Background:
Plasmodium falciparum cell-traversal protein for ookinetes and sporozoites (PfCelTOS) has been reported as one of the most attractive malaria vaccine candidate antigens. To design a broadly protective falciparum vaccine based on PfCelTOS, it is essential to have adequate information on genetic diversity of pfceltos gene and also the naturally acquired antibodies to this antigens.Objectives: The main objectives of the present study were to analyze the genetic diversity of celtos gene in P. falciparum isolates and also to evaluate naturally acquired antibodies to the most prevalent variant form of PfCelTOS among the patients infected with P. falciparum from unstable malaria transmission settings of Iran.Materials and Methods:
Genetic diversity of pfceltos gene were analyzed in Iranian P. falciparum isolates (n = 93) and compared with the corresponding sequences from worldwide clinical P. falciparum isolates retrieved from Plasmodb database (n = 159). Furthermore, the most prevalent variant form of PfCelTOS in Iranian P. falciparum isolates was expressed in Escherichia coli BL21 (DE3)-pET23a and used as antigen in enzyme-linked immunosorbent assay (ELISA). The profile of immunoglobulin G (IgG) isotype and the avidity of anti-PfCelTOS antibodies were assessed to evaluate the naturally acquired antibodies to PfCelTOS in Iranian P. alciparum infected patients (n = 204).Results: The nucleotide sequence analysis of pfceltos gene in comparison with 3D7 sequence showed the occurrence of 39 amino acid substitutions at 23 positions in global isolates, resulting in 66 different haplotypes. In addition, serological analysis showed that 16.2% (33/204) of the studied individuals had positive IgG responses to PfCelTOS with a marked isotype switching to cytophilic (IgG1 and IgG3) antibodies.Conclusion: The present analysis demonstrates that there is a limited antigenic diversity in Iranian and global PfCelTOS and this finding may be associated with the critical function of this antigen in cell traversal of the parasite in sporozoite and ookinete. The present data also suggests the presence of mature and protective IgG1 and IgG3 antibodies with high to intermediate avidity against PfCelTOS antigen (> 70%) that could help to understand the interactions between the host and P. falciparum parasite in developing and testing a CelTOS-based vaccine.