Abstract
Understanding the functional characteristics of naturally acquired antibodies against P. falciparum merozoite antigens is crucial for determining the protective functions of antibodies. Affinity (measured as kd) of naturally acquired antibodies against two key targets of acquired immunity, EBA175 and PfRh2, was determined using Surface Plasmon Resonance (SPR) in a longitudinal survey in Nigeria. A majority of the participants, 79% and 67%, maintained stable antibody affinities to EBA175 and PfRh2, respectively, over time. In about 10% of the individuals, there was a reciprocal interaction with a reduction over time in antibody affinity for PfRh2 and an increase for EBA175. In general, PfRh2 elicited antibodies with higher affinity compared to EBA175. Individuals with higher exposure to malaria produced antibodies with higher affinity to both antigens. Younger individuals (5–15 years) produced comparable or higher affinity antibodies than adults (>15 years) against EBA175, but not for PfRh2. Correlation between total IgG (ELISA) and affinity varied between individuals, but PfRh2 elicited antibodies with a higher correlation in a majority of the participants. There was also a correlation between antibody inhibition of erythrocyte invasion by merozoites and PfRh2 affinity. This work gives new insights into the generation and maintenance of antibody affinity over time.
Highlights
Despite the enormity of global financial commitment to malaria control[1,2], malaria is still considered endemic in 91 countries with an estimated 212 million cases and 429,000 deaths in 20153
In this study we have investigated the changes in affinity over time of antibodies produced against two antigens that are targets of naturally-acquired immunity EBA17528 and Plasmodium falciparum Reticulocyte Homologue Protein 2 (PfRh2)[29]
We investigated changes in affinity of antibodies produced against two merozoite proteins that play important roles in erythrocyte invasion through a longitudinal study involving multiple sampling points of individuals living in a malaria endemic region
Summary
Despite the enormity of global financial commitment to malaria control[1,2], malaria is still considered endemic in 91 countries with an estimated 212 million cases and 429,000 deaths in 20153. The critical roles played by antibodies in protective immunity against malaria was first demonstrated by the classical studies of the 1960s6,7 and were confirmed later[8]. In this study we have investigated the changes in affinity over time of antibodies produced against two antigens that are targets of naturally-acquired immunity EBA175 (region RIII-V)[28] and Plasmodium falciparum Reticulocyte Homologue Protein 2 (PfRh2) (construct A9)[29]. EBAs and PfRh proteins play important cooperative roles in erythrocyte invasion[30] and EBA175 (RIII-V) and PfRh2 have been shown to elicit invasion inhibitory antibodies in rabbits and antibodies in humans living in malaria endemic areas have been associated with protective immunity[10,29,31,32,33]. Using isolates with genetic deletion of specific EBA proteins enables the investigation of antibodies to alternative invasion pathways utilized by P. falciparum[19,35,36]
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