The malaria candidate vaccine liver stage antigen-3 is highly conserved in Plasmodium falciparum isolates from diverse geographical areas

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.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.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.The human malaria parasite Plasmodium falciparum is responsible for 300-500 million clinical cases and 1-2 million deaths every year mainly among young African children [1]. The incidence of malaria among travellers from non-endemic areas is on the rise [2]. The emergence and spread of resistances against anti-malarial drugs makes the development of a vaccine an urgent need. Na？ve volunteers immunized with radiation-attenuated sporozoites [3], the form of the parasite injected in the host by a mosquito bite, but not killed parasites, were protected from a challenge with wild-type parasites. This observation suggests that the partial intra-hepatic development of the parasite was necessary to confer protection against the pre-erythrocytic (PE) stages of P. falciparum as it has been further verified with recently developed geneti