Desenvolvimento vacinal para prevenção e controle da brucelose

Abstract

Brucellosis is one of the major zoonotic infectious diseases that results in significant economic losses for animals production. The control and prevention of animal brucellosis are largely based on vaccination with live attenuated strains. Initially, meta-analysis studies were conducted addressing the subject of Brucella vaccinology in mice and preferred natural hosts, aiming to evaluate the protection index of different vaccine categories and the influence of several variables on vaccine protection. The meta-analysis in the murine model studied 117 publications of experimental vaccines indexed in PubMed, in total 782 experiments analyzed, which demonstrated in the temporal analysis that there was no improvement in protection indexes over the last three decades. The meta-regression model developed included the categories of vaccines (attenuated, DNA, inactivated, mutant, subunit and vector) considering the protection index as the dependent variable and the other parameters (mouse lineage, vaccination route, number of vaccinations, use of adjuvant, challenge with Brucella species) as independent variables. Subunit and vectorized vaccines provided significantly lower protection rates when compared to attenuated vaccines, and other variables positively influenced the protection index, such as two immunizations and challenge with B. melitensis, B. ovis and B. suis, on the other hand, the use of adjuvant had no significant effect on the protection index. The meta-analysis study in natural hosts evaluated 45 publications indexed in PubMed and Scopus, representing 116 individual experiments. The value of risk difference, calculated based on the prevention of abortions and infection in organs of immunized and non-immunized animals, was adopted as a protection measure. The temporal analysis in this study demonstrated that there were no improvements in vaccine protection in the last decades. The meta-regression model developed for the natural hosts included the vaccine categories (attenuated, inactivated, mutant, subunit and vectorized) considering the value of risk difference as the dependent variable, and some variables demonstrated to influence vaccine protection, such as the subcutaneous route of vaccination was significantly more protective than the intramuscular and oral route, and the subcutaneous route provided a higher risk difference value than the conjunctival route when used in the challenge. Subunit vaccines provided significantly less protection, while inactivated vaccines were more protective than attenuated vaccines. A study was carried out evaluating the mutant strain B. ovis abcBA as a potential vector of multiple predicted T cell epitopes. This study evaluated the expression in vitro of the expression of a recombinant chimeric protein in the vector strain by analyzing the attenuation profile in macrophages and mice, and their protective efficacy against different virulent Brucella species. B. ovis abcBA strain was shown to be a promising vaccine vector, capable of expressing the recombinant chimeric protein and maintaining the attenuation profile. Therefore, the B. ovis abcBA PRB14 strain induced protection against the challenge with B. ovis, however, did not demonstrate protection against experimental challenge with B. abortus and B. suis. In order to evaluate the role of PRB14 in inducing a protective immune response against Brucella infection in BALB/c mice, we finally produced this chimeric protein in E. coli and used it as a vaccine antigen associated with Freud's adjuvant. However, this protein was not shown to be protective against B. abortus, B. ovis and B. suis infection in mice