WORLDWIDE GENETIC POLYMORPHISM OF CIRCUMSPOROZOITE PROTEIN IN PLASMODIUM VIVAX SEQUENCES: A SYSTEMATIC REVIEW

Abstract

The Circumsporozoite Protein of Plasmodium vivax (PvCSP) is an immunodominant antigen expressed on the surface of the sporozoite. PvCSP consists of a central repetitive region (CRR), capable of stimulating both T and B lymphocytes. The CRR is flanked by two non-repetitive regions, N-terminal (RI) and C-terminal (RII), which play important roles in parasite invasion and motility, both in the vector and the human host. Due to its highly immunogenic regions, PvCSP is considered one of the main candidates for a malaria vaccine. However, the genetic diversity of PvCSP poses a challenge for immunobiological research. This study aimed to evaluate the presence of polymorphisms in the VK210, VK247, and P. vivax-like variants of PvCSP worldwide through a systematic review. Genetic diversity of PvCSP from different regions of the world was investigated using nucleotide sequences retrieved from GenBank and analyzed for polymorphisms in RI, RII, and CRR using Mega4 software. Out of 709 sequences analyzed, VK210 (n = 591) was the most prevalent worldwide, followed by VK247 (n = 116) and P. vivax-like (n = 2). Polymorphisms in RI were observed only for VK210, in isolates from Myanmar (n = 4) and India (n = 12). Isolates from Brazil (n = 4), Myanmar (n = 29), Vanuatu (n = 10), Cambodia (n = 21), Colombia (n = 2), Papua New Guinea (n = 11), Sudan (n = 30), and India (n = 5) showed polymorphisms resulting in the insertion of an Alanine after RI, which was not observed in Iran (n = 45), South Korea (n = 2), Mexico (n = 11), Nicaragua (n = 4), Pakistan (n = 32), and Greece (n = 1). In the CRR, VK210 presented more polymorphisms (n = 217) than VK247 (n = 36), and no polymorphisms were found for P. vivax-like. Region II of PvCSP also showed genetic variations in the global population, generating different patterns of insertion and deletion of the ANKKAEDA octapeptide for VK210 isolates from Myanmar (n = 16), Cambodia (n = 4), South Korea (n = 2), Mexico (n = 7), Pakistan (n = 32), Greece (n = 1), but not observed in Brazil, Colombia, Nicaragua, Papua New Guinea, Vanuatu, and Sudan. For VK247, isolates from Cambodia were the only ones that did not show insertion of the ANKKAGDA octapeptide. No variation was observed for P. vivax-like. These data reflect the complexity in developing an anti-sporozoite vaccine against P. vivax, as the analyzed sequences present different polymorphisms causing synonymous and non-synonymous nucleotide variations, especially in the CRR. Keywords: Epidemiology, Vivax Malaria, Genetic polymorphism, Vaccine. Conflicts of interest: There was no conflicts of interest. Ethics and financing: Declarations of interest: None.