The presence of circulating antibody secreting cells and long-lived memory B cell responses to reticulocyte binding protein 1a in Plasmodium vivax patients

Piyawan Kochayoo,Francis B Ntumngia,Patchanee Chootong,John H Adams,Kittikorn Wangriatisak,Pattarawan Sanguansuttikul,Pongsakorn Thawornpan

doi:10.1186/s12936-021-04015-3

Piyawan Kochayoo, Francis B Ntumngia + Show 5 more

Open Access

https://doi.org/10.1186/s12936-021-04015-3

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Abstract

BackgroundDevelopment of an effective vaccine against blood-stage malaria requires the induction of long-term immune responses. Plasmodium vivax Reticulocyte Binding Protein 1a (PvRBP1a) is a blood-stage parasite antigen which is associated with invasion of red blood cells and induces antibody responses. Thus, PvRBP1a is considered as a target for design of a blood-stage vaccine against vivax malaria.MethodsBoth cross-sectional and cohort studies were used to explore the development and persistence of long-lived antibody and memory B cell responses to PvRBP1a in individuals who lived in an area of low malaria endemicity. Antibody titers and frequency of memory B cells specific to PvRBP1a were measured during infection and following recovery for up to 12 months.ResultsIgG antibody responses against PvRBP1a were prevalent during acute vivax malaria, predominantly IgG1 subclass responses. High responders to PvRBP1a had persistent antibody responses for at least 12-month post-infection. Further analysis of high responder found a direct relation between antibody titers and frequency of activated and atypical memory B cells. Furthermore, circulating antibody secreting cells and memory B cells specific to PvRBP1a were generated during infection. The PvRBP1a-specific memory B cells were maintained for up to 3-year post-infection, indicating the ability of PvRBP1a to induce long-term humoral immunity.ConclusionThe study revealed an ability of PvRBP1a protein to induce the generation and maintenance of antibody and memory B cell responses. Therefore, PvRBP1a could be considered as a vaccine candidate against the blood-stage of P. vivax.

Highlights

Development of an effective vaccine against blood-stage malaria requires the induction of long-term immune responses
Infections by P. vivax produced anti‐Plasmodium vivax Reticulocyte Binding Protein 1a (PvRBP1a) responses To determine the seroprevalence of anti-PvRBP1a antibody responses in natural infection to the P. vivax parasite, a cross-sectional survey of antibody levels against this antigen was conducted in acutely infected patients
Significant decreases of circulating PvRBP1a-specific antibody secreting cells (ASCs) were observed. These findings suggest that PvRBP1a can induce the generation of Memory B cells (MBCs) and ASCs during P. vivax infection and that these cells are maintained in the absence of re-infection independent of the duration of antibody responses

Summary

Introduction

Development of an effective vaccine against blood-stage malaria requires the induction of long-term immune responses. Plasmodium vivax Reticulocyte Binding Protein 1a (PvRBP1a) is a blood-stage parasite antigen which is associated with invasion of red blood cells and induces antibody responses. One of the leading blood-stage vaccine candidates is P. vivax duffy binding protein (PvDBP), a parasite cell surface protein in the erythrocyte binding-like (EBL) invasion protein family [8, 9]. This protein binds to the duffy antigen receptor for chemokines (DARC), a receptor on the surface of the erythrocyte [10]. Finding new vaccine candidates with distinct target antigens is necessary

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