Genetic diversity of vaccine candidate antigens in Plasmodium falciparum isolates from the Amazon basin of Peru.
BACKGROUND
Several of the intended Plasmodium falciparum vaccine candidate antigens are highly polymorphic and could render a vaccine ineffective if their antigenic sites were not represented in the vaccine. In this study, characterization of genetic variability was performed in major B and T-cell epitopes within vaccine candidate antigens in isolates of P. falciparum from Peru.


METHODS
DNA sequencing analysis was completed on 139 isolates of P. falciparum collected from endemic areas of the Amazon basin in Loreto, Peru from years 1998 to 2006. Genetic diversity was determined in immunological important regions in circumsporozoite protein (CSP), merozoite surface protein-1 (MSP-1), apical membrane antigen-1 (AMA-1), liver stage antigen-1 (LSA-1) and thrombospondin-related anonymous protein (TRAP). Alleles identified by DNA sequencing were aligned with the vaccine strain 3D7 and DNA polymorphism analysis and FST study-year pairwise comparisons were done using the DnaSP software. Multilocus analysis (MLA) was performed and average of expected heterozygosity was calculated for each loci and haplotype over time.


RESULTS
Three different alleles for CSP, seven for MSP-1 Block 2, one for MSP-1 Block 17, three for AMA-1 and for LSA-1 each and one for TRAP were identified. There were 24 different haplotypes in 125 infections with complete locus typing for each gene.


CONCLUSIONS
Characterization of the genetic diversity in Plasmodium isolates from the Amazon Region of Peru showed that P. falciparum T and B cell epitopes in these antigens have polymorphisms more similar to India than to Africa. These findings are helpful in the formulation of a vaccine considering restricted repertoire populations.
Chenet
Stella M
SM
Parasitology Program, Naval Medical Research Center Detachment, Lima, Peru. stella.chenet@med.navy.mil
Branch
Oralee H
OH
Escalante
Ananias A
AA
Lucas
Carmen M
CM
Bacon
David J
DJ
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics*; D018985:Epitopes, B-Lymphocyte / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D010568:Peru; D010963:Plasmodium falciparum / Q000235:genetics*; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D000953:Antigens, Protozoan; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte