RESUMEN
Six peptides, A, B1, B, C, D and E, derived from the primary sequence of Schistosoma mansoni glyceraldehyde 3-phosphate dehydrogenase (SG3PDH) were selected based on lowest homology to human glyceraldehyde 3-P dehydrogenase (G3PDH), multimerized in dipeptidic multiple antigen peptide (D-MAP) constructs and used for the immunization of BALB/c mice. Tetrabranched D-MAPs A-B, B1-C and D-E and the bis-D-MAP B-E elicited strong cell-mediated and antibody responses against immunogen, unit peptides and their cognate sequences in the native and denatured protein. D-MAP A-B induced protection against challenge infection. Immunization with D-MAP B1-C failed to affect the challenge worm parameters, probably because peptides B1 and C, previously shown to elicit immune responses associated with increase and decrease in challenge worm fertility, respectively, induced immune responses with opposing effects when combined in a D-MAP construct. A similar suggestion may explain the failure of D-MAP D-E to protect the host against challenge infection. In contrast, immunization with D-MAP B-E resulted in robust protection of the host, possibly because it contains peptides known to evoke immune responses associated with a significant decrease in challenge worm burden and fertility. The data together suggest that the specificity, not the quantity, of the induced immune responses is the determining factor for the efficacy of synthetic peptide-based vaccine for schistosomiasis.
Asunto(s)
Antígenos Helmínticos/genética , Gliceraldehído-3-Fosfato Deshidrogenasas/inmunología , Schistosoma mansoni/enzimología , Schistosoma mansoni/inmunología , Secuencia de Aminoácidos , Animales , Anticuerpos Antihelmínticos/biosíntesis , Antígenos Helmínticos/química , Femenino , Gliceraldehído-3-Fosfato Deshidrogenasas/química , Gliceraldehído-3-Fosfato Deshidrogenasas/genética , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/inmunología , Schistosoma mansoni/genética , Esquistosomiasis mansoni/inmunología , Esquistosomiasis mansoni/parasitología , Esquistosomiasis mansoni/prevención & control , Vacunas/genética , Vacunas/aislamiento & purificaciónRESUMEN
Schistosoma mansoni glyceraldehyde 3-phosphate dehydrogenase (SG3PDH) is a target of cellular and humoral immune responses of Brazilian and Egyptian subjects putatively resistant to reinfection with S. mansoni. In an aim to develop a safe, stable and effective vaccine based on this promising molecule, six peptides derived from its primary sequence were selected based on the lowest homology to human G3PDH. The synthetic peptides were tested by ELISA against plasma of humans putatively susceptible or resistant to reinfection with S. mansoni or S. haematobium following chemotherapeutic cure of previous infection. Repeat experiments indicated that the six peptides bear human B-cell epitopes that bind immunoglobulin (Ig)M, IgG1 and IgG3 antibodies. Resistance to reinfection appeared to be significantly associated with humoral immune responses to multiple peptides. This contention was supported by studies in the murine model, whereby we examined the B cell immune responses of Swiss and inbred BALB/c and C57BL/6 mice immunized with recombinant SG3PDH (rSG3PDH) to the six SG3PDH-derived peptides. The serum antibodies of rSG3PDH-immunized Swiss mice were directed to only one of the six peptides tested by ELISA. Antibodies from rSG3PDH-immunized C57BL/6 and BALB/c mice bound, respectively, to four and six out of six peptides. In contrast to Swiss mice, immunization of C57BL/6 and BALB/c mice with rSG3PDH induced protection against challenge cercariae which reached the level of significance (P < 0.05) for BALB/c mice. The data together indicate that host recognition of multiple peptides of a candidate vaccine antigen is necessary for the expression of its ability to contribute to protective immunity against Schistosomiasis.