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Shortening and modifying the 1513 MSP-1 peptide’s α-helical region induces protection against malaria

2004; Elsevier BV; Volume: 315; Issue: 2 Linguagem: Inglês

10.1016/j.bbrc.2004.01.072

1090-2104

Fabiola Espejo, Adriana Bermúdez, Elizabeth Aparecida Ferraz da Silva Torres, Mauricio Urquiza, Raúl Rodrı́guez, Yolanda López, Manuel E. Patarroyo,

Invertebrate Immune Response Mechanisms

Immunogenic and protective peptide sequences are of prime importance in the search for an anti-malarial vaccine. The MSP-1 conserved and semi-conserved sequences have been shown to contain red blood cell (RBC) membrane high affinity binding peptides (HABP). HABP 1513 sequence (42GYSLFQKEKMVLNEGTSGTA61), from this protein's N-terminal, has been shown to possess a T-epitope; however, it did not induce a humoral immune response or complete protection when evaluated in Aotus monkeys. Analogue peptides with critical binding residues replaced by amino acids with similar mass but different charge were synthesised and tested for immunogenicity and protectivity in monkey. NMR studies correlated structural behaviour with biological function. Non-immunogenic and non-protective 1513 native peptide presented a helical fragment between residues L4 and E14. C-terminal, 5-residue-shorter, non-immunogenic, non-protective peptide 17894 contained an α-helix from Q6 to L12 residues. Immunogenic and protective peptide 13946 presented a shorter α-helix between K7 to N13 residues. These data suggest that changing certain residues permits better peptide fit within the MHC class II–peptide–TCR complex, thus activating the immune system and inducing a protective immune response.