Saturday, October 31, 2009

RESA Peptides

Definition
RESA peptides are identical to the immunodominant T cell epitopes of the merozoite antigen, Pf155/RESA (ring-infected erythrocyte surface antigen). In cell culture experiments significant IgG secretion could be achieved with these peptides 1.

Related Peptides
RESA is deposited on the erythrocyte membrane has been considered an important vaccine candidate. Synthetic vaccines based on repeat sequences of malarial antigens have shown poor protection or inconsistent results during clinical trials. This has been attributed to lack of efficient T cell help or genetic restriction of the immune response at the host level. To overcome these limitations and to increase the immune response to peptide antigens, chimeric immunogens containing well defined Th determinant (CS.T3) with B cell antigenic sequences (RESA peptides) made by covalent linkage were synthesized 2.

Discovery
Chougnet et al., showed that two synthetic peptides representing major T cell epitopes from RESA protein, namely (EENVEHDA)4 and LGRSGGDIIKMQTL, induced the secretion of antibodies, reacting with the corresponding B cell epitope, as well as with RESA protein and the parasite, in cell culture supernatants 3.

Structural Characteristics
The P. falciparum antigen Pf155/RESA, which is deposited in the erythrocyte membrane during merozoite invasion, is considered to be a candidate for a blood-stage vaccine. The C-terminal part of Pf155/RESA comprises a region of repeated subunits of eight, four, or three amino acids. The octapeptide subunit EENVEHDA is immunogenic in rabbits, and a large fraction of human antibodies to Pf155/RESA also react with this linear sequence, suggesting that the octapeptide is part of a major antigenic region of Pf155/RESA4. RESA protein contains three tandemly repeated immunodominant B cell epitopes viz EENV, EENVEHDA and DDEHVEEPTVA. These peptides are found to be antigenically dominant and antibodies raised against them have been shown to inhibit merozoite invasion of RBCs 2.

Mode of Action
RESA peptide mediated protection is correlated with the presence of serum reactivity with the Pf155/RESA peptides leading to the production of antibodies 3.

Functions
RESA peptides are found to be antigenically dominant and antibodies raised against them have been shown to inhibit merozoite invasion of RBCs 2.

References
1. Fievet N, Chougnet C, Dubois B, Deloron P (1993). Quantification of antibody-secreting lymphocytes that react with Pf155/RESA from Plasmodium falciparum: an ELISPOT assay for field studies. Clin Exp Immunol., 91(1):63-67.
2. Rao DN, Chaba B, Kumar P, Haq W, Sabhnani L (1997). Developing peptide based immunogen against human malaria delivered in liposomes containing non-toxic adjuvants. Indian Journal of Clinical Biochemistry, 12:52-54.
3. Chougnet C, Troye-Blomberg M, Deloron P (1991). Human immune response in Plasmodium falciparum malaria: synthetic peptides corresponding to known epitopes of the Pfl 55/RESA antigen induce production of parasite specific antibody in vitro. J Immunol., 147:2295-2301.
4. Sjölander A, Ståhl S, Nygren PA, Aslund L, Ahlborg N, Wåhlin B, Scherf A, Berzins K, Uhlén M, Perlmann P (1990). Anders Sjolander et al., 1990. Immunogenicity and Antigenicity in Rabbits of a Repeated Sequence of Plasmodium falciparum Antigen Pf155/RESA Fused to Two Immunoglobulin G-Binding Domains of Staphylococcal Protein. Infect Immun., 58(4):854-859.

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