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. 2009 Mar;77(3):1189-96.
doi: 10.1128/IAI.00780-07. Epub 2009 Jan 12.

Evidence for multiple B- and T-cell epitopes in Plasmodium falciparum liver-stage antigen 3

Aissatou Toure-Balde  1 , Blanca-Liliana Perlaza, Jean-Pierre Sauzet, Mouhamadou Ndiaye, Georgette Aribot, Adama Tall, Cheikh Sokhna, Christophe Rogier, Giampietro Corradin, Christian Roussilhon, Pierre Druilhe
Affiliations

Evidence for multiple B- and T-cell epitopes in Plasmodium falciparum liver-stage antigen 3

Aissatou Toure-Balde et al. Infect Immun. 2009 Mar.

Abstract

Liver-stage antigen 3 (LSA-3) is a new vaccine candidate that can induce protection against Plasmodium falciparum sporozoite challenge. Using a series of long synthetic peptides (LSP) encompassing most of the 210-kDa LSA-3 protein, a study of the antigenicity of this protein was carried out in 203 inhabitants from the villages of Dielmo (n = 143) and Ndiop (n = 60) in Senegal (the level of malaria transmission differs in these two villages). Lymphocyte responses to each individual LSA-3 peptide were recorded, some at high prevalences (up to 43%). Antibodies were also detected to each of the 20 peptides, many at high prevalence (up to 84% of responders), and were directed to both nonrepeat and repeat regions. Immune responses to LSA-3 were detectable even in individuals of less than 5 years of age and increased with age and hence exposure to malaria, although they were not directly related to the level of malaria transmission. Thus, several valuable T- and B-cell epitopes were characterized all along the LSA-3 protein, supporting the antigenicity of this P. falciparum vaccine candidate. Finally, antibodies specific for peptide LSP10 located in a nonrepeat region of LSA-3 were found significantly associated with a lower risk of malaria attack over 1 year of daily clinical follow-up in children between the ages of 7 and 15 years, but not in older individuals.

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Figures

FIG. 1.
FIG. 1.
Schematic representation of the Plasmodium falciparum LSA-3 protein showing the localization of the peptides employed, the 17 long synthetic peptides (LSP1 to LSP17) and the 3 smaller peptides (LSA-3-NRI, LSA-3-NRII, and LSA-3-RE) encompassing most of the LSA-3 protein. The localization of DG729 is indicated. The numbers are amino acid positions.
FIG. 2.
FIG. 2.
Prevalence of individuals having antibodies to the LSA-3-Re repeat and trend for increase with age in the mean levels of antibodies in Dielmo, Senegal. The percentages of responders to LSA-3-Re (A) and the mean levels of antibody responses to LSA-3-Re antigen (B) are shown for various age groups (age in years). The total number of villagers tested was 143, and the number of individuals included in each age group is the same as that indicated in Table 1. The bars in panel A correspond to 95% confidence intervals of the percentages, and the bars in panel B correspond to standard deviations.
FIG. 3.
FIG. 3.
Levels of antibody responses to the 17 different LSP encompassing the LSA-3 protein in different age groups of inhabitants of the Dielmo and Ndiop villages in Senegal. The numbering of the different LSP tested correspond to that shown in Fig. 1, i.e., they are indicated from the N terminus to the C terminus of LSA-3. The absorbance values (AU) indicated in the figure correspond to the difference between test OD values minus the mean of the control OD values plus 3 SD.
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