The malaria candidate vaccine liver stage antigen-3 is highly conserved in Plasmodium falciparum isolates from diverse geographical areas.
BACKGROUND
A high level of genetic stability has been formerly identified in segments of the gene coding for the liver stage antigen-3 (LSA-3), a subunit vaccine candidate against Plasmodium falciparum. The exploration of lsa-3 polymorphisms was extended to the whole sequence of this large antigen in 20 clinical isolates from four geographical areas; Senegal, Comoro islands, Brazil and Thailand.


METHODS
The whole 4680 bp genomic sequence of lsa-3 was amplified by polymerase chain reaction and sequenced. The clinical isolate sequences were aligned on the sequence of the laboratory reference P. falciparum strain 3D7.


RESULTS
The non-repeated sequence of lsa-3 was very well conserved with only a few allelic variations scattered along the sequence. Interestingly, a formerly identified immunodominant region, employed for the majority of pre-clinical vaccine development, was totally conserved at the genetic level. The most significant variations observed were in the number and organization of tetrapeptide repeated units, but not in their composition, resulting in different lengths of these repeated regions. The shorter repeated regions were from Brazilian origin. A correlation between the geographical distribution of the parasites with single nucleotide polymorphisms was not detected.


CONCLUSIONS
The lack of correlation between allelic polymorphisms with a specific transmission pressure suggests that LSA-3 is a structurally constrained molecule. The unusual characteristics of the lsa-3 gene make the molecule an interesting candidate for a subunit vaccine against malaria.
Prieur
Eric
E
Biochemical Parasitology Unit, Institut Pasteur, Paris, France. prieur@pasteur.fr
Druilhe
Pierre
P
D000818:Animals; D000953:Antigens, Protozoan; D001938:Brazil; D017507:Comoros; D019075:Electrophoresis, Capillary; D018503:Genome, Protozoan; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012675:Senegal; D017421:Sequence Analysis; D013785:Thailand
D000953:Antigens, Protozoan; D017780:Malaria Vaccines; C067302:liver stage-specific antigen, Plasmodium