Open Access Research

Anti-Plasmodium falciparum invasion ligand antibodies in a low malaria transmission region, Loreto, Peru

Elizabeth Villasis1, Mary Lopez-Perez2, Katherine Torres1, Dionicia Gamboa13, Victor Neyra1, Jorge Bendezu1, Nancy Tricoche2, Cheryl Lobo4, Joseph M Vinetz135* and Sara Lustigman2*

Author Affiliations

1 Malaria Laboratory, Instituto de Medicina Tropical “Alexander von Humboldt”, Universidad Peruana Cayetano Heredia, Lima, Peru

2 Molecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, NYC, New York, NY, USA

3 Departamento de Ciencias Celulares y Moleculares, Facultad de Ciencias y Filosofia, Universidad Peruana Cayetano Heredia, Lima, Peru

4 Blood-Borne Parasites, Lindsley F. Kimball Research Institute, New York Blood Center, NYC, New York, NY, USA

5 Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, CA, USA

For all author emails, please log on.

Malaria Journal 2012, 11:361  doi:10.1186/1475-2875-11-361

Published: 30 October 2012

Abstract

Background

Erythrocyte invasion by Plasmodium falciparum is a complex process that involves two families; Erythrocyte Binding-Like (EBL) and the Reticulocyte Binding-Like (PfRh) proteins. Antibodies that inhibit merozoite attachment and invasion are believed to be important in mediating naturally acquired immunity and immunity generated by parasite blood stage vaccine candidates. The hypotheses tested in this study were 1) that antibody responses against specific P. falciparum invasion ligands (EBL and PfRh) differ between symptomatic and asymptomatic individuals living in the low-transmission region of the Peruvian Amazon and 2), such antibody responses might have an association, either direct or indirect, with clinical immunity observed in asymptomatically parasitaemic individuals.

Methods

ELISA was used to assess antibody responses (IgG, IgG1 and IgG3) against recombinant P. falciparum invasion ligands of the EBL (EBA-175, EBA-181, EBA-140) and PfRh families (PfRh1, PfRh2a, PfRh2b, PfRh4 and PfRh5) in 45 individuals infected with P. falciparum from Peruvian Amazon. Individuals were classified as having symptomatic malaria (N=37) or asymptomatic infection (N=8).

Results

Antibody responses against both EBL and PfRh family proteins were significantly higher in asymptomatic compared to symptomatic individuals, demonstrating an association with clinical immunity. Significant differences in the total IgG responses were observed with EBA-175, EBA-181, PfRh2b, and MSP119 (as a control). IgG1 responses against EBA-181, PfRh2a and PfRh2b were significantly higher in the asymptomatic individuals. Total IgG antibody responses against PfRh1, PfRh2a, PfRh2b, PfRh5, EBA-175, EBA-181 and MSP119 proteins were negatively correlated with level of parasitaemia. IgG1 responses against EBA-181, PfRh2a and PfRh2b and IgG3 response for PfRh2a were also negatively correlated with parasitaemia.

Conclusions

These data suggest that falciparum malaria patients who develop clinical immunity (asymptomatic parasitaemia) in a low transmission setting such as the Peruvian Amazon have antibody responses to defined P. falciparum invasion ligand proteins higher than those found in symptomatic (non-immune) patients. While these findings will have to be confirmed by larger studies, these results are consistent with a potential role for one or more of these invasion ligands as a component of an anti-P. falciparum vaccine in low-transmission malaria-endemic regions.

Keywords:
Antibodies; Invasion; Plasmodium falciparum; Malaria; Peru