Dados do Trabalho

Título

Design of a pan-specific anti-leishmaniasis vaccine

Introdução

Several research groups have made numerous contributions to the field of anti-leishmaniasis vaccine development. However, none of these prototype vaccines have been licensed for use in humans.

Objetivo (s)

The aim of this work is to develop a poly-epitope prototype vaccine that induces a protective, well-modulated and pan-specific immune response.

Material e Métodos

Epitopes were screened from proteins previously selected from the L. naiffi and L. amazonensis proteomes. Proteins with a low rate of evolution, a higher number of conserved domains and a higher antigenicity score were selected by in silico analysis. The selected sequences were fully synthesised as a peptide library of 15 amino acids in cellulose membrane. These peptides were screened with serum pools from patients cured of cutaneous leishmaniasis. Seventeen epitopes with high binding affinity to IgG present in the sera were selected. These epitopes were analysed separately in silico for evolutionary and functional conservation. They were also evaluated for similarity in the human, dog and hamster proteomes.

Resultados e Conclusão

Fifteen epitopes were selected to be fused to two innocuous protein sequences to form chimeras. Variations of these sequences were then designed with the inclusion of the adjuvant peptide. These sequences exhibited the desired stability and conformation of the secondary and tertiary structures in silico, hydrophobicity in most of the sequence, lack of structural and functional similarity to proteins from vertebrate hosts and Leishmania. The chimeras also showed antigenicity scores above the cut-off and immunodominance (assessed in silico by predicting binding to BCR and HLA classes I and II).

Palavras-chave

epitope screening, vaccine prototype, leishmaniasis

Agradecimentos

LIPMED (ioc/Fiocruz), CDTS (Fiocruz), PPGMT (Fiocruz), CNPq, CAPES, FAPERJ, Fiocruz