Identificação de epitopos imunogêncos de Shigella flexneri

Abstract

Shigella sp. is responsible for one of the leading causes of child morbidity and mortality, especially in developing countries. Infection by this bacterium is known as shigellosis or bacillary dysentery, a highly contagious inflammatory diarrhea. Antibiotic therapy against shigellosis has become a challenge due to the increasing resistance to antibiotics presented by clinical isolates. Thus, immunoprophylaxis directed towards the development of vaccines has become a priority for the World Health Organization in the fight against shigellosis. Considering the need to develop new vaccination strategies for the control of shigellosis and the absence of a licensed and safe vaccine, the present work proposed to identify B cell epitopes of the OmpA and FimH proteins of Shigella flexneri with immunogenic potential, using in silico analyzes for the prediction, besides evaluating the humoral response of mice immunized with synthetic peptides that mimic these epitopes. Through the IEDB program, 11 epitopes (5 for OmpA and 6 for FimH) were predicted and the corresponding peptides were synthesized. The 3D structure of these antigens was also constructed to facilitate the prediction of epitopes. Peptides that reacted to the anti-Shigella antiserum were selected for immunization of immunocompetent mice. The anti-peptide antisera P1 (positive control), P2, P3 and P4 were produced and tested against 13 wild isolates of Shigella flexneri, and showed 92.3% (12/13) of recognition by the corresponding epitope in the native protein present in the strains Tested. The most immunodominant epitope was P2 with a statistically significant result (P <0.0422), when the level of recognition of P2 was compared with P1, significant differences were also observed (P <0.0155). The P4 epitope was the second immunodominant epitope and is located in one of the loops on the surface of the OmpA, whereas the P2 epitope which was the most immunodominant is located in the globular domain in the periplasmic space. However, the antibodies produced against the P2 and P4 peptides were able to recognize wild isolates of S. flexneri, this result makes it possible to infer that these peptides have potential for a vaccine candidate.