Immunogenicity of glycosylphosphatidylinositol-anchored micronemal antigen in natural Plasmodium vivax exposure

Abstract

Background Plasmodium vivax is the most geographically widespread malaria species and codominates with Plasmodium falciparum, the deadliest form of the malaria parasite. For the last few years, the number of vivax malaria cases has increased, but vivax malaria is still considered a neglected disease. During the blood stages of their life cycle, P. vivax parasites export several hundred proteins into host red blood cells. Some of these exported proteins have been discovered and studied for use as a blood-stage malaria vaccine. The P. vivax glycosylphosphatidylinositol (GPI)-anchored micronemal antigen (PvGAMA) was identified in previous study, which plays an important role in parasite invasion. To support the hypothesis that PvGAMA can induce an immune response in natural exposure, the antibody responses and cellular immunity against this antigen was demonstrated during and post-infection.MethodsThe recombinant protein PvGAMA was expressed and purified by wheat germ cell-free (WGCF) system. The analysis of humoral and cellular immune responses to the PvGAMA antigen during infection and post-infection with the P. vivax parasite were done by enzyme-linked immunosorbent assay (ELISA) techniques.ResultsDuring P. vivax infection, 95% of patients showed significant antibody responses to PvGAMA antigen. The cytophilic IgG1 and IgG3 isotypes were the major isotypes produced in response to PvGAMA. A cross-sectional study of anti-PvGAMA responses during and post-infection with P. vivax found that the majority of individuals, approximately 54% of patients, were shown to maintain a positive anti-PvGAMA titre at 3 months post-infection, and some patients had the ability to maintain an antibody response for up to 12 months post-infection. Moreover, PvGAMA had the ability to stimulate a cellular immune response that was characterized by the production of the cytokines IL-2, IFN-γ and IL-10. The levels of the cytokines IFN-γ and IL-10 were significantly increased in PvGAMA-stimulated lymphocyte cultures.ConclusionsTaken together, PvGAMA had potential to induce an immune response both humoral and cellular immunity in naturally acquired P. vivax infection individuals during infection and post-infection. Therefore, PvGAMA could be as a vaccine candidate to stimulate immune response against P. vivax infection.

UsingPlasmodium knowlesias a model for screeningPlasmodium vivaxblood-stage malaria vaccine targets reveals new candidates

“…We localised PkARP to the apical region of the merozoite, suggesting a possible location in the rhoptries like the PfARP homologue in P. falciparum (60), but in contrast to previous studies suggesting a merozoite surface location in P. vivax and P. knowlesi (52,61); again, experimental differences in the stage of parasites used might explain the different observations. PkGAMA also localised to apical organelles, replicating previous observations of a micronemal location in P. vivax (29) and P. falciparum (62,63). We were unable to inhibit P. knowlesi growth using anti-PvARP antibodies, contradicting what has been shown in P. knowlesi (64) and P. falciparum (60).…”

IgG subclass responses to excreted-secreted antigens of Plasmodium falciparum in a low-transmission malaria area of the Peruvian Amazon

“…Cytophilic subclasses of IgG (IgG1 and IgG3) have been considered the most important antibodies in the development of immunity to malaria, as these subclasses are capable of mediating the activation of leukocytes via their binding to FcγRI and FcγRIII. Together, the predominance of these subclasses is associated with lower risks of malaria-related complications in malaria-endemic areas [ 12 – 18 ].…”

The in Vitro Antigenicity of Plasmodium vivax Rhoptry Neck Protein 2 (PvRON2) B- and T-Epitopes Selected by HLA-DRB1 Binding Profile

“…Antibodies against P. vivax blood-stage proteins are important elements for blocking RBC invasion (Wipasa et al, 2002 ); such antibodies thus play an important role in identifying and validating P. vivax vaccine candidates (Soares et al, 1999 ; Lima-Junior et al, 2008 ; Storti-Melo et al, 2012 ; Changrob et al, 2017 ; Rodrigues-Da-Silva et al, 2017 ). We confirmed the presence of naturally-acquired humoral responses against four Pv RON2 B-epitopes which were recognized by IgG antibodies and subclasses.…”