Elsevier

Acta Tropica

Volume 114, Issue 3, June 2010, Pages 138-143
Acta Tropica

Review
Erythrocyte invasion and functionally inhibitory antibodies in Plasmodium falciparum malaria

https://doi.org/10.1016/j.actatropica.2009.05.017Get rights and content

Abstract

Malaria is a disease that kills several million people every year. P. falciparum merozoites invade new erythrocytes every 48 h, causing fever, anemia and cerebral malaria. Effective immunity against malaria develops slowly and only after repeated exposure. Antibodies are an important part of this immunity. However, the antigens that mediate immunity by inducing functionally imperative antibodies have not yet been identified. This review gives an overview of the erythrocyte invasion process, which has been described to include several different antigens. Invasion inhibitory antibodies can inhibit merozoite penetration of new erythrocytes, and different methods for measurement of the presence of functionally important antibodies have been employed. ELISA, Invasion inhibition assays and ADCI are some of the methods discussed.

Introduction

The symptoms of malaria include fever, neurological symptoms and cerebral malaria. During blood stage replication P. falciparum merozoites invade new erythrocytes every 48 h, which often leads to severe anemia. Effective immunity against malaria develops slowly and only after repeated exposure to the parasites (Marsh and Kinyanjui, 2006), and the emergence of resistance to the drugs used to treat malaria has indicated that a vaccine would be of importance as a sustainable, long-term solution. However, the antigens that mediate immunity by inducing functionally important antibodies have not yet been identified.

Section snippets

Merozoite antigens involved in invasion

The actions by which merozoites recognize, attach to, and enter erythrocytes represent a very efficient process that takes only about a minute to occur (Gilson and Crabb, 2009). Erythrocyte invasion involves multiple receptor–ligand interactions, and a number of merozoite proteins have proposed or established roles in invasion (Cowman and Crabb, 2006, Miller et al., 2002). It is presumed that components of the initial attachment include antigens on the surface of the merozoite, such as

The role of antibodies in P. falciparum malaria

As early as the 1960s, it was shown that antibodies from humans can reduce parasitemia and clear clinical symptoms (Cohen et al., 1961, Edozien et al., 1962). Moreover, it is known that antibodies are transferred to the fetus during pregnancy, and newborn babies very rarely contract malaria during their first weeks of life (Akum et al., 2005). It has also been observed that the antibodies present in maternal blood and those in cord blood show very good correlation with regard to

Methods used to measure antibodies

Standard ELISAs do not account for the epitope specificity or affinity of antibodies that are essential for functional activity. Novel methods such as microarrays using proteins made in a cell-free system are now being employed to evaluate new antigens, but, despite these efforts, there is still no information in such a system about the function of the antibodies (Doolan et al., 2008). Transgenic parasites can be used in invasion inhibition assays to circumvent some of these problems (Persson

Conclusion

There is a need for functional assays, as there is usually poor correlation between the presence of invasion-inhibiting antibodies and antibodies detected by ELISA. We have found that when performing an invasion inhibition assay, it is preferable to use dialyzed sera, two cycles of invasion, and dihydroethidine and flow cytometry to evaluate parasitemia. However, more studies in basic immunology are needed to determine how immunity against malaria arises, and what functional aspects of the

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