Evaluation of the vaccine potential of recombinant proteins for protection against Salmonella enterica and the use of avian (Gallus gallus) cytokines as adjuvants and imunotherapics

Abstract

Currently, Salmonella enterica is one of the most important pathogens for the poultry industry due to growing concerns about food safety and public health. Brazil is the largest exporter in the world of chicken meat and the 2nd largest producer of food of poultry origin. Therefore, this activity has to meet many requirements involving the control of this pathogen. The control of Salmonella enterica infections in poultry, is done by biosecurity measures, antimicrobials and vaccines. However, a large number of antibiotic multidrug-resistant isolates has become disseminated in animal production environment and the antimicrobials used in food-producing animals have reduced or no action on these isolates. There are over 2,600 serotypes of Salmonella described, but live and inactivated vaccines available in Brazil are licensed to control only a few serovars (Salmonella gallinarum, Salmonella enteritidis and Salmonella typhimurium). Thus, this project proposes the evaluation of a "pool" of immunogenic proteins with high homology between serovars of the three major serogroups of Salmonella enterica (B, C and D), as a vaccine candidate for cross-protection against different serovars, relevant for poultry and public health. In addition, interleukin-12 (IL-12), Flagellin (FliC) and nanoparticles will be evaluated as adjuvant molecules of the inactivated subunit vaccine, to stimulate the cellular immune response. Considering the emergence of Salmonella enterica isolates multiresistant to antibiotics, this project also proposes the evaluation of CCL4 chemokine cloned from chickens, as an immunotherapic for the attraction of leukocytes to the intestinal mucosa and reduction of Salmonella enteritidis colonization. The chemoattractant property of this chemokine will be evaluated in vitro, in a chemotaxis assay. Later, the chemokine will be vectorized by an attenuated strain of Salmonella Typhimurium in the intestinal lumen of chickens to assess the attraction of phagocytes and lymphocytes and the control of Salmonella enteritidis after challenge. Thus, this research project aims to evaluate new measures to prevent and control non-typhoidal Salmonella enterica serovars, pathogens of difficult control and high relevance to public health. (AU)