Desenvolvimento de um modelo de vacinação contra Toxoplasma Gondii utilizando Corynebacterium pseudotuberculosis atenuadas recombinantes como veículo para a apresentação de antígenos

Abstract

Toxoplasmosis is a worldwide disease and its etiologic agent is the protozoan intracellular parasite Toxoplasma gondii. The disease presents a clinical picture that varies from asymptomatic infections to extremely serious systemic manifestations. In livestock, congenital transmission can cause significant losses due to abortions, stillbirths, fetal malformations and birth of weak lambs and despite the high rates of infection there is still no treatment able to eradicate the parasite or truly effective vaccines that could protect against its infections. In an attempt to generate a bivalent vaccine against this disease as well as against caseous lymphadenitis, another disease that also affects ovine and caprine herds and is caused by the bacteria Corynebacterium pseudotuberculosis, the attenuated T1 strain of C. pseudotuberculosis was used in this work as a live vector for the expression of T. gondii SAG2 antigen. In Western Blotting assays it was possible to detect the expression of SAG2 by C. pseudotuberculosis (CpSAG2). SAG2-recombinant bacteria and adenoviruses (AdSAG2) were used to immunize BALB/c mice with homologous and heterologous prime-boost protocols. CpSAG2 and AdSAG2 were able to stimulate a humoral response in all vaccinated groups, generating antibodies that reacted with T. gondii lysate antigen (TLA) as well as with SAG2 itself, as detected by ELISA and Western blotting assays, respectively. The results demonstrate the correct expression of SAG2 in vivo by the attenuated T1 strain as well as the immunogenicity of this bivalent vaccine candidate, in particular when used in heterologous prime-boost regimes, making of this microrganism a promissing live vector for the generation of vaccinal formulations against these as well as other diseases with similar characteristics.