Plasmodium falciparum merozoite surface protein 2: epitope mapping and fine specificity of human antibody response against non-polymorphic domains

Abstract

BackgroundTwo long synthetic peptides representing the dimorphic and constant C-terminal domains of the two allelic families of Plasmodium falciparum merozoite surface proteins 2 are considered promising malaria vaccine candidates. The aim of the current study is to characterize the immune response (epitope mapping) in naturally exposed individuals and relate immune responses to the risk of clinical malaria.MethodsTo optimize their construction, the fine specificity of human serum antibodies from donors of different age, sex and living in four distinct endemic regions was determined in ELISA by using overlapping 20 mer peptides covering the two domains. Immune purified antibodies were used in Western blot and immunofluorescence assay to recognize native parasite derivate proteins.ResultsImmunodominant epitopes were characterized, and their distribution was similar irrespective of geographic origin, age group and gender. Acquisition of a 3D7 family and constant region-specific immune response and antibody avidity maturation occur early in life while a longer period is needed for the corresponding FC27 family response. In addition, the antibody response to individual epitopes within the 3D7 family-specific region contributes to protection from malaria infection with different statistical weight. It is also illustrated that affinity-purified antibodies against the dimorphic or constant regions recognized homologous and heterologous parasites in immunofluorescence and homologous and heterologous MSP2 and other polypeptides in Western blot.ConclusionData from this current study may contribute to a development of MSP2 vaccine candidates based on conserved and dimorphic regions thus bypassing the complexity of vaccine development related to the polymorphism of full-length MSP2.Electronic supplementary materialThe online version of this article (doi:10.1186/1475-2875-13-510) contains supplementary material, which is available to authorized users.

Strain-transcending immune response generated by chimeras of the malaria vaccine candidate merozoite surface protein 2

“…Epitope-specific responses for animals immunized with full-length 3D7 and FC27 ( Fig. 3A,B ) were in agreement with the pattern of antigenicity described previously in mice, rabbits and in humans 18 38 39 . Robust responses were observed to conserved epitopes spanning the entire NTR, to multiple epitopes within the VRs of both MSP2 alleles, and to two distinct sequences within the CTR ( Fig.…”

Disordered epitopes as peptide vaccines

“…MSP2 also induces robust antibody responses when used as a vaccine, and these responses were shown to mediate protection in a Phase IIb trial in Papua New Guinea . The conformational and antigenic properties of MSP2 have been the subject of extensive study, providing important insights into the interplay between antigenicity and disorder, to which we will return in section 4 below.…”

“…Moreover, a key advantage afforded by peptide‐based approaches to vaccine development is the ability to omit ineffective regions such as these polymorphic regions entirely, ensuring that the response is focused on conserved epitopes that are more likely to elicit broadly protective responses. This is exemplified by the long synthetic peptides derived from the C‐terminal half of MSP2, which have been considered potential components of a malaria vaccine . These peptides include both conserved and dimorphic family‐specific sequences, but exclude the highly polymorphic regions of MSP2.…”

High-density Peptide Arrays Help to Identify Linear Immunogenic B-cell Epitopes in Individuals Naturally Exposed to Malaria Infection

“…The study conducted by Taylor et al described the dimorphic and polymorphic region and, to a lesser extent the conserved region as being detected by humoral responses (96). Recently, both the dimorphic and C-terminal domains were subjected to an epitope mapping which resulted in the description of antigenic peptides (102) with two of them overlapping with our data set (Fig. 2).…”