Genetic sequence characterization and naturally acquired immune response to Plasmodium vivax Rhoptry Neck Protein 2 (PvRON2)

Abstract

BackgroundThe genetic diversity of malaria antigens often results in allele variant-specific immunity, imposing a great challenge to vaccine development. Rhoptry Neck Protein 2 (PvRON2) is a blood-stage antigen that plays a key role during the erythrocyte invasion of Plasmodium vivax. This study investigates the genetic diversity of PvRON2 and the naturally acquired immune response to P. vivax isolates.ResultsHere, the genetic diversity of PvRON21828–2080 and the naturally acquired humoral immune response against PvRON21828–2080 in infected and non-infected individuals from a vivax malaria endemic area in Brazil was reported. The diversity analysis of PvRON21828–2080 revealed that the protein is conserved in isolates in Brazil and worldwide. A total of 18 (19%) patients had IgG antibodies to PvRON21828–2080. Additionally, the analysis of the antibody response in individuals who were not acutely infected with malaria, but had been infected with malaria in the past indicated that 32 patients (33%) exhibited an IgG immune response against PvRON2.ConclusionsPvRON2 was conserved among the studied isolates. The presence of naturally acquired antibodies to this protein in the absence of the disease suggests that PvRON2 induces a long-term antibody response. These results indicate that PvRON2 is a potential malaria vaccine candidate.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2543-7) contains supplementary material, which is available to authorized users.

RON2, a novel gene in Babesia bigemina, contains conserved, immunodominant B-cell epitopes that induce antibodies that block merozoite invasion

“…(2018), demonstrate that conserved B-cell epitopes of RON2 are implicated in humoral immune responses in bovine babesiosis under natural conditions. Since the cattle sera analyzed were obtained from nineteen farms in four different states in Mexico, where bovine babesiosis antigens have been reported to be highly variable (Borgonio et al ., 2008; Genis et al ., 2008), our findings support the hypothesis that RON2 is highly immunogenic and contains conserved B-cell epitopes, as it was previously described in P. vivax (Bittencourt et al ., 2018; López et al ., 2018). However, broader analyses including sera from other endemic countries are needed to confirm this hypothesis.…”

“…This complex is discharged towards the RBC, and RON2 is integrated into the RBC membrane where it acts as an AMA-1 ligand on the parasite surface (Silvie et al ., 2004; Shen and Sibley, 2012). Blocking this interaction halts merozoite invasion, suggesting that RON2 may be a target for vaccine development (Srinivasan et al ., 2013, 2014; Zhang et al ., 2015; Bittencourt et al ., 2018; Salgado-Mejias et al ., 2019). Although RON2 has been described in Babesia divergens, B. microti and B. bovis (Ord et al ., 2016; Hidalgo-Ruiz et al ., 2018), to date, there is no evidence of RON2 in other species of Babesia , such as B. bigemina, where the presence of AMA-1 has been reported (Torina et al ., 2010).…”

Plasmodium vivax AMA1: Implications of distinct haplotypes for immune response

“…IgG reactive indexes greater than one were considered to be positive. Bias produced by a possible reactivity of the GST tag was evaluated as described by Bittencourt et al, 2018 [41].…”

Rosettes integrity protects Plasmodium vivax of being phagocytized

“…PvAMA-1 and PvMSP-1 19 recombinant proteins were expressed and purified as previously described 36,37 . ELISAs were conducted as previously described 38 . The results for IgG subclasses were expressed as reactivity indices (RIs), which were calculated by dividing the mean optical density (OD) values of tested samples by the mean OD values plus three standard deviations of 20 non-exposed individuals living in nonendemic areas of malaria.…”