Abstract
BackgroundMalaria kills almost 1 million people every year, but the mechanisms behind protective immunity against the disease are still largely unknown.Methodology/Principal FindingsIn this study, surface plasmon resonance technology was used to evaluate the affinity (measured as kd) of naturally acquired antibodies to the Plasmodium falciparum antigens MSP2 and AMA1. Antibodies in serum samples from residents in endemic areas bound with higher affinities to AMA1 than to MSP2, and with higher affinities to the 3D7 allele of MSP2-3D7 than to the FC27 allele. The affinities against AMA1 and MSP2-3D7 increased with age, and were usually within similar range as the affinities for the monoclonal antibodies also examined in this study. The finding of MSP2-3D7 type parasites in the blood was associated with a tendency for higher affinity antibodies to both forms of MSP2 and AMA1, but this was significant only when analyzing antibodies against MSP2-FC27, and individuals infected with both allelic forms of MSP2 at the same time showed the highest affinities. Individuals with the highest antibody affinities for MSP2-3D7 at baseline had a prolonged time to clinical malaria during 40 weeks of follow-up, and among individuals who were parasite positive at baseline higher antibody affinities to all antigens were seen in the individuals that did not experience febrile malaria during follow up.Conclusions/SignificanceThis study contributes important information for understanding how immunity against malaria arises. The findings suggest that antibody affinity plays an important role in protection against disease, and differs between antigens. In light of this information, antibody affinity measurements would be a key assessment in future evaluation of malaria vaccine formulations.
Highlights
Malaria is a parasitic infection that threatens almost half of the world’s population, with an estimated 243 million cases and around 863,000 deaths in 2008 [1]
The aim of this study was to increase the knowledge about the mechanisms behind the development of antibody-mediated protection against clinical malaria, by investigating whether there are differences in affinity between naturally acquired antibodies directed against different P. falciparum antigens, and whether affinity is associated with protection from symptoms of malaria
We have investigated affinity of naturally acquired antibodies in serum against two important immune targets and leading P. falciparum blood-stage vaccine candidates, Apical Membrane Antigen 1 (AMA1) and Merozoite Surface Protein 2 (MSP2)
Summary
Malaria is a parasitic infection that threatens almost half of the world’s population, with an estimated 243 million cases and around 863,000 deaths in 2008 [1]. The capability of controlling parasitemia in the blood is developed. The mechanisms underlying development of anti-disease immunity and the factors governing effective protection are still largely unknown. It is well established that antibodies contribute to protection against clinical malaria due to P. falciparum. Passive transfer of immunoglobulins from immune donors to individuals with P. falciparum infection reduced parasitemia and clinical symptoms [3,4]. Antibodies directed against cell surface proteins of either the merozoite form of the parasite or of infected red blood cells have been shown to be important components of acquired protective immunity against malaria [5]. Malaria kills almost 1 million people every year, but the mechanisms behind protective immunity against the disease are still largely unknown
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