Plasmodium falciparum Antigens on the Surface of the Gametocyte-Infected Erythrocyte

Mauricio Martins Rodrigues,Maha Saeed,Colin J Sutherland,Christopher J Drakeley,Neal Alexander,Geoffrey A T Targett,Will Roeffen

doi:10.1371/journal.pone.0002280

Abstract

BackgroundThe asexual blood stages of the human malaria parasite Plasmodium falciparum produce highly immunogenic polymorphic antigens that are expressed on the surface of the host cell. In contrast, few studies have examined the surface of the gametocyte-infected erythrocyte.Methodology/Principal FindingsWe used flow cytometry to detect antibodies recognising the surface of live cultured erythrocytes infected with gametocytes of P. falciparum strain 3D7 in the plasma of 200 Gambian children. The majority of children had been identified as carrying gametocytes after treatment for malaria, and each donated blood for mosquito-feeding experiments. None of the plasma recognised the surface of erythrocytes infected with developmental stages of gametocytes (I–IV), but 66 of 194 (34.0%) plasma contained IgG that recognised the surface of erythrocytes infected with mature (stage V) gametocytes. Thirty-four (17.0%) of 200 plasma tested recognised erythrocytes infected with trophozoites and schizonts, but there was no association with recognition of the surface of gametocyte-infected erythrocytes (odds ratio 1.08, 95% C.I. 0.434–2.57; P = 0.851). Plasma antibodies with the ability to recognise gametocyte surface antigens (GSA) were associated with the presence of antibodies that recognise the gamete antigen Pfs 230, but not Pfs48/45. Antibodies recognising GSA were associated with donors having lower gametocyte densities 4 weeks after antimalarial treatment.Conclusions/SignificanceWe provide evidence that GSA are distinct from antigens detected on the surface of asexual 3D7 parasites. Our findings suggest a novel strategy for the development of transmission-blocking vaccines.

Highlights

Available evidence suggests that there are specific immune responses to different stages of the malaria parasite life cycle
Purity of synchronous gametocyte cultures Immunofluorescence experiments were performed to verify that asexual parasites had been eliminated from the starting gametocyte culture at day 8, as stage I gametocytes are difficult to discriminate from early trophozoites of the asexual lineage [39]
In this study of malaria patients identified as gametocyte carriers, we have demonstrated that erythrocytes infected with mature gametocytes of P. falciparum carry surface antigens that are recognised by naturally-elicited antibody responses

Summary

Introduction

Available evidence suggests that there are specific immune responses to different stages of the malaria parasite life cycle. Blood-stage immunity involves the acquisition of a repertoire of antibodies (IgG) directed against parasiteencoded variant surface antigens (VSA) on the surface of the infected erythrocyte [2,3]. Transmissible sexual stages of the malaria parasite, gametocytes, frequently die in the host without being passed on to a mosquito, and in doing so release intracellular antigens into the host circulation. Among these antigens are a number that elicit humoral responses which mediate transmission blocking immunity. This occurs when human antibodies, taken up by a mosquito in a potentially infective blood-meal containing male and female. Few studies have examined the surface of the gametocyte-infected erythrocyte

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Conclusion