Heterogeneity in the acquisition of naturally acquired antibodies to cell-traversal protein for ookinetes and sporozoites (CelTOS) and thrombospondin-related adhesion protein (TRAP) of Plasmodium falciparum in naturally infected patients from unstable malaria areas in Iran

Currently, there is no subunit malaria vaccine capable of providing long-lasting protection, and a vaccine based on a single-antigen has shown moderate to unsatisfactory efficacies in clinical trials. As in malaria elimination and eradication strategies, the primary objective is reduction in disease and death due to P. falciparum, in the present investigation, for the first time, we attempted to determine and compare the naturally acquired immune responses to two well-recognized sporozoite antigens, cell-traversal protein for ookinetes and sporozoites (CelTOS) and thrombospondin-related adhesion protein (TRAP), in P. falciparum-infected individuals (n = 204) in low malaria transmission settings of Iran using ELISA. Besides, the profile of IgG isotype responses, the avidity of IgG, IgG1, and IgG3, and the association of anti-PfCelTOS and -PfTRAP antibodies with host age were evaluated. Positive antibody responses to PfCelTOS and PfTRAP antigens were detected in 16.2% and 31.9% of Iranian P. falciparum-infected individuals, respectively, indicating significantly lower immune response to PfCelTOS than PfTRAP (P <0.0001, McNemar's test). Also, among the positive samples for anti-PfCelTOS (n = 33) and -PfTRAP (n = 65) total IgG, the cytophilic IgG1 and IgG3 antibodies were predominant. A significant proportion of the examined positive responders had high- and intermediate-avidity for IgG (93.9%, 87.7%), IgG1 (96.3%, 87.7%), and IgG3 (76%, 78.7%) antibodies to both PfCelTOS and PfTRAP antigens, respectively, with no correlation with age (P >0.05; Spearman’s correlation test). In conclusion, the present data suggests the acquisition of heterogenic immune responses to both antigens in the same patients naturally infected with P. falciparum from settings of low malaria transmission intensity in Iran in which their role in protection to malaria needs further study.