Avaliação da modulação da resposta imune induzida por vacina contra tuberculose: rBCG-CMX
Nenhuma Miniatura disponível
Data
2016-03-01
Autores
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Federal de Goiás
Resumo
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.
Descrição
Palavras-chave
Citação
COSTA, A. C. Avaliação da modulação da resposta imune induzida por vacina contra tuberculose: rBCG-CMX. 2016. 143 f. Tese (Doutorado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2016.