title: Genetic diversity of the malaria vaccine candidate Plasmodium falciparum merozoite surface protein-3 in a hypoendemic transmission environment.
abstract: The N-terminal domain of Plasmodium falciparum merozoite surface protein-3 (PfMSP3) has been excluded from malaria vaccine development largely because of genetic diversity concerns. However, no study to date has followed N-terminal diversity over time. This study describes PfMSP3 variation in a hypoendemic longitudinal cohort in the Peruvian Amazon over the 2003-2006 transmission seasons. Polymerase chain reaction was used to amplify the N-terminal domain in 630 distinct P. falciparum infections, which were allele-typed by size and also screened for sequence variation using a new high-throughput technique, denaturing high performance liquid chromatography. PfMSP3 allele frequencies fluctuated significantly over the 4-year period, but sequence variation was very limited, with only 10 mutations being identified of 630 infections screened. The sequence of the PfMSP3 N-terminal domain is relatively stable over time in this setting, and further studies of its status as a vaccine candidate are therefore warranted.
authors.affiliation: Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294-2170, USA. sjjordan@uab.edu
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Jordan
authors.forename: OraLee H
authors.initials: OH
authors.lastname: Branch
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Castro
authors.forename: Jean Carlos
authors.initials: JC
authors.lastname: Castro
authors.forename: Robert A
authors.initials: RA
authors.lastname: Oster
authors.forename: Julian C
authors.initials: JC
authors.lastname: Rayner
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics* / Q000276:immunology*; D002851:Chromatography, High Pressure Liquid; D019353:Endemic Diseases / Q000517:prevention & control; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control* / Q000635:transmission; D008297:Male; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000235:genetics* / Q000276:immunology*; D055815:Young Adult
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C089133:merozoite surface protein 3, Plasmodium