Avaliação da atividade adjuvante da subunidade B recombinante da enterotoxina termolábil de Escherichia coli fusionada ou co-administrada a rFimA de Salmonella Enteritidis

Abstract

The association of vaccine antigens to potent immunological adjuvants is a key strategy to improve the performance of subunit vaccines. Adjuvants are components that, when used in combination with a specific antigen, induce more immunity that the antigen alone. Microbial products have been used as adjuvant, including the B subunit of the thermo labile entherotoxin of Escherichia coli (LTB), which is atoxic. LTB is known by its great efficiency as mucosal immunity adjuvant and this activity depends on the shape of the antigen combination (co-administered or fused), on the immunization route (mucosal or parentheral) and the dosage. This study aims to evaluate the adjuvant activity of recombinant LTB (rLTB), both as chimeric and coadministered orally or intramuscularly, using the major fimbrial unit type 1 (FimA) of Salmonella Enteritidis as antigen. BALB/c mice were immunized orally or intramuscularly with three doses of rLTB or PBS (controls) or rFimA, rFimA associated with Freund's incomplete adjuvant (rFimA+AI, i.m. immunized animals), co-administered or fused to LTB (chimera). The levels of total systemic antibodies, IgG1, IgG2a and IgA anti-rFimA were measured by ELISA and an animal protection assay against S. Typhimurium infection was performed. The results show that rLTB only showed adjuvant activity that resembled the commercial adjuvant when coadministered intramuscularly to rFimA and for totals antibody production. These results confirm that the action of adjuvant rLTB is influenced by the shape of binding to the antigen (fused or co-administered) and route of administration. Immunizations did not induce protection of mice challenged with S. Typhimurium, but survival time was greater among animals immunized with only the rFimA and rFimA+AI. Furthermore, the total antibody titer, IgG1 and IgG2a obtained by the chimeric form, both orally as intramuscularly, were similar to those obtained by the animal only immunized with rFimA. These results suggest that rFimA has a possibility of having an adjuvant capability rFimA.