Antibodies to Plasmodium vivax reticulocyte binding protein 2b are associated with protection against P. vivax malaria in populations living in low malaria transmission regions of Brazil and Thailand.

Wen-Qiang He,Wang Nguitragool,Marcus V G Lacerda,Jakub Gruszczyk,Ivo Mueller,Wuelton Monteiro,Jetsumon Sattabongkot,Wai-Hong Tham,Michael T White,Andrea Kuehn,Stephan Karl,Camila T França

doi:10.1371/journal.pntd.0007596

Abstract

BackgroundThe Plasmodium vivax Reticulocyte Binding Protein (PvRBP) family is involved in red blood cell recognition and members of this family are potential targets for antibodies that may block P. vivax invasion. To date, the acquisition of immunity against PvRBPs in low malaria transmission settings and in a broad age group of exposed individuals has not been investigated.Methodology/Principal findingsTotal IgG antibody levels to six members of the PvRBP family (PvRBP1a, PvRBP1b, PvRBP2a, PvRBP2b, a non-binding fragment of PvRBP2c (PvRBP2cNB) and PvRBP2-P2) were measured in samples collected from individuals living in two regions of low P. vivax endemicity in Brazil and Thailand. In both settings, levels of total IgG to PvRBP1a, PvRBP2b, PvRBP2cNB, and PvRBP2P-2 increased significantly with age (rho = 0.17–0.49; P<0.001). IgG responses to PvRBP1a, PvRBP2b and PvRBP2cNB were significantly higher in infected individuals by using Wilcoxon’s signed-rank test (P<0.001). Of the six PvRBPs examined, only antibodies to PvRBP2b were associated with protection against clinical malaria in both settings.Conclusion/SignificanceOur results indicate that PvRBP2b warrants further preclinical development as a blood-stage vaccine candidate against P. vivax. Total IgG responses to PvRBPs were also shown to be promising immunological markers of exposure to P. vivax infection.

Highlights

Plasmodium vivax is the most widespread human malaria parasite species [1]
Using samples from longitudinal cohort studies from regions of low P. vivax endemicity in Brazil and Thailand, we showed that antibody responses to PvRBP1a, PvRBP2b, and PvRBP2cNB increased with age and were boosted during infection
Higher antibody levels to PvRBP2b were strongly associated with a lower risk of clinical episodes of P. vivax

Summary

Introduction

Plasmodium vivax is the most widespread human malaria parasite species [1]. 4% of estimated cases globally are caused by P. vivax, this proportion is 36% outside the African continent [2]. The majority of P. vivax infection occurs in the South-East Asia Region, which accounts for 58% of cases worldwide [2]. P. vivax accounts for more than 30% of total malaria cases in South-East Asia and 64% in the Americas. In some countries, such as Thailand and Brazil, P. vivax infection is responsible for 80% and 90% of malaria cases respectively [2]. As many countries progress towards the malaria elimination, P. vivax infection has emerged as one of the key challenges [3]. In low-transmission settings reduced exposure leads to all age groups being at risk of clinical P. vivax illness [9]. The acquisition of immunity against PvRBPs in low malaria transmission settings and in a broad age group of exposed individuals has not been investigated

Results

Discussion

Conclusion