. Science 191: 1284.
-
6.
Miller LH, Mason SJ, Dvorak JA, McGinniss MH, Rothman IK, 1975. Erythrocyte receptors for Plasmodium knowlesi malaria: Duffy blood group determinants. Science 189: 561–563.
-
7.
Mason SJ, Miller LH, Shiroishi T, Dvorak JA, McGinniss MH, 1977. The Duffy blood group determinants: their role in the susceptibility of human and animal erythrocytes to Plasmodium knowlesi malaria. Br J Haematol 36: 327–335.
-
8.
Miller LH, Mason SJ, Clyde DF, McGinniss MH, 1976. The resistance factor to Plasmodium vivax in blacks. The Duffy-blood-group genotype, FyFy. N Engl J Med 295: 302–304.
-
9.
Adams JH, Sim BK, Dolan SA, Fang X, Kaslow DC, Miller LH, 1992. A family of erythrocyte binding proteins of malaria parasites. Proc Natl Acad Sci USA 89: 7085–7089.
-
10.
Young MD, Eyles DE, Burgess RW, Jeffrey GM, 1955. Experimental testing of the immunity of Negroes to Plasmodium vivax. J Parasitol 41: 315.
-
11.
Menard D, Barnadas C, Bouchier C, Henry-Halldin C, Gray LR, Ratsimbasoa A, Thonier V, Carod J-F, Domarle O, Colin Y, Bertrand O, Picot J, King CL, Grimberg BT, Mercereau-Puijalon O, Zimmerman PA, 2010. Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people. Proc Natl Acad Sci USA 107: 5967–5971.
-
12.
Mendes C, Dias F, Figueiredo J, Mora VG, Cano J, de Sousa B, do Rosario VE, Benito A, Berzosa P, Arez AP, 2011. Duffy negative antigen is no longer a barrier to Plasmodium vivax: molecular evidences from the African west coast (Angola and Equatorial Guinea). PLoS Negl Trop Dis 5: e1192.
-
13.
Wurtz N, Mint Lekweiry K, Bogreau H, Pradines B, Rogier C, Ould Mohamed Salem Boukhary A, Hafid JE, Ould Ahmedou Salem MS, Trape J-F, Basco L, Briolant S, 2011. Vivax malaria in Mauritania includes infection of a Duffy-negative individual. Malar J 10: 336.
-
14.
Wang R, Arevalo-Herrera M, Gardner MJ, Bonelo A, Carlton JM, Gomez A, Vera O, Soto L, Vergara J, Bidwell SL, Domingo A, Fraser CM, Herrera S, 2005. Immune responses to Plasmodium vivax pre-erythrocytic stage antigens in naturally exposed Duffy-negative humans: a potential model for identification of liver-stage antigens. Eur J Immunol 35: 1859–1868.
-
15.
Herrera S, Gomez A, Vera O, Vergara J, Valderrama-Aguirre A, Maestre A, Mendez F, Wang R, Chitnis CE, Yazdani SS, Arevalo-Herrera M, 2005. Antibody response to Plasmodium vivax antigens in Fy-negative individuals from the Columbian Pacific Coast. Am J Trop Med Hyg 73 (Suppl 5): 44–49.
-
16.
Maestre A, Muskus C, Duque V, Agudelo O, Liu P, Takagi A, Ntumngia FB, Adams JH, Sim KL, Hoffman SL, Corradin G, Velez ID, Wang R, 2010. Acquired antibody responses against Plasmodium vivax infection vary with host genotype for Duffy antigen receptor for chemokines (DARC). PLoS One 5: e11437.
-
17.
Urban BC, Roberts DJ, 2003. Inhibition of T cell function during malaria: implications for immunology and vaccinology. J Exp Med 197: 137–141.
-
18.
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