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

Najara C Bittencourt,Helder I Nakaya,Joao C K Dos-Santos,Stefanie C P Lopes,João Luiz Silva-Filho,Letusa Albrecht,Marcelo U Ferreira,Tamirys S Pimenta,Catarina Bourgard,Fabio T M Costa,Ricardo L D Machado,Marcus V G Lacerda,Ana Maria Revorêdo Da Silva Ventura,Juliana A Leite,Gustavo C Cassiano,Ana Beatriz I E Silva

doi:10.1186/s12936-018-2543-7

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.

Highlights

The genetic diversity of malaria antigens often results in allele variant-specific immunity, imposing a great challenge to vaccine development
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

Summary

Introduction

The 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. Bittencourt et al Malar J (2018) 17:401 membrane and adopts a surface-exposed loop that binds to a hydrophobic groove in AMA1, which is secreted by micronemes at the parasite surface [1, 7, 8]. This interaction triggers the junction formation and the invasion process. In the same microenvironment of erythrocyte invasion, anti-parasite acquired immunity occurs largely through the recognition of blood stage antigens expressed by the merozoite. RON2 is present in various Plasmodium species and is likely exposed to the host immune system during erythrocyte invasion, making this protein a potential target for antibody-mediated protective immunity and vaccine development

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Conclusion