Analysis of genetic diversity in a novel vaccine candidate, the glutamic acid-rich protein of Plasmodium Falciparum (PfGARP)

Abstract

Malaria vaccine development confronts high genetic polymorphism in some antigenic components of the vaccine candidates, which could potentially limit the vaccine efficacy. An antigen of Plasmodium falciparum, designated glutamic acid-rich protein (PfGARP), has recently been considered as a strong vaccine target against asexual-blood-stages parasite. It has been shown that naturally acquired anti-PfGARP antibodies elicited clinical protection against severe malaria among people living in hyperendemic areas. Furthermore, PfGARP has been involved in binding to human erythrocyte band 3, which induces erythrocyte aggregation and might bring about severe malaria. However, the extent of genetic variation in the pfgarp locus among field isolates remains unknown. Herein, the genetic diversity in the PfGARP encoding gene was evaluated using samples collected during 2009 - 2014 from different malaria-endemic areas in Thailand (Chanthaburi (n = 20), Tak (n = 20), Ubon Ratchathani (n = 20), and Yala (n = 20) Provinces) by direct sequencing. The analyzed data on 80 sequences revealed high conservation in pfgarp among the parasite populations. The gene contains two exons, exon I and exon II where the latter consists of 8 SNPs and 8 repeats. Twenty-six haplotypes distribute among the populations. Selective pressure measured by Tajima’s D was 0.397, not statistically significant (p value > 0.10), suggesting no deviation from selective neutrality at this locus among the parasite populations in Thailand. The lack of high genetic diversity in this gene appears to be a strong component for malaria vaccine.