Avaliação da modulação da resposta imune induzida por vacina contra tuberculose: rBCG-CMX

• Autor(a) principal: Costa, Adeliane Castro da
• Data de Publicação: 2016
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/5550
• topic: Tuberculose; Vacinas; BCG; rBCG-CMX; Tuberculosis; Vaccine; BCG; rBCG-CMX; CIENCIAS BIOLOGICAS::IMUNOLOGIA

In the first chapter of this thesis we demonstrate, in a review article, some of the successful strategies employed in the construction of Bacillus Calmette-Guérin (BCG) vaccines, among others being: overexpression of promising Mycobacterium tuberculosis (Mtb) immunodominant antigens already expressed by BCG introduction of Mtb immunodominant antigens not expressed by BCG, such as antigens in the regions of difference (RD) 1 thru 16; combination of overexpression and introduction of novel antigens to BCG; BCG modification to skew immune response toward TCD8+, as for example recombinant BCG (rBCG) expressing cytokines. In the second chapter, we demonstrate that the recombinant fusion protein CMX is capable of aggregating important immunogenic properties to vaccine vectors, by inducing an effective response for the control of Mtb infection in the mouse tuberculosis infection model. It is hypothesized that the introduction of the rCMX protein in the BCG vaccine could add immunological properties that are absent in BCG, thus leading to the induction of important cell populations for the control of Mtb infection. Our results demonstrate that the introduction of the rCMX in the BCG vaccine, resulting the recombinant BCG vaccine (rBCG-CMX) was an important factor for the observed Th1 and Th17 responses, as well as polyfunctional cells, that could be responsible for the reduced inflammatory lesions seen in the lungs of Mtb infected BALB/c mice, significantly reducing the bacillary load in comparison to in comparison to mice immunized with BCG Moreau vaccine. Lastly, in the third chapter of this thesis we propose that rCMX protein could be responsible for modulating the BCG vaccine to activate a more adequate and protective innate immunity. Our results show that the rBCG-CMX vaccine induces the activation of alveolar macrophages by means of expression of activation-associated molecules CD86 and CD206. The increase in the expression of those molecules are accompanied by the production of TGF-β e IL-1α which in turn could be responsible for the decreased necrosis and higher apoptosis induction promoted by rBCG-CMX vaccination. This phenomenon could be providing a higher cellular survival rate of the recombinant vaccine, leading to a better processing and presentation by MHC-II. As rCMX was shown to induce the production of IL-1α, IL-6 e TGF-β by a pathway that seems to involve the participation of TLR-4, we hypothesize that this recombinant protein could be modulating the BCG vaccine to induce a more appropriate and protectiveresponse for Mtb infection.