The antibody response to Plasmodium falciparum Merozoite Surface Protein 4: Comparative assessment of specificity and growth inhibitory antibody activity to infection-acquired and immunization-induced epitopes

Harini D De Silva, Suha M Saleh, Svetozar Kovacevic, Lina Wang, Casilda G Black, Magdalena Plebanski, Ross L Coppel

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Abstract

Malaria remains a global public health challenge. It is widely believed that an effective vaccine against malaria will need to incorporate multiple antigens from the various stages of the parasite s complex life cycle. Plasmodium falciparum Merozoite Surface Protein 4 (MSP4) is a vaccine candidate that has been selected for development for inclusion in an asexual stage subunit vaccine against malaria. METHODS: Nine monoclonal antibodies (Mabs) were produced against Escherichia coli-expressed recombinant MSP4 protein and characterized. These Mabs were used to develop an MSP4-specific competition ELISA to test the binding specificity of antibodies present in sera from naturally P. falciparum-infected individuals from a malaria endemic region of Vietnam. The Mabs were also tested for their capacity to induce P. falciparum growth inhibition in vitro and compared against polyclonal rabbit serum raised against recombinant MSP4 RESULTS: All Mabs reacted with native parasite protein and collectively recognized at least six epitopes. Four of these Mabs recognize reduction-sensitive epitopes within the epidermal growth factor-like domain found near the C-terminus of MSP4. These sera were shown to contain antibodies capable of inhibiting the binding of the six Mabs indicating infection-acquired responses to the six different epitopes of MSP4. All of the six epitopes were readily recognized by human immune sera. Competition ELISA titres varied from 20 to 640, reflecting heterogeneity in the intensity of the humoral response against the protein among different individuals. The IgG responses during acute and convalescent phases of infection were higher to epitopes in the central region than to other parts of MSP4. Immunization with full length MSP4 in Freund s adjuvant induced rabbit polyclonal antisera able to inhibit parasite growth in vitro in a manner proportionate to the antibody titre. By contrast, polyclonal antisera raised to individual recombinant f
Original languageEnglish
Pages (from-to)1 - 12
Number of pages12
JournalMalaria Journal
Volume10
Issue numberArt. No: 266
DOIs
Publication statusPublished - 2011

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