Merozoite surface protein 2 allelic variation influences the specific antibody response during acute malaria in individuals from a Brazilian endemic area

Abstract

The antibody response to Plasmodium falciparum parasites of naturally infected population is critical to elucidate the role of polymorphic alleles in malaria. Thus, we evaluated the impact of antigenic diversity of repetitive and family dimorphic domains of the merozoite surface protein 2 (MSP-2) on immune response of 96 individuals living in Peixoto de Azevedo (MT-Brazil), by ELISA using recombinant MSP-2 proteins. The majority of these individuals were carrying FC27-type infections. IgG antibody responses were predominantly directed to FC27 parasites and were correlated to the extension of polymorphism presented by each MSP-2 region. This finding demonstrated the impact of the genetic polymorphism on antibody response and therefore, its importance on malaria vaccine efficacy.Key words: Plasmodium falciparum -merozoite surface protein-2 -antibody response -antigenic polymorphism -malaria It has been suggested that the genetic variability of the parasite could allow its evasion from immune responses induced by previous infections with parasites expressing variant antigenic forms. Genetic modifications in antigenic epitopes could induce conformational changes in the polypeptide structure resulting in the lack of putative reactive sites at the protein surface, as well as in different presentation of these sites to the immune system (Ranford-Cartwright et al. 1996, Tonhosolo et al. 2001, Kanunfre et al. 2003. Consequently, studies on the relationship of genetic diversity of B epitopes in parasite surface antigens and its impact on the recognition of antibodies generated during natural infections should be carried out for designing immunization strategies.The genetic polymorphism of the merozoite surface protein 2 (MSP-2) of Plasmodium falciparum has been studied due to its applicability as a target for a malaria vaccine development and its putative association with antibody-mediated protection (Taylor et al. 1995, Genton et al. 2003, Scopel et al. 2006). The MSP-2 allelic families -known as ICI/3D7 and FC27 -corresponding, respectively to two antigenically distinct serogroups: A and B, which are frequently and strongly recognized by antibodies from malaria-exposed individuals (Fenton et al. 1990, Ekala et al. 2002. These antibodies are preferably directed against the central variable region of the molecule, which is composed by tandem repeats blocks (R1 and R2) flanked by family dimorphic blocks. The FC27 family has shown different numbers of the relatively conserved R1 (32-mer) and R2 (12-mer) repetitive regions. The R1 repeats of 3D7 family, characterized by shorter sequence repeats of 3 to 10 residues, can vary considerably although they are usually glycine, serine and alanine rich, while the R2 region is a well conserved repeat rich in the amino acid threonine. It has been suggested that naturally immunodominant epitopes are encoded within the repetitive sequences of the molecule (Smythe et al.1990).Our group previously identified (Sallenave-Sales et al. 2003) polymorphic alleles from both MSP-2 families in P....

Genetic diversity and antibody responses against Plasmodium falciparum vaccine candidate genes from Chhattisgarh, Central India: Implication for vaccine development

“…The asexual blood stage antigens i.e. pfmsp1 , pfmsp2 and the ring –infected erythrocyte surface antigen (RESA) are combination vaccine known as combination B, which is immunogenic [ 41 , 42 ] and detected a significant immune response against the central variable region of the pfmsp2 . In addition, both FC27 and 3D7 family were associated with the extensive polymorphism and immune response.…”

Role of Tumour Necrosis Factor (TNF) and Glycosylphosphatidylinositol (GPI) as Important Mediators in the Pathogenesis of Malaria Infection

“…A study previously identified polymorphic alleles from both MSP-2 families in Plasmodium falciparum isolates 26 . A recent study evaluated the impact of antigenic diversity of repetitive and family dimorphic domains of the merozoite surface protein 2 (MSP-2) on immune response by ELISA using recombinant MSP-2 proteins 27 .…”