RESUMO
Synthetic vaccines constitute the most promising tools for controlling and preventing infectious diseases. When synthetic immunogens are designed from the pathogen native sequences, these are normally poorly immunogenic and do not induce protection, as demonstrated in our research. After attempting many synthetic strategies for improving the immunogenicity properties of these sequences, the approach consisting of identifying high binding motifs present in those, and then performing specific changes on amino-acids belonging to such motifs, has proven to be a workable strategy. In addition, other strategies consisting of chemically introducing non-natural constraints to the backbone topology of the molecule and modifying the α-carbon asymmetry are becoming valuable tools to be considered in this pursuit. Non-natural structural constraints to the peptide backbone can be achieved by introducing peptide bond isosters such as reduced amides, partially retro or retro-inverso modifications or even including urea motifs. The second can be obtained by strategically replacing L-amino-acids with their enantiomeric forms for obtaining both structurally site-directed designed immunogens as potential vaccine candidates and their Ig structural molecular images, both having immuno-therapeutic effects for preventing and controlling malaria.
Assuntos
Vacinas Antimaláricas , Peptidomiméticos , Animais , Haplorrinos , Humanos , Vacinas Antimaláricas/síntese química , Vacinas Antimaláricas/química , Vacinas Antimaláricas/imunologia , Vacinas Antimaláricas/farmacologia , Malária Falciparum/imunologia , Malária Falciparum/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Peptidomiméticos/síntese química , Peptidomiméticos/química , Peptidomiméticos/imunologia , Peptidomiméticos/farmacologia , Vacinas de Subunidades Antigênicas/síntese química , Vacinas de Subunidades Antigênicas/química , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/farmacologia , Vacinas Sintéticas/química , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/farmacologiaRESUMO
We have developed monoclonal antibodies directed against the pseudopeptide psi-130, derived from the highly conserved malarial antigen Plasmodium falciparum merozoite surface protein 2 (MSP-2), for obtaining novel molecular tools with potential applications in the control of malaria. Following isotype switching, these antibodies were tested for their ability to suppress blood-stage parasitemia through passive immunization in malaria-infected mice. Some proved totally effective in suppressing a lethal blood-stage challenge infection and others reduced malarial parasitemia. Protection against P. berghei malaria following Ig passive immunization can be associated with specific immunoglobulins induced by a site-directed designed MSP-2 reduced amide pseudopeptide.