Lack of Avidity Maturation of Merozoite Antigen-Specific Antibodies with Increasing Exposure to Plasmodium falciparum amongst Children and Adults Exposed to Endemic Malaria in Kenya

Frances Ibison,Domtila Kimani,Kevin Marsh,Philip Bejon,Daniel M Muema,Ally Olotu,Jedida Mwacharo,Francis M Ndungu,Eric Ohuma,David J Sullivan

doi:10.1371/journal.pone.0052939

Abstract

BackgroundAlthough antibodies are critical for immunity to malaria, their functional attributes that determine protection remain unclear. We tested for associations between antibody avidities to Plasmodium falciparum (Pf) antigens and age, asymptomatic parasitaemia, malaria exposure index (a distance weighted local malaria prevalence) and immunity to febrile malaria during 10-months of prospective follow up.MethodsCross-sectional antibody levels and avidities to Apical Membrane Antigen 1 (AMA1), Merozoite Surface Protein 142 (MSP1) and Merozoite Surface Protein 3 (MSP3) were measured by Enzyme Linked Immunosorbent Assay in 275 children, who had experienced at least one episode of clinical malaria by the time of this study, as determined by active weekly surveillance.ResultsAntibody levels to AMA1, MSP1 and MSP3 increased with age. Anti-AMA1 and MSP1 antibody avidities were (respectively) positively and negatively associated with age, while anti-MSP3 antibody avidities did not change. Antibody levels to all three antigens were elevated in the presence of asymptomatic parasitaemia, but their associated avidities were not. Unlike antibody levels, antibody avidities to the three-merozoite antigens did not increase with exposure to Pf malaria. There were no consistent prospective associations between antibody avidities and malaria episodes.ConclusionWe found no evidence that antibody avidities to Pf-merozoite antigens are associated with either exposure or immunity to malaria.

Highlights

The anti-parasitic and therapeutic effects of passively transferred malaria immune IgG, from immune adults to children or adults with malaria, provided strong evidence that antibodies are critical mediators of naturally acquired immunity to malaria [1,2,3]
Previous studies have implicated cytophilic IgG1 and IgG3 antibodies in parasite killing mechanisms like opsonisation, phagocytosis and antibody dependent cellular inhibition (ADCI) that require cooperation with monocytes and macrophages via FccRI and FccRII [8,9]
Antibody avidity is an important correlate for immune memory and protective immunity in other infections [11,12] and vaccine trials [13,14], but has only rarely been studied in malaria

Summary

Introduction

The anti-parasitic and therapeutic effects of passively transferred malaria immune IgG, from immune adults to children or adults with malaria, provided strong evidence that antibodies are critical mediators of naturally acquired immunity to malaria [1,2,3]. Subsequent sero-epidemiological studies to identify antibody specificities and mechanisms of immunity have produced conflicting results and have failed to reveal measurable correlates of protection [4,5]. Antibody avidity is an important correlate for immune memory and protective immunity in other infections [11,12] and vaccine trials [13,14], but has only rarely been studied in malaria. Antibodies are critical for immunity to malaria, their functional attributes that determine protection remain unclear. We tested for associations between antibody avidities to Plasmodium falciparum (Pf) antigens and age, asymptomatic parasitaemia, malaria exposure index (a distance weighted local malaria prevalence) and immunity to febrile malaria during 10-months of prospective follow up

Methods

Results

Conclusion